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    • 专利摘要:
    The present invention provides a new class of 4,5-diaryl-3 ( 2H ) -furanone derivatives, which selectively strongly inhibit COX-2 over COX-1. These compounds are useful for treating inflammation, inflammation-related diseases and diseases mediated by COX-2.
    公开号:KR20010111584A
    申请号:KR1020017012902T
    申请日:2000-04-12
    公开日:2001-12-19
    发明作者:신송석；노민수；변영주；최진규；김진관；임경민；김지영；최영훈；하준용；이기화；모주현；정연수；정신；주영협；이창훈；강선화；박영호；이정범
    申请人:서경배；주식회사 태평양；
    IPC主号:
    专利说明:

    4,5-Diaryl-3 (2H) -furanone derivatives as cyclooxygenase-2 inhibitors} as cyclooxygenase-2 inhibitors
    [2] Prostaglandins are known to play an important role in inflammation. Prostaglandins are produced from arachidonic acid by cyclooxygenase and inhibit the synthesis of prostaglandins by cyclooxygenase, in particular the synthesis of PGE 2 , PGG 2 and PGH 2 to treat inflammation.
    [3] At least two types of cyclooxygenase, cyclooxygenase-1 (hereinafter abbreviated as "COX-1") and cyclooxygenase-2 (hereinafter abbreviated as "COX-2") are present. COX-1 is intrinsically present in the gastrointestinal tract and kidneys and is believed to maintain physiological homeostasis such as gastrointestinal integrity and kidney function. Inhibition of COX-1 activity can cause life-threatening toxicity, such as ulcers and bleeding in the gastrointestinal tract. COX-2, on the other hand, is induced by inflammatory stimuli and is known to advance inflammation. Therefore, selective inhibition of COX-2 on COX-1 is useful for the treatment of inflammation and the diseases associated with inflammation without causing gastrointestinal toxicity.
    [4] Conventional non-steroidal anti-inflammatory agents (NSAIDs), such as indomethacin, naproxen, ketoprofen, ibuprofen, piroxicam and diclofenac -steroidal anti-inflammatory drugs inhibit both COX-1 and COX-2, resulting in both anti-inflammatory and gastrointestinal toxicity. In addition, they have lethal gastrointestinal toxicities of bleeding and ulcers resulting from COX-1 inhibition, thus limiting their clinical use. Thus, COX-2 selective inhibitors can be used as anti-inflammatory agents that do not have gastrointestinal toxicities that frequently occur with long-term use of conventional NSAIDs.
    [5] COX-2 inhibitors are believed to have a broad therapeutic range, in addition to anti-inflammatory, analgesic and antipyretic effects. For example, inhibition of COX-2 can inhibit the development of certain types of cancer, particularly colorectal cancer [J. Clin. Invest. 100 , 1 (1997). COX-2 inhibitors may also be applied to the treatment of chronic degenerative neurological diseases such as Alzheimer's disease [Neurology 48 , 626 (1997)]. Inhibition of COX-2 is useful for reducing infarct volume associated with stroke [J. Neuroscience 17 , 2746 (1997).
    [6] Recently, two COX-2 selective anti-inflammatory drugs, celecoxib and rofecoxib, have been used to treat arthritis indications. Celecoxib and rofecoxib exhibit anti-inflammatory efficacy compared to conventional NSAIDs that do not have COX-2 selectivity. On the other hand, these drugs show significantly lower gastrointestinal toxicity compared to conventional NSAIDs that do not have a selectivity of COX-2 to COX-1. Therefore, selective inhibition of COX-2 alone may show sufficient anti-arthritis efficacy, and gastro-intestinal toxicity with respect to conventional NSAIDs that do not have COX-2 selectivity is particularly due to inhibition of COX-1.
    [7] cis -1,2- diaryl-alkene known as (cis -1,2-Diaryl-alkenes) or structural equivalents thereof are, drugs specific molecule stage (pharmacophore) that selectively inhibits the COX-2 relative to COX-1 is Ann. Rep. Med. Chem. 32 , 211 (1997). In the case of a celecoxib and rofecoxib, pyrazole (pyrazole) and 2 (5H) - corresponds to a pew ranon [2 (5H) -furanone] is the central structure (scaffold), respectively.
    [8]
    [9] Celecoxib rofecoxib
    [10] Appropriate central scaffolds for cis -alkene drug-specific molecular clusters, indicative of the method of administration, daily dosage, and clinical indications and safety profiles, both in vitro and in vivo. Inhibitor properties such as can be adjusted.
    [11] In the present invention, 3 ( 2H ) -furanone was used as the central skeleton for the COX-2 inhibitor. Although 3 ( 2H ) -furanone derivatives were prepared for the treatment of glaucoma, [EP 0737 476 A2], 3 ( 2H ) -furanone derivatives have never been used as COX-2 inhibitors. In addition, no reports have been reported for 4,5-diaryl-3 ( 2H ) -furanone derivatives.
    [12] The 4,5-diaryl-3 ( 2H ) -furanone derivatives disclosed herein selectively inhibit only COX-2 over COX-1 to mitigate the inflammatory effect. The 4,5-diaryl-3 ( 2H ) -furanone derivatives of the present invention show no actual inhibition on COX-1, resulting in a reduction in gastrointestinal side effects. Therefore, the 4,5-diaryl-3 ( 2H ) -furanone derivatives of the present invention are useful as anti-inflammatory substances with significantly reduced gastrointestinal side effects compared to conventional NSAIDs.
    [1] The present invention generally relates to 4,5-diaryl-3 ( 2H ) -furanone derivatives as selective cyclooxygenase-2 inhibitors, methods of making these derivatives, and for the treatment of inflammation and the treatment of inflammation-related diseases. It relates to the use of these derivatives.
    [791] 1 is a pharmacokinetics graph for Example 393 administered orally at 10 mg / kg body weight.
    [13] The present invention provides a new class of effective COX-2 selective inhibitors.
    [14] The present invention provides, as a COX-2 selective inhibitor, a new class of 3 ( 2H ) -furanone derivatives of formula (I) or pharmaceutically acceptable salts thereof:
    [15]
    [16] (One)
    [17] Food,
    [18] X is a halo, hydrido, or alkyl group;
    [19] Y is an alkylsulfonyl, aminosulfonyl, alkylsulfinyl, (N-acylamino) sulfonyl, (N-alkylamino) sulfonyl, or alkylthio group;
    [20] Z is oxygen or sulfur atom;
    [21] R 1 and R 2 are each independently selected from lower alkyl groups, or are linked together to the 2nd position carbon of the 3 ( 2H ) -furanone ring to form a 4- to 6-membered aliphatic- or hetero-ring; And AR is an aromatic group consisting of 5 to 10 atoms, optionally substituted.
    [22] The present invention further provides methods for the preparation of 3 ( 2H ) -furanone derivatives of formula (I).
    [23] A new class of 4,5-diaryl-3 ( 2H ) -furanone derivatives, or pharmaceutically acceptable salts thereof, useful for the treatment of inflammation and inflammation related diseases is defined by Formula (I):
    [24]
    [25] (One)
    [26] Food,
    [27] X is a halo, hydrido or alkyl group;
    [28] Y is an alkylsulfonyl, aminosulfonyl, alkylsulfinyl, (N-acylamino) sulfonyl, (N-alkylamino) sulfonyl or alkylthio group;
    [29] Z represents an oxygen or sulfur atom;
    [30] R 1 and R 2 are each independently selected from lower alkyl groups, or are linked together to the 2nd position carbon of the 3 ( 2H ) -furanone ring to form a 4- to 6-membered aliphatic- or hetero-ring; ; And AR is an aromatic group consisting of 5 to 10 atoms, optionally substituted.
    [31] The 4,5-diaryl-3 ( 2H ) -furanone derivatives of the present invention selectively inhibit COX-2 only against COX-1, resulting in reduced gastrointestinal toxicities compared to conventional NSAIDs, inflammation and It is useful for treating inflammation-related diseases.
    [32] Compounds of formula (I) are useful for the relief of inflammation, pain and fever, but are not limited thereto. For example, the compounds of formula (I) may be useful for treating pain and inflammation due to arthritis, including, but not limited to, rheumatoid arthritis, spondyloarthopathies Gout, osteoarthritis, systemic lupus erythematosus, and juvenile arthritis. Compounds of formula (I) may be usefully used for pain relief, including, but not limited to, headache, toothache, dysmenorrhea, neuralgia and pain symptoms such as neck or lumbar spine. Compounds of formula (I) may be usefully used to alleviate symptoms associated with viral infections, and the like, including but not limited to cold infections and influenza. Compounds of formula (I) may be used to treat inflammatory symptoms, including, but not limited to, myositis, gingivitis, synovitis, ankylosing spondylitis, Burstitis, burns, wounds, and the like. Compounds of formula (I) are useful for alleviating pain and inflammation after surgical and dental surgery. Such compounds are useful for treating psoriasis, eczema and dermatitis. Compounds of formula (I) may be useful for treating inflammatory symptoms accompanying a disease, including, but not limited to, inflammatory bowel disease, Crohn's disease, first Type I diabetes and the like. Such compounds are useful for inhibiting the growth of certain cyclooxygenase-mediated cancers, and include, but are not limited to, colorectal cancers. Compounds of formula (I) are useful for reducing the infarct site of reperfusion injury following stroke. Such compounds may be usefully used to alleviate inflammatory symptoms, and such inflammatory symptoms include, but are not limited to, asthma and bronchitis. Compounds of formula (I) are useful for treating degenerative neurological diseases, including Alzheimer's disease. Such compounds are useful in the treatment of retinopathy associated with diabetes and are involved in cyclooxygenase-mediated angiogenesis.
    [33] Due to the high COX-2 selectivity to COX-1, the compounds of formula (I) significantly reduce side effects of the gastrointestinal tract, such as ulcers and bleeding, compared to conventional NSAIDs. Thus, the compounds of formula (I) can be used as much safer substitutes than conventional NSAIDs. Compounds of formula (I) are useful in the treatment of humans as well as animals including, but not limited to, cattle, sheep, dogs, horses, and the like.
    [34] Compounds of formula (I) may be used in combination with other anti-inflammatory agents, including, but not limited to, conventional NSAIDs such as steroids, aspirin, acetaminophen, diclofenac, indomethacin, ibuprofen, and the like. Include. To compounds may be used in combination with a wide variety of therapeutic agents, those agents of the formula (I) include, but are not limited to, H 2 - antagonists (H 2 -antagonist), wherein such ACE inhibitor-hypertension agent or prostaglandin, wherein Immuno-modulators such as histamine, methotrexate, anti-coagulant and the like.
    [35] The compounds of formula (I) can be administered in a variety of ways, including, but not limited to, oral, intravenous, subcutaneous, topical administration, and the like. Compounds of formula (I) may be administered with pharmaceutically acceptable adjuvants, which include, but are not limited to, citric acid, hydrochloric acid, sodium chloride, tartaric acid, stearic acid, starch, gelatin, talc Sesame oil, ascorbic acid, olive oil, palm oil, methylcellulose, sodium carboxymethylcellulose, polyethylene glycol (PEG), polypropylene glycol, sweeteners, preservatives, ethanol, titanium oxide, sodium bicarbonate, soybean lecithin Include. The compounds of formula (I) may be prepared in various formulations, which include, but are not limited to, tablets, powders, granules, hard capsules, soft capsules, oral suspensions, inhalation sprays, injections, and the like. Include.
    [36] Compounds of formula (I) neutralize the compound with an appropriate pharmaceutically acceptable acid or base, such as potassium hydroxide, sodium hydroxide, hydrochloric acid, methanesulfonic acid, citric acid, etc., depending on the presence of a base or an acid group in the compound. By conversion to a pharmaceutically acceptable salt.
    [37] The compounds of formula (I) may be administered to humans in daily dosages of 0.1 to 100 mg / kg body weight, depending on the indication, condition or condition of the patient. However, the preferred daily dosage of the compound of formula (I) for inflammatory indications such as rheumatoid arthritis ranges from 0.1 to 10 mg / kg body weight. The compounds of formula (I) may be administered on various schedules, such as once daily, twice daily, three times daily, and the like, but are not limited to these schedules of administration.
    [38] Preferred classes of compounds include compounds of formula (I) or pharmaceutically acceptable salts thereof;
    [39] Food,
    [40] X is selected from halo, hydrido and lower alkyl;
    [41] Y is selected from (lower alkyl) sulfonyl, aminosulfonyl, (lower alkyl) sulfinyl, (lower N-acylamino) sulfonyl, (lower N-alkylamino) sulfonyl and (lower alkyl) thio;
    [42] Z is selected from oxygen and sulfur atoms;
    [43] R 1 and R 2 are independently selected from lower alkyl groups, or R 1 and R 2 are linked to the carbon number 2 of the 3 ( 2H ) -furanone ring to form a ring pentylidenyl (—CH 2) -CH 2 -CH 2 -CH 2- ), hexylidenyl (-CH 2 -CH 2 -CH 2 -CH 2 -CH 2- ), 4-tetrahydro- (4H) -pyranylidenyl (4 -tetrahydro- (4H) -Pyranylidenyl: -CH 2 -CH 2 -O-CH 2 -CH 2- ), 3-tetrahydrofuranylidenyl: -CH 2 -O-CH 2 -CH 2- ), Or 3-oxetanylidenyl (3-oxetanylidenyl: -CH 2 -O-CH 2- ); And AR is an aromatic group consisting of substituted or unsubstituted 5 to 10 atoms, selected from aromatic groups encompassing the following groups, but not limited to these aromatic groups;
    [44]
    [45] Wherein R 3 to R 7 , when present, are hydrido, halo, alkyl, haloalkyl, alkoxy, haloalkoxy, acyl, nitro, amino, N-alkylamino, N, N-dialkylamino, N-acyl Independently selected from amino, (haloacyl) amino, formyl, cyano, azido, hydroxy, alkylthio, alkylsulfonyl, phenyl, alkoxyalkyl and hydroxyalkyl, or adjacent two of R 3 to R 7 The groups are connected to each other to form methylenedioxy; And
    [46] R 8 to R 19 , when present, are each selected from hydrido, halo, alkyl, acyl, haloalkyl, alkoxy, formyl, cyano, nitro, amino, azido and N-acylamino.
    [47] Particularly preferred classes of compounds include compounds of formula (I) or pharmaceutically acceptable salts thereof;
    [48] Food,
    [49] X is selected from fluoro, chloro, bromo, hydrido, methyl, ethyl and n-propyl;
    [50] Y is methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, aminosulfonyl, methylsulfinyl, ethylsulfinyl, n-propylsulfinyl, (N-acetylamino) sulfonyl, (N-propionylamino) Sulfonyl, (N-butyrylamino) sulfonyl, (N-methylamino) sulfonyl, (N-ethylamino) sulfonyl, methylthio, ethylthio and n-propylthio;
    [51] Z is selected from oxygen and sulfur atoms;
    [52] R 1 and R 2 are independently selected from methyl and ethyl, or R 1 and R 2 are pentyldenyl (—CH 2 −) linked together to carbon 2 of the 3 ( 2H ) -furanone ring to form a ring; CH 2 -CH 2 -CH 2- ), hexylideneyl (-CH 2 -CH 2 -CH 2 -CH 2 -CH 2- ), 4-tetrahydro- (4H) -pyranylidenyl (-CH 2- CH 2 -O-CH 2 -CH 2- ), 3-tetrahydrofuranylideneyl (-CH 2 -O-CH 2 -CH 2- ) and 3-oxetanylideneyl (-CH 2 -O-CH 2 -);
    [53] R 3 to R 7 , when present, are respectively hydrido, fluoro, chloro, bromo, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, n-pentyl, isopentyl , Fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 1-fluoroethyl, 2,2-difluoroethyl, 1,2-difluoroethyl, 1,1-di Fluoroethyl, 2,2,2-trifluoroethyl, methoxy, ethoxy, n-propyloxy, isopropyloxy, n-butoxy, trifluoromethoxy, difluoromethoxy, fluoromethoxy, acetyl , Propionyl, n-butanoyl, isobutanoyl, n-pentanoyl, nitro, amino, N-methylamino, N-ethylamino, Nn-propylamino, N, N-dimethylamino, N-acetylamino, N Propionylamino, N- (trifluoroacetyl) amino, formyl, hydroxy, methylthio, ethylthio, n-propylthio, methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, phenyl, hydroxy Butyl, 1-hydroxyethyl and 2-hydroxypropyl independently selected from hydroxy ethyl, or R 3 to R 7 in the two groups are connected to each other adjacent to form a methylenedioxy; And R 8 to R 19 , when present, are respectively hydrido, fluoro, chloro, bromo, methyl, ethyl, n-propyl, isopropyl, acetyl, propionyl, methoxy, ethoxy, isopropyloxy, independently from n-propyloxy and formyl.
    [54] Most preferred subfamily compounds in formula (I) are the compounds of formula (II) or pharmaceutically acceptable salts thereof;
    [55]
    [56] (Ⅱ)
    [57] Food,
    [58] Y is alkylsulfonyl, aminosulfonyl, alkylsulfinyl, (N-acylamino) sulfonyl, (N-alkylamino) sulfonyl or alkylthio;
    [59] Z is oxygen or sulfur atom;
    [60] R 1 and R 2 are independently selected from lower alkyl groups; And,
    [61] R 3 to R 7 , when present, are respectively hydrido, halo, alkyl, haloalkyl, alkoxy, haloalkoxy, acyl, nitro, amino, N-alkylamino, N, N-dialkylamino, N-acylamino, Independently selected from N- (haloacyl) amino, formyl, cyano, azido, hydroxy, alkylthio, alkylsulfonyl, phenyl, alkoxyalkyl and hydroxyalkyl, or adjacent two of R 3 to R 7 The groups are connected to each other to form methylenedioxy.
    [62] Preferred classes of compounds include compounds of formula (II) or pharmaceutically acceptable salts thereof;
    [63] Food,
    [64] Y is selected from (lower alkyl) sulfonyl, aminosulfonyl, (lower alkyl) sulfinyl, (lower N-acylamino) sulfonyl, (lower N-alkylamino) sulfonyl, and (lower alkyl) thio;
    [65] Z is selected from oxygen and sulfur atoms;
    [66] R 1 and R 2 are independently selected from methyl and ethyl groups; And,
    [67] R 3 to R 7 , when present, are respectively hydrido, halo, lower alkyl, lower haloalkyl, lower alkoxy, lower haloalkoxy, lower acyl, nitro, amino, lower N-alkylamino, lower N, N-dialkyl Independently selected from amino, lower N-acylamino, (lower haloacyl) amino, formyl, cyano, azido, hydroxy, lower alkylthio, lower alkylsulfonyl, phenyl, lower alkoxyalkyl and lower hydroxyalkyl Or two adjacent groups in R 3 to R 7 are connected to each other to form methylenedioxy.
    [68] Particularly preferred classes of compounds include compounds of formula (II) or pharmaceutically acceptable salts thereof;
    [69] Food,
    [70] Y is methylsulfonyl, aminosulfonyl, methylsulfinyl, (N-acetylamino) sulfonyl, (N-propionylamino) sulfonyl, (N-butyrylamino) sulfonyl, (N-methylamino) sul Selected from among poly, (N-ethylamino) sulfonyl and methylthio;
    [71] Z is selected from oxygen and sulfur atoms;
    [72] R 1 and R 2 are independently selected from methyl and ethyl groups; And,
    [73] R 3 to R 7 , when present, are respectively hydrido, fluoro, chloro, bromo, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, n-pentyl, isopentyl , Fluoromethyl, difluoromethyl, trifluoromethyl, 1-fluoroethyl, 2,2,2-trifluoroethyl, methoxy, trifluoromethoxy, difluoromethoxy, fluoromethoxy, acetyl , Propionyl, n-butanoyl, isobutanoyl, n-pentanoyl, nitro, amino, N, N-dimethylamino, N-acetylamino, N-propionylamino, formyl, hydroxy, methylthio, ethyl Independently selected from thio, n-propylthio, methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, phenyl, hydroxymethyl, 1-hydroxyethyl and 2-hydroxyethyl, or R 3 to R 7 Two adjacent groups in the group are connected to each other to form methylenedioxy.
    [74] expression Particularly preferred groups of compounds in (II) include the following compounds and pharmaceutically acceptable salts thereof:
    [75] 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4-phenyl-3 ( 2H ) -furanone;
    [76] 2,2-dimethyl-4- (2-fluorophenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [77] 2,2-dimethyl-4- (3-fluorophenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [78] 2,2-dimethyl-4- (4-fluorophenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [79] 2,2-dimethyl-4- (3-fluoro-4-phenylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [80] 4- (2,4-difluorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [81] 4- (2,5-difluorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [82] 4- (3,4-difluorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [83] 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [84] 4- (2-chlorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [85] 4- (3-chlorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [86] 4- (4-chlorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [87] 4- (3-chloro-4-fluorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [88] 4- (3-chloro-5-fluorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [89] 4- (4-chloro-3-fluorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [90] 4- (2,4-dichlorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [91] 4- (3,4-dichlorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [92] 4- (3,5-dichlorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [93] 4- (4-bromophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [94] 4- (3-bromophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [95] 2,2-dimethyl-4- (2-methylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [96] 2,2-dimethyl-4- (3-methylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [97] 2,2-dimethyl-4- (4-methylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [98] 2,2-dimethyl-4- (4-ethylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [99] 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (4-n-propylphenyl) -3 ( 2H ) -furanone;
    [100] 2,2-dimethyl-4- (3-isopropylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [101] 2,2-dimethyl-4- (4-isopropylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [102] 2,2-dimethyl-4- (3-fluoro-4-isopropylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [103] 4- (3-chloro-4-isopropylphenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [104] 2,2-dimethyl-4- (4-n-butylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [105] 2,2-dimethyl-4- (4-t-butylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [106] 2,2-dimethyl-4- (4-fluoro-2-methylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [107] 2,2-dimethyl-4- (5-fluoro-2-methylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [108] 2,2-dimethyl-4- (3-fluoro-4-methylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [109] 2,2-dimethyl-4- (2-methoxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [110] 2,2-dimethyl-4- (3-methoxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [111] 2,2-dimethyl-4- (4-methoxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [112] 2,2-dimethyl-4- (2-hydroxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [113] 2,2-dimethyl-4- (3-hydroxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [114] 2,2-dimethyl-4- (4-hydroxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [115] 4- (2,4-dimethoxyphenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [116] 4- (3,4-dimethoxyphenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [117] 2,2-dimethyl-4- (3,4-methylenedioxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [118] 2,2-dimethyl-4- (3,5-dimethyl-4-methoxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [119] 2,2-dimethyl-4- (3,4-dimethylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [120] 2,2-dimethyl-4- (3-fluoro-4-methoxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [121] 2,2-dimethyl-4- (3-fluoro-4-hydroxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [122] 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- {4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    [123] 2,2-dimethyl-4- {4- (ethylthio) phenyl} -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [124] 2,2-dimethyl-4,5-di- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [125] 2,2-dimethyl-4- {4- (ethylsulfonyl) phenyl} -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [126] 2,2-dimethyl-4- {3- (fluoromethyl) phenyl} -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [127] 2,2-dimethyl-4- {4- (fluoromethyl) phenyl} -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [128] 4- {3- (difluoromethyl) phenyl} -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [129] 4- {4- (difluoromethyl) phenyl} -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [130] 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- {2- (trifluoromethyl) phenyl} -3 ( 2H ) -furanone;
    [131] 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- {3- (trifluoromethyl) phenyl} -3 ( 2H ) -furanone;
    [132] 2,2-dimethyl-4- {3-fluoro-5- (trifluoromethyl) phenyl} -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [133] 4- {3-chloro-5- (trifluoromethyl) phenyl} -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [134] 4- {4-acetyl-3- (trifluoromethyl) phenyl} -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [135] 4- {3-acetyl-5- (trifluoromethyl) phenyl} -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [136] 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- {4- (trifluoromethyl) phenyl} -3 ( 2H ) -furanone;
    [137] 2,2-dimethyl-4- {3,5-di- (trifluoromethyl) phenyl} -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [138] 4- {4-chloro-3- (trifluoromethyl) phenyl} -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [139] 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (3-nitrophenyl) -3 ( 2H ) -furanone;
    [140] 4- (3-aminophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [141] 2,2-dimethyl-4- {4- (N, N-dimethylamino) phenyl} -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [142] 2,2-dimethyl-4- (2-formylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [143] 2,2-dimethyl-4- (3-formylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [144] 2,2-dimethyl-4- (4-formylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [145] 4- {3- (acetylamino) phenyl} -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [146] 4- (3-acetylphenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [147] 4- (4-acetylphenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [148] 4- (4-biphenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [149] 2,2-dimethyl-4- [4- (1-hydroxyethyl) phenyl] -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [150] 2,2-dimethyl-4- [4- (1-hydroxymethyl) phenyl] -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [151] 2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -4-phenyl-3 ( 2H ) -furanone;
    [152] 2,2-dimethyl-4- (3-fluorophenyl) -5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [153] 2,2-dimethyl-4- (4-fluorophenyl) -5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [154] 2,2-dimethyl-4- (3,5-difluorophenyl) -5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [155] 4- (3-chloro-4-fluorophenyl) -2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [156] 4- (3-chloro-5-fluorophenyl) -2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [157] 4- (3-chlorophenyl) -2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [158] 4- (4-t-butylphenyl) -2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [159] 2,2-dimethyl-4- (2-fluorophenyl) -5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [160] 2,2-dimethyl-4- (3-fluorophenyl) -5- {4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    [161] 2,2-dimethyl-5- {4- (methylthio) phenyl} -4-phenyl-3 ( 2H ) -furanone;
    [162] 4- (3-chlorophenyl) -2,2-dimethyl-5- {4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    [163] 2,2-dimethyl-5- {4- (methylthio) phenyl} -4- {3- (trifluoromethyl) phenyl} -3 ( 2H ) -furanone;
    [164] 2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -4- {3- (trifluoromethyl) phenyl} -3 ( 2H ) -furanone;
    [165] 2,2-dimethyl-4- {3-fluoro-5- (trifluoromethyl) phenyl} -5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [166] 4- {3-chloro-5- (trifluoromethyl) phenyl} -2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [167] 4- {3-acetyl-5- (trifluoromethyl) phenyl} -2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [168] 4- {4-acetyl-3- (trifluoromethyl) phenyl} -2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [169] 2,2-dimethyl-5- {4- (methylthio) phenyl} -4- (4-nitrophenyl) -3 ( 2H ) -furanone;
    [170] 2,2-dimethyl-4- (4-methoxyphenyl) -5- {4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    [171] 4- (2,5-difluorophenyl) -2,2-dimethyl-5- {4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    [172] 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    [173] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    [174] 5- {4- (aminosulfonyl) phenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [175] 5- {4- (aminosulfonyl) phenyl} -4- (3-chloro-5-fluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [176] 5- {4- (aminosulfonyl) phenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [177] 5- {4- (aminosulfonyl) phenyl} -4- (3,4-dichlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [178] 5- {4- (aminosulfonyl) phenyl} -4- (3,5-dichlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [179] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {3- (trifluoromethyl) phenyl} -3 ( 2H ) -furanone;
    [180] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {3-fluoro-5- (trifluoromethyl) phenyl} -3 ( 2H ) -furanone;
    [181] 5- {4- (aminosulfonyl) phenyl} -4- {3-chloro-5- (trifluoromethyl) phenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    [182] 4- {3-acetyl-5- (trifluoromethyl) phenyl} -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    [183] 4- {4-acetyl-5- (trifluoromethyl) phenyl} -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    [184] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (3-methylphenyl) -3 ( 2H ) -furanone;
    [185] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    [186] 5- {4- (aminosulfonyl) phenyl} -4- (2,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [187] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (3,4-dimethylphenyl) -3 ( 2H ) -furanone;
    [188] 5- {4- (aminosulfonyl) phenyl} -4- (2,4-dimethoxyphenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [189] 5- {4- (aminosulfonyl) phenyl} -4- (3,4-dimethoxyphenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [190] 4- (3-acetylphenyl) -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    [191] 4- (3-acetyl-5-chlorophenyl) -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    [192] 4- (3-acetyl-4-chlorophenyl) -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    [193] 4- (3-acetyl-4-fluorophenyl) -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    [194] 4- (3-acetyl-5-fluorophenyl) -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    [195] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    [196] 5- {4- (aminosulfonyl) phenyl} -4- (3-chloro-4-fluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [197] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (3-methoxyphenyl) -3 ( 2H ) -furanone;
    [198] 4- (4-acetylphenyl) -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    [199] 4- (4-acetyl-3-chlorophenyl) -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    [200] 4- (4-acetyl-3-fluorophenyl) -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    [201] 4- (4-acetyl-3-bromophenyl) -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    [202] 4- {4- (acetylamino) phenyl} -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    [203] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (2-methylphenyl) -3 ( 2H ) -furanone;
    [204] 5- {4- (aminosulfonyl) phenyl} -4- (3,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [205] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (4-methylphenyl) -3 ( 2H ) -furanone;
    [206] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {3,4- (methylenedioxy) phenyl} -3 ( 2H ) -furanone;
    [207] 5- {4- (aminosulfonyl) phenyl} -4- (4-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [208] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    [209] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (3-fluoro-4-phenylphenyl) -3 ( 2H ) -furanone;
    [210] 5- {4- (aminosulfonyl) phenyl} -4- (4-bromophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [211] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (5-isopropyl-2-methoxyphenyl) -3 ( 2H ) -furanone;
    [212] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (5-isopropylphenyl) -3 ( 2H ) -furanone;
    [213] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {4- (ethylthio) phenyl} -3 ( 2H ) -furanone;
    [214] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (2-methoxyphenyl) -3 ( 2H ) -furanone;
    [215] 5- {4- (aminosulfonyl) phenyl} -4- (4-n-butylphenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [216] 5- {4- (aminosulfonyl) phenyl} -4- (3,5-dichlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [217] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (3,4,5-trimethoxyphenyl) -3 ( 2H ) -furanone;
    [218] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (4-hydroxyphenyl) -3 ( 2H ) -furanone;
    [219] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (4-fluoro-3-methoxyphenyl) -3 ( 2H ) -furanone;
    [220] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (3,5-dimethyl-4-methoxyphenyl) -3 ( 2H ) -furanone;
    [221] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (4-ethylphenyl) -3 ( 2H ) -furanone;
    [222] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (3-phenylphenyl) -3 ( 2H ) -furanone;
    [223] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (2-fluorophenyl) -3 ( 2H ) -furanone;
    [224] 4- (3-aminophenyl) -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    [225] 5- {4- (aminosulfonyl) phenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [226] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (3-nitrophenyl) -3 ( 2H ) -furanone;
    [227] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (5-fluoro-2-methylphenyl) -3 ( 2H ) -furanone;
    [228] 2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4-phenyl-3 ( 2H ) -furanone;
    [229] 2-ethyl-4- (4-fluorophenyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [230] 2-ethyl-4- (3-fluorophenyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [231] 4- (3-chlorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [232] 2-ethyl-4- (2-fluorophenyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [233] 4- (4-acetylphenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [234] 4- (4-acetyl-3-chlorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [235] 4- (4-acetyl-3-fluorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [236] 4- {4-acetyl-3- (trifluoromethyl) phenyl} -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [237] 4- (3,5-difluorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [238] 4- (3,4-difluorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [239] 4- (3-chloro-4-fluorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [240] 4- (3-chloro-5-fluorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [241] 4- (3,5-dichlorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [242] 2-ethyl-4- (4-methoxyphenyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [243] 2-ethyl-2-methyl-4- (4-methylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [244] 2-ethyl-2-methyl-4- (3-methylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [245] 2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    [246] 4- (3-acetylphenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [247] 4- (3-acetyl-4-fluorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [248] 4- (3-acetyl-4-fluorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [249] 4- {3- (acetylamino) phenyl} -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [250] 2-ethyl-2-methyl-4- {3,4- (methylenedioxy) phenyl} -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [251] 4- {4-Chloro-3- (trifluoromethyl) phenyl} -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [252] 4- {5-chloro-3- (trifluoromethyl) phenyl} -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [253] 2-ethyl-4- {5-fluoro-3- (trifluoromethyl) phenyl} -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -fu Lanone;
    [254] 2-ethyl-4- (4-ethylphenyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [255] 2-ethyl-4- (3-methoxyphenyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [256] 2-ethyl-4- (3-isopropylphenyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [257] 2-ethyl-4- (4-isopropylphenyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [258] 2-ethyl-4- (3-fluoro-4-isopropylphenyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [259] 2-ethyl-4- (5-fluoro-4-isopropylphenyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [260] 4- (3-chloro-4-isopropylphenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [261] 4- (4-t-butylphenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [262] 2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- (4-n-propylphenyl) -3 ( 2H ) -furanone;
    [263] 4- (4-n-butylphenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [264] 4- (3,4-dimethylphenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [265] 4- (3,4-dichlorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [266] 4- (3-aminophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [267] 4- {3- (difluoromethyl) phenyl} -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [268] 2-ethyl-4- {4- (fluoromethyl) phenyl} -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [269] 4- (4-chlorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [270] 2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- {4- (trifluoromethyl) phenyl} -3 ( 2H ) -furanone;
    [271] 2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- {4- (trifluoromethoxy) phenyl} -3 ( 2H ) -furanone;
    [272] 4- (4-chloro-3-fluorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [273] 2-ethyl-4- (4-fluoro-2-methylphenyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [274] 2-ethyl-4- (5-fluoro-2-methylphenyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [275] 4- (3,4-dimethoxyphenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [276] 4- (3,5-dimethoxyphenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [277] 2-ethyl-4- (5-fluoro-2-methylphenyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [278] 2-ethyl-4- (3-fluoro-4-methoxyphenyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [279] 4- (3,5-difluorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [280] 4- (3,5-dichlorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [281] 4- (3,5-dimethyl-4-methoxyphenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [282] 2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- (3,4,5-trimethoxyphenyl) -3 ( 2H ) -furanone;
    [283] 5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-4-phenyl-3 ( 2H ) -furanone;
    [284] 5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- (4-fluorophenyl) -2-methyl-3 ( 2H ) -furanone;
    [285] 5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- (3-fluorophenyl) -2-methyl-3 ( 2H ) -furanone;
    [286] 5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-4- (3-methylphenyl) -3 ( 2H ) -furanone;
    [287] 5- {4- (aminosulfonyl) phenyl} -4- (3-chlorophenyl) -2-ethyl-2-methyl-3 ( 2H ) -furanone;
    [288] 5- {4- (aminosulfonyl) phenyl} -4- (4-chlorophenyl) -2-ethyl-2-methyl-3 ( 2H ) -furanone;
    [289] 5- (4-aminosulfonylphenyl) -2-ethyl-2-methyl-4- {3- (trifluoromethyl) phenyl} -3 ( 2H ) -furanone;
    [290] 5- (4-aminosulfonylphenyl) -2-ethyl-2-methyl-4- {3-fluoro-5- (trifluoromethyl) phenyl} -3 ( 2H ) -furanone;
    [291] 5- (4-aminosulfonylphenyl)-{3-chloro-5- (trifluoromethyl) phenyl} -2-ethyl-2-methyl-4-3 ( 2H ) -furanone;
    [292] 5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-4- {4- (trifluoromethyl) phenyl} -3 ( 2H ) -furanone;
    [293] 5- {4- (aminosulfonyl) phenyl} -4- (3,5-difluorophenyl) -2-ethyl-2-methyl-3 ( 2H ) -furanone;
    [294] 5- {4- (aminosulfonyl) phenyl} -4- (3,5-dichlorophenyl) -2-ethyl-2-methyl-3 ( 2H ) -furanone;
    [295] 5- {4- (aminosulfonyl) phenyl} -4- (3,4-difluorophenyl) -2-ethyl-2-methyl-3 ( 2H ) -furanone;
    [296] 5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- (3-methoxyphenyl) -2-methyl-3 ( 2H ) -furanone;
    [297] 4- (4-acetylphenyl) -5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-3 ( 2H ) -furanone;
    [298] 4- (4-acetyl-3-chlorophenyl) -5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-3 ( 2H ) -furanone;
    [299] 4- (4-acetyl-3-fluorophenyl) -5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-3 ( 2H ) -furanone;
    [300] 4- {4-acetyl-4- (trifluoromethyl) phenyl} -5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-3 ( 2H ) -furanone;
    [301] 5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- (4-fluoro-3-methoxyphenyl) -2-methyl-3 ( 2H ) -furanone;
    [302] 2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -4-phenyl-3 ( 2H ) -furanone;
    [303] 2,2-diethyl-4- (3-fluorophenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [304] 4- (3-chlorophenyl) -2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [305] 2,2-diethyl-4- (3-methylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [306] 2,2-diethyl-4- (3-methoxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [307] 2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -4- {3- (trifluoromethyl) phenyl} -3 ( 2H ) -furanone;
    [308] 2,2-diethyl-4- {3-fluoro-5- (trifluoromethyl) phenyl} -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [309] 4- {3-chloro-5- (trifluoromethyl) phenyl} -2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [310] 2,2-diethyl-4- (4-fluorophenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [311] 4- (4-chlorophenyl) -2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [312] 2,2-diethyl-4- (4-methylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [313] 2,2-diethyl-4- (4-methoxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [314] 2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -4- {4- (trifluoromethyl) phenyl} -3 ( 2H ) -furanone;
    [315] 4- (4-acetyl-3-chlorophenyl) -2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [316] 4- (4-acetylphenyl) -2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [317] 4- (4-acetyl-3-fluorophenyl) -2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [318] 4- (4-acetyl-2-chlorophenyl) -2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [319] 4- (4-acetyl-2-fluorophenyl) -2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [320] 2,2-diethyl-4- (3,4-difluorophenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [321] 2,2-diethyl-4- (3,5-difluorophenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [322] 2,2-diethyl-4- (2,5-difluorophenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [323] 4- (3-chloro-5-fluorophenyl) -2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [324] 2,2-diethyl-4- (3,4-dimethoxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [325] 2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -4- (4-n-propylphenyl) -3 ( 2H ) -furanone;
    [326] 2,2-diethyl-4- (2,4-difluorophenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [327] 4- (4-t-butylphenyl) -2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [328] 2,2-diethyl-4- (3,4-dimethylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [329] 2,2-diethyl-4- (4-isopropylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [330] 4- (3-acetylphenyl) -2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [331] 4- (3-chloro-4-fluorophenyl) -2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [332] 2,2-diethyl-4- (3-fluoro-4-methoxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [333] 4- (3-chloro-4-fluorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl}-( 2H ) -furan-3-thione;
    [334] 2,2-dimethyl-4- (4-fluorophenyl) -5- {4- (methylsulfonyl) phenyl}-( 2H ) -furan-3-thione;
    [335] 2,2-dimethyl-4- (3-fluorophenyl) -5- {4- (methylsulfonyl) phenyl}-( 2H ) -furan-3-thione;
    [336] 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl}-( 2H ) -furan-3-thione;
    [337] 5- [4-{(acetylamino) sulfonyl} phenyl] -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    [338] 5- [4-{(butyrylamino) sulfonyl} phenyl] -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    [339] 2,2-dimethyl-5- [4-{(N-methylamino) sulfonyl} phenyl] -4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    [340] 2,2-dimethyl-5- [4-{(N-ethylamino) sulfonyl} phenyl] -4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    [341] Formula (I) includes the most preferred sub-series compounds of Formula (III) or pharmaceutically acceptable salts thereof;
    [342]
    [343] (Ⅲ)
    [344] Food,
    [345] Y is N-alkylsulfonyl, aminosulfonyl, alkylsulfinyl, (N-acylamino) sulfonyl, (N-alkylamino) sulfonyl or alkylthio;
    [346] Z is oxygen or sulfur atom;
    [347] m and n are integers of 1 to 3 and satisfy the condition of (m + n) < 4;
    [348] P is selected from an oxygen atom and a methylene group (-CH 2- ); And,
    [349] R 3 to R 7 , when present, are respectively hydrido, halo, alkyl, haloalkyl, alkoxy, haloalkoxy, acyl, nitro, amino, N-alkylamino, N, N-dialkylamino, N-acylamino, Independently selected from N- (haloacyl) amino, formyl, cyano, azido, hydroxy, alkylthio, alkylsulfonyl, phenyl, alkoxyalkyl and hydroxyalkyl, or adjacent two of R 3 to R 7 The groups are connected to each other to form methylenedioxy.
    [350] Preferred classes of compounds are Compounds of (III) or pharmaceutically acceptable salts thereof;
    [351] Food,
    [352] Y is selected from (lower alkyl) sulfonyl, aminosulfonyl, (lower alkyl) sulfinyl, (lower N-acylamino) sulfonyl, (lower N-alkylamino) sulfonyl and (lower alkyl) thio;
    [353] Z is selected from oxygen and sulfur atoms;
    [354] m and n are integers from 1 to 3 and satisfy the condition (m + n) < 4;
    [355] P is selected from an oxygen atom and a methylene group (-CH 2- ); And,
    [356] R 3 to R 7, in the presence of hydrido, halo, alkyl, haloalkyl, alkoxy, haloalkoxy, acyl, nitro, amino, N-alkylamino, N, N-dialkylamino, N-acylamino, Independently selected from N- (haloacyl) amino, formyl, cyano, azido, hydroxy, alkylthio, alkylsulfonyl, phenyl, lower alkoxyalkyl and lower hydroxyalkyl, or in R 3 to R 7 Two adjacent groups are connected to each other to form methylenedioxy.
    [357] Particularly preferred classes of compounds include compounds of formula (III) or pharmaceutically acceptable salts thereof;
    [358] Food,
    [359] Y is methylsulfonyl, aminosulfonyl, methylsulfinyl, (N-acetylamino) sulfonyl, (N-propionylamino) sulfonyl, (N-butyrylamino) sulfonyl, (N-methylamino) sul Is selected from among poly, (N-ethylamino) sulfonyl and methylthio;
    [360] Z is selected from oxygen and sulfur atoms;
    [361] m and n are integers of 1 to 3 and satisfy the condition (m + n) < 4;
    [362] P is an oxygen atom or a methylene group (-CH 2- ); And,
    [363] R 3 to R 7 , when present, are independent from hydrido, fluoro, chloro, bromo, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, acetyl and propionyl, respectively Is selected.
    [364] Particularly preferred groups of compounds in formula (III) include the following compounds and pharmaceutically acceptable salts thereof:
    [365] 2- {4- (methylsulfonyl) phenyl} -3-phenyl-1-oxa-spiro [4,4] non-2-en-4-one;
    [366] 3- (3-methylphenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one;
    [367] 3- (4-isopropylphenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one;
    [368] 3- (3,5-difluorophenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one;
    [369] 3- (2-fluorophenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one;
    [370] 3- (3-fluorophenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one;
    [371] 3- (3-chlorophenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one;
    [372] 3- (4-fluorophenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one;
    [373] 3- (4-acetylphenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one;
    [374] 3- (4-acetyl-3-fluorophenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one;
    [375] 3- (4-acetyl-3-chlorophenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one;
    [376] 2- {4- (methylsulfonyl) phenyl} -3-phenyl-1-oxa-spiro [4,5] dec-2-en-4-one;
    [377] 2- {4- (methylsulfonyl) phenyl} -3- {3- (trifluoromethyl) phenyl} -1-oxa-spiro [4,5] dec-2-en-4-one;
    [378] 3- (3-methylphenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,5] dec-2-en-4-one;
    [379] 3- (4-acetylphenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,5] dec-2-en-4-one;
    [380] 3- (3-fluorophenyl) -2- {4- (methylsulfonyl) phenyl} -1,8-dioxa-spiro [4,5] dec-2-en-4-one;
    [381] 3- (3,5-difluorophenyl) -2- {4- (methylsulfonyl) phenyl} -1,8-dioxa-spiro [4,5] dec-2-en-4-one;
    [382] 3- (3-chlorophenyl) -2- {4- (methylsulfonyl) phenyl} -1,8-dioxa-spiro [4,5] dec-2-en-4-one;
    [383] 3- (4-acetylphenyl) -2- {4- (methylsulfonyl) phenyl} -1,8-dioxa-spiro [4,5] dec-2-en-4-one;
    [384] 2- {4- (methylsulfonyl) phenyl} -3-phenyl-1,8-dioxa-spiro [4,5] dec-2-en-4-one;
    [385] 3- (3-chlorophenyl) -2- {4- (methylsulfonyl) phenyl} -1,8-dioxa-spiro [4,5] dec-2-en-4-one;
    [386] In formula (I), there are the most preferred sub-series compounds of formula (IV) or pharmaceutically acceptable salts thereof;
    [387]
    [388] (Ⅳ)
    [389] Food,
    [390] X is halo or alkyl;
    [391] Y is alkylsulfonyl, aminosulfonyl, alkylsulfinyl, (N-acylamino) sulfonyl, (N-alkylamino) sulfonyl or alkylthio;
    [392] Z is oxygen or sulfur atom; And R 3 to R 7 , when present, are each independently selected from hydrido, halo, alkyl, haloalkyl, alkyloxy, nitro, amino, N-acylamino, acyl, formyl, hydroxyalkyl, phenyl and cyano Or two adjacent groups in R 3 to R 7 are connected to each other to form methylenedioxy.
    [393] Preferred classes of compounds include compounds of formula (IV) or pharmaceutically acceptable salts thereof,
    [394] Food,
    [395] X is halo or lower alkyl;
    [396] Y is selected from (lower alkyl) sulfonyl, aminosulfonyl, (lower alkyl) sulfinyl, (lower N-acylamino) sulfonyl, (lower N-alkylamino) sulfonyl and (lower alkyl) thio;
    [397] Z is selected from oxygen and sulfur atoms; And R 3 to R 7 , when present, are independently selected from hydrido, halo, lower alkyl, lower haloalkyl, lower alkyloxy, nitro, amino and N- (lower acyl) amino, respectively.
    [398] Particularly preferred classes of compounds include compounds of formula (IV) or pharmaceutically acceptable salts thereof;
    [399] Food,
    [400] X is fluoro, chloro, bromo or methyl;
    [401] Y is methylsulfonyl, ethylsulfonyl, aminosulfonyl, methylsulfinyl, ethylsulfinyl, (N-acetylamino) sulfonyl, (N-propionylamino) sulfonyl, (N-butyrylamino) sulfonyl , (N-methylamino) sulfonyl, (N-ethylamino) sulfonyl, methylthio and ethylthio;
    [402] Z is selected from oxygen and sulfur atoms; And when R 3 to R 7 are present, respectively, hydrido, fluoro, chloro, bromo, methyl, ethyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy , n-propyloxy, isopropyloxy, n-butoxy, nitro, amino, N-acetylamino and N-propionylamino.
    [403] Particularly preferred groups of specific compounds in formula (IV) include the following compounds and pharmaceutically acceptable salts thereof:
    [404] 2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -4-phenyl-3 ( 2H ) -furanone;
    [405] 2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -4-phenyl-3 ( 2H ) -furanone;
    [406] 2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -4-phenyl-3 ( 2H ) -furanone;
    [407] 5- {4- (aminosulfonyl) -3-fluorophenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    [408] 4- (2-chlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    [409] 4- (2-chlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [410] 4- (2-chlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [411] 5- {4- (aminosulfonyl) -3-fluorophenyl} -4- (2-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [412] 4- (3-chlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    [413] 4- (3-chlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [414] 4- (3-chlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [415] 5- {4- (aminosulfonyl) -3-fluorophenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [416] 4- (4-chlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    [417] 4- (4-chlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [418] 4- (4-chlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [419] 5- {4- (aminosulfonyl) -3-fluorophenyl} -4- (4-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [420] 4- (3,4-dichlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    [421] 4- (3,4-dichlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [422] 4- (3,4-dichlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [423] 5- {4- (aminosulfonyl) -3-fluorophenyl} -4- (3,4-dichlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [424] 2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -4- (2-fluorophenyl) -3 ( 2H ) -furanone;
    [425] 2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -4- (2-fluorophenyl) -3 ( 2H ) -furanone;
    [426] 2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -4- (2-fluorophenyl) -3 ( 2H ) -furanone;
    [427] 5- {4- (aminosulfonyl) -3-fluorophenyl} -2,2-dimethyl-4- (2-fluorophenyl) -3 ( 2H ) -furanone;
    [428] 2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    [429] 2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    [430] 2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    [431] 5- {4- (aminosulfonyl) -3-fluorophenyl} -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    [432] 2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    [433] 2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    [434] 2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    [435] 5- {4- (aminosulfonyl) -3-fluorophenyl} -2,2-dimethyl-4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    [436] 4- (2,4-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    [437] 4- (2,4-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [438] 4- (2,4-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [439] 5- {4- (aminosulfonyl) -3-fluorophenyl} -4- (2,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [440] 4- (2,5-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    [441] 4- (2,5-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [442] 4- (2,5-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [443] 5- {4- (aminosulfonyl) -3-fluorophenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [444] 4- (2,6-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    [445] 4- (2,6-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [446] 4- (2,6-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [447] 5- {4- (aminosulfonyl) -3-fluorophenyl} -4- (2,6-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [448] 4- (3,4-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    [449] 4- (3,4-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [450] 4- (3,4-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [451] 5- {4- (aminosulfonyl) -3-fluorophenyl} -4- (3,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [452] 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    [453] 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [454] 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [455] 5- {4- (aminosulfonyl) -3-fluorophenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [456] 2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -4- (2-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    [457] 2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -4- (2-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    [458] 2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -4- (2-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    [459] 5- {4- (aminosulfonyl) -3-fluorophenyl} -2,2-dimethyl-4- (2-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    [460] 2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    [461] 2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    [462] 2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    [463] 5- {4- (aminosulfonyl) -3-fluorophenyl} -2,2-dimethyl-4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    [464] 2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -4- (4-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    [465] 2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -4- (4-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    [466] 2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -4- (4-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    [467] 5- {4- (aminosulfonyl) -3-fluorophenyl} -2,2-dimethyl-4- (4-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    [468] 2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -4- (4-nitrophenyl) -3 ( 2H ) -furanone;
    [469] 2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -4- (4-nitrophenyl) -3 ( 2H ) -furanone;
    [470] 2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -4- (4-nitrophenyl) -3 ( 2H ) -furanone;
    [471] 5- {4- (aminosulfonyl) -3-fluorophenyl} -2,2-dimethyl-4- (4-nitrophenyl) -3 ( 2H ) -furanone;
    [472] 4- (4-aminophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    [473] 4- (4-aminophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [474] 4- (4-aminophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [475] 4- (4-aminophenyl) -5- {4- (aminosulfonyl) -3-fluorophenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    [476] 4- {4- (acetylamino) phenyl} -2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    [477] 4- {4- (acetylamino) phenyl} -2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [478] 4- {4- (acetylamino) phenyl} -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [479] 4- {4- (acetylamino) phenyl} -5- {4- (aminosulfonyl) -3-fluorophenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    [480] 4- (3-chlorophenyl) -5- {3-fluoro-4- (methylthio) phenyl} -4- (3-methoxyphenyl) -3 ( 2H ) -furanone;
    [481] 4- (3-chlorophenyl) -5- {3-fluoro-4- (methylsulfonyl) phenyl} -4- (3-methoxyphenyl) -3 ( 2H ) -furanone;
    [482] 2,2-dimethyl-5- {2-fluoro-4- (methylthio) phenyl} -4-phenyl-3 ( 2H ) -furanone;
    [483] 2,2-dimethyl-5- {2-fluoro-4- (methylsulfinyl) phenyl} -4-phenyl-3 ( 2H ) -furanone;
    [484] 2,2-dimethyl-5- {2-fluoro-4- (methylsulfonyl) phenyl} -4-phenyl-3 ( 2H ) -furanone;
    [485] 5- {4- (aminosulfonyl) -2-fluorophenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    [486] 4- (2-chlorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    [487] 4- (2-chlorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [488] 4- (2-chlorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [489] 5- {4- (aminosulfonyl) -2-fluorophenyl} -4- (2-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [490] 4- (3-chlorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    [491] 4- (3-chlorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [492] 4- (3-chlorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [493] 5- {4- (aminosulfonyl) -2-fluorophenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [494] 2,2-dimethyl-5- {2-fluoro-4- (methylthio) phenyl} -4- (2-fluorophenyl) -3 ( 2H ) -furanone;
    [495] 2,2-dimethyl-5- {2-fluoro-4- (methylsulfinyl) phenyl} -4- (2-fluorophenyl) -3 ( 2H ) -furanone;
    [496] 2,2-dimethyl-5- {2-fluoro-4- (methylsulfonyl) phenyl} -4- (2-fluorophenyl) -3 ( 2H ) -furanone;
    [497] 5- {4- (aminosulfonyl) -2-fluorophenyl} -2,2-dimethyl-4- (2-fluorophenyl) -3 ( 2H ) -furanone;
    [498] 2,2-dimethyl-5- {2-fluoro-4- (methylthio) phenyl} -4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    [499] 2,2-dimethyl-5- {2-fluoro-4- (methylsulfinyl) phenyl} -4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    [500] 2,2-dimethyl-5- {2-fluoro-4- (methylsulfonyl) phenyl} -4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    [501] 5- {4- (aminosulfonyl) -2-fluorophenyl} -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    [502] 2,2-dimethyl-5- {2-fluoro-4- (methylthio) phenyl} -4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    [503] 2,2-dimethyl-5- {2-fluoro-4- (methylsulfinyl) phenyl} -4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    [504] 2,2-dimethyl-5- {2-fluoro-4- (methylsulfonyl) phenyl} -4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    [505] 5- {4- (aminosulfonyl) -2-fluorophenyl} -2,2-dimethyl-4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    [506] 4- (2,4-difluorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    [507] 4- (2,4-difluorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [508] 4- (2,4-difluorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [509] 5- {4- (aminosulfonyl) -2-fluorophenyl} -4- (2,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [510] 4- (2,5-difluorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    [511] 4- (2,5-difluorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [512] 4- (2,5-difluorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [513] 5- {4- (aminosulfonyl) -2-fluorophenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [514] 4- (3,4-difluorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    [515] 4- (3,4-difluorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [516] 4- (3,4-difluorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [517] 5- {4- (aminosulfonyl) -2-fluorophenyl} -4- (3,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [518] 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    [519] 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [520] 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [521] 5- {4- (aminosulfonyl) -2-fluorophenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [522] 2,2-dimethyl-5- {2-fluoro-4- (methylthio) phenyl} -4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    [523] 2,2-dimethyl-5- {2-fluoro-4- (methylsulfinyl) phenyl} -4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    [524] 2,2-dimethyl-5- {2-fluoro-4- (methylsulfonyl) phenyl} -4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    [525] 5- {4- (aminosulfonyl) -2-fluorophenyl} -2,2-dimethyl-4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    [526] 5- {3-bromo-4- (methylthio) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    [527] 5- {3-bromo-4- (methylsulfonyl) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    [528] 5- {3-bromo-4- (methylsulfinyl) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    [529] 5- {4- (aminosulfonyl) -3-bromophenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    [530] 5- {3-bromo-4- (methylthio) phenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [531] 5- {3-bromo-4- (methylsulfonyl) phenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [532] 5- {3-bromo-4- (methylsulfinyl) phenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [533] 5- {4- (aminosulfonyl) -3-bromophenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [534] 5- {3-bromo-4- (methylthio) phenyl} -4- (4-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [535] 5- {3-bromo-4- (methylsulfonyl) phenyl} -4- (4-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [536] 5- {3-bromo-4- (methylsulfinyl) phenyl} -4- (4-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [537] 5- {4- (aminosulfonyl) -3-bromophenyl} -4- (4-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [538] 5- {3-bromo-4- (methylthio) phenyl} -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    [539] 5- {3-bromo-4- (methylsulfonyl) phenyl} -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    [540] 5- {3-bromo-4- (methylsulfinyl) phenyl} -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    [541] 5- {4- (aminosulfonyl) -3-bromophenyl} -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    [542] 5- {3-bromo-4- (methylthio) phenyl} -2,2-dimethyl-4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    [543] 5- {3-bromo-4- (methylsulfonyl) phenyl} -2,2-dimethyl-4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    [544] 5- {3-bromo-4- (methylsulfinyl) phenyl} -2,2-dimethyl-4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    [545] 5- {4- (aminosulfonyl) -3-bromophenyl} -2,2-dimethyl-4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    [546] 5- {3-bromo-4- (methylthio) phenyl} -4- (2,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [547] 5- {3-bromo-4- (methylsulfonyl) phenyl} -4- (2,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [548] 5- {3-bromo-4- (methylsulfinyl) phenyl} -4- (2,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [549] 5- {4- (aminosulfonyl) -3-bromophenyl} -4- (2,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [550] 5- {3-bromo-4- (methylthio) phenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [551] 5- {3-bromo-4- (methylsulfonyl) phenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [552] 5- {3-bromo-4- (methylsulfinyl) phenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [553] 5- {4- (aminosulfonyl) -3-bromophenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [554] 5- {3-bromo-4- (methylthio) phenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [555] 5- {3-bromo-4- (methylsulfonyl) phenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [556] 5- {3-bromo-4- (methylsulfinyl) phenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [557] 5- {4- (aminosulfonyl) -3-bromophenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [558] 5- {3-bromo-4- (methylthio) phenyl} -2,2-dimethyl-4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    [559] 5- {3-bromo-4- (methylsulfonyl) phenyl} -2,2-dimethyl-4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    [560] 5- {3-bromo-4- (methylsulfinyl) phenyl} -2,2-dimethyl-4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    [561] 5- {4- (aminosulfonyl) -3-bromophenyl} -2,2-dimethyl-4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    [562] 5- {3-chloro-4- (methylthio) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    [563] 5- {3-chloro-4- (methylsulfonyl) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    [564] 5- {3-chloro-4- (methylsulfinyl) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    [565] 5- {4- (aminosulfonyl) -3-chlorophenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    [566] 5- {3-chloro-4- (methylthio) phenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [567] 5- {3-chloro-4- (methylsulfonyl) phenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [568] 5- {3-chloro-4- (methylsulfinyl) phenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [569] 5- {4- (aminosulfonyl) -3-chlorophenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [570] 5- {3-chloro-4- (methylthio) phenyl} -4- (4-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [571] 5- {3-chloro-4- (methylsulfonyl) phenyl} -4- (4-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [572] 5- {3-chloro-4- (methylsulfinyl) phenyl} -4- (4-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [573] 5- {4- (aminosulfonyl) -3-chlorophenyl} -4- (4-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [574] 5- {3-chloro-4- (methylthio) phenyl} -4- (3-fluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [575] 5- {3-chloro-4- (methylsulfonyl) phenyl} -4- (3-fluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [576] 5- {3-chloro-4- (methylsulfinyl) phenyl} -4- (3-fluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [577] 5- {4- (aminosulfonyl) -3-chlorophenyl} -4- (3-fluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [578] 5- {3-chloro-4- (methylthio) phenyl} -4- (4-fluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [579] 5- {3-chloro-4- (methylsulfonyl) phenyl} -4- (4-fluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [580] 5- {3-chloro-4- (methylsulfinyl) phenyl} -4- (4-fluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [581] 5- {4- (aminosulfonyl) -3-chlorophenyl} -4- (4-fluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [582] 5- {3-chloro-4- (methylthio) phenyl} -4- (2,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [583] 5- {3-chloro-4- (methylsulfonyl) phenyl} -4- (2,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [584] 5- {3-chloro-4- (methylsulfinyl) phenyl} -4- (2,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [585] 5- {4- (aminosulfonyl) -3-chlorophenyl} -4- (2,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [586] 5- {3-chloro-4- (methylthio) phenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [587] 5- {3-chloro-4- (methylsulfonyl) phenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [588] 5- {3-chloro-4- (methylsulfinyl) phenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [589] 5- {4- (aminosulfonyl) -3-chlorophenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [590] 5- {3-chloro-4- (methylthio) phenyl} -4- (3,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [591] 5- {3-chloro-4- (methylsulfonyl) phenyl} -4- (3,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [592] 5- {3-chloro-4- (methylsulfinyl) phenyl} -4- (3,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [593] 5- {4- (aminosulfonyl) -3-chlorophenyl} -4- (3,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [594] 5- {3-chloro-4- (methylthio) phenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [595] 5- {3-chloro-4- (methylsulfonyl) phenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [596] 5- {3-chloro-4- (methylsulfinyl) phenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [597] 5- {4- (aminosulfonyl) -3-chlorophenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [598] 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-methyl-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    [599] 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-methyl-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [600] 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-methyl-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [601] 5- {4- (aminosulfonyl) -3-methylphenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [602] 5- {3-chloro-4- (methylthio) phenyl} -2,2-dimethyl-4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    [603] 5- {3-chloro-4- (methylsulfonyl) phenyl} -2,2-dimethyl-4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    [604] 5- {3-chloro-4- (methylsulfinyl) phenyl} -2,2-dimethyl-4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    [605] 5- {4- (aminosulfonyl) -3-chlorophenyl} -2,2-dimethyl-4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    [606] 5- {2-chloro-4- (methylthio) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    [607] 5- {2-chloro-4- (methylsulfinyl) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    [608] 5- {2-chloro-4- (methylsulfonyl) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    [609] 5- {4- (aminosulfonyl) -2-chlorophenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    [610] 5- {2-chloro-4- (methylthio) phenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [611] 5- {2-chloro-4- (methylsulfonyl) phenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [612] 5- {2-chloro-4- (methylsulfinyl) phenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [613] 5- {4- (aminosulfonyl) -2-chlorophenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [614] 5- {2-chloro-4- (methylthio) phenyl} -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    [615] 5- {2-chloro-4- (methylsulfinyl) phenyl} -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    [616] 5- {2-chloro-4- (methylsulfonyl) phenyl} -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    [617] 5- {4- (aminosulfonyl) -2-chlorophenyl} -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    [618] 5- {2-chloro-4- (methylthio) phenyl} -2,2-dimethyl-4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    [619] 5- {2-chloro-4- (methylsulfinyl) phenyl} -2,2-dimethyl-4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    [620] 5- {2-chloro-4- (methylsulfonyl) phenyl} -2,2-dimethyl-4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    [621] 5- {4- (aminosulfonyl) -2-chlorophenyl} -2,2-dimethyl-4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    [622] 5- {2-chloro-4- (methylthio) phenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [623] 5- {2-chloro-4- (methylsulfonyl) phenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [624] 5- {2-chloro-4- (methylsulfinyl) phenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [625] 5- {4- (aminosulfonyl) -2-chlorophenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [626] 5- {2-chloro-4- (methylthio) phenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [627] 5- {2-chloro-4- (methylsulfonyl) phenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [628] 5- {2-chloro-4- (methylsulfinyl) phenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [629] 5- {4- (aminosulfonyl) -2-chlorophenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [630] 2,2-dimethyl-5- {3-methyl-4- (methylthio) phenyl} -4-phenyl-3 ( 2H ) -furanone;
    [631] 2,2-dimethyl-5- {3-methyl-4- (methylsulfinyl) phenyl} -4-phenyl-3 ( 2H ) -furanone;
    [632] 2,2-dimethyl-5- {3-methyl-4- (methylsulfonyl) phenyl} -4-phenyl-3 ( 2H ) -furanone;
    [633] 5- {4- (aminosulfonyl) -3-methylphenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    [634] 2,2-dimethyl-4- (3-fluorophenyl) -5- {3-methyl-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    [635] 2,2-dimethyl-4- (3-fluorophenyl) -5- {3-methyl-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [636] 2,2-dimethyl-4- (3-fluorophenyl) -5- {3-methyl-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [637] 5- {4- (aminosulfonyl) -3-methylphenyl} -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    [638] 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-methyl-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    [639] 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-methyl-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    [640] 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-methyl-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [641] 5- {4- (aminosulfonyl) -3-methylphenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [642] 5- {3-chloro-4- (N-methylaminosulfonyl) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    [643] 5- {3-chloro-4- (N-ethylaminosulfonyl) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    [644] 5- [4-{(acetylamino) sulfonyl} -3-chlorophenyl] -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    [645] 5- [3-chloro-4-{(Nn-propionylamino) sulfonyl} phenyl] -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    [646] 5- [3-chloro-4-{(Nn-butyrylamino) sulfonyl} phenyl] -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    [647] 4- (3-chlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl}-( 2H ) -furan-3-thione;
    [648] 4- (3-chlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl}-( 2H ) -furan-3-thione;
    [649] 4- (3-chlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl}-( 2H ) -furan-3-thione;
    [650] 5- {4- (aminosulfonyl) -3-fluorophenyl} -4- (3-chlorophenyl) -2,2-dimethyl- ( 2H ) -furan-3-thione;
    [651] 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-fluoro- (4-methylthio) phenyl}-( 2H ) -furan-3-thione;
    [652] 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-fluoro- (4-methylsulfonyl) phenyl}-( 2H ) -furan-3-thione;
    [653] 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-fluoro- (4-methylsulfinyl) phenyl}-( 2H ) -furan-3-thione;
    [654] 5-{(4-aminosulfonyl) -3-fluorophenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl- ( 2H ) -furan-3-thione;
    [655] In formula (I), the formula Particularly preferred sub-series compounds of (V) or pharmaceutically acceptable salts thereof;
    [656]
    [657] (Ⅴ)
    [658] Food,
    [659] Y is alkylsulfonyl, aminosulfonyl, alkylsulfinyl, (N-acylamino) sulfonyl, (N-alkylamino) sulfonyl, or alkylthio;
    [660] Z is oxygen or sulfur atom;
    [661] R 1 and R 2 are independently selected from methyl and ethyl groups; And,
    [662] AR is an aromatic group consisting of 5 to 10 substituted or unsubstituted atoms, with the exception of substituted or unsubstituted phenyl groups.
    [663] Preferred classes of compounds include compounds of formula (V) or pharmaceutically acceptable salts thereof;
    [664] Food,
    [665] Y is selected from (lower alkyl) sulfonyl, aminosulfonyl and (lower N-acylamino) sulfonyl;
    [666] Z is selected from oxygen and sulfur atoms;
    [667] R 1 and R 2 are independently selected from methyl and ethyl groups; And,
    [668] AR is selected from the following specific aromatic groups:
    [669]
    [670] Wherein R 8 to R 19 , when present, are each selected from hydrido, halo, lower alkyl, lower acyl, lower haloalkyl, lower alkoxy, formyl, cyano, nitro, amino, azido and N-acylamino do.
    [671] Particularly preferred classes of compounds include compounds of formula (V) or pharmaceutically acceptable salts thereof;
    [672] Food,
    [673] Y is selected from methylsulfonyl, ethylsulfonyl, aminosulfonyl, (N-acetylamino) sulfonyl and (N-propionylamino) sulfonyl;
    [674] Z is selected from oxygen and sulfur atoms;
    [675] R 1 and R 2 are independently selected from methyl and ethyl groups; And,
    [676] R 8 to R 19 in the presence of hydrido, fluoro, chloro, bromo, methyl, ethyl, isopropyl, acetyl, n-propionyl, trifluoromethyl, methoxy, ethoxy and formyl, respectively Is selected.
    [677] Particularly preferred groups of specific compounds in formula (V) include the following compounds and pharmaceutically acceptable salts thereof:
    [678] 2,2-dimethyl-5- {4- (methylthio) phenyl} -4- (3-thienyl) -3 ( 2H ) -furanone;
    [679] 2,2-dimethyl-4- {2- (3-methylthienyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [680] 2,2-dimethyl-4- {2- (5-formylthienyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [681] 4- (2-benzo [b] thienyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [682] 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (1-naphthyl) -3 ( 2H ) -furanone;
    [683] 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (3-pyridyl) -3 ( 2H ) -furanone;
    [684] 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (2-pyridyl) -3 ( 2H ) -furanone;
    [685] 4- (2-benzo [b] furanyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [686] 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (2-naphthyl) -3 ( 2H ) -furanone;
    [687] 2,2-dimethyl-4- {5- (2-fluorothienyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [688] 2,2-dimethyl-4- {5- (3-fluorothienyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [689] 2,2-dimethyl-4- {4- (2-fluorothienyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [690] 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (2-thienyl) -3 ( 2H ) -furanone;
    [691] 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (3-thienyl) -3 ( 2H ) -furanone;
    [692] 4- {2- (5-acetylthienyl)}-2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [693] 2,2-dimethyl-4- (2-furanyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [694] 2,2-dimethyl-4- (3-furanyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [695] 2,2-dimethyl-4- {5- (3-fluorofuranyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [696] 2,2-dimethyl-4- {5- (2-fluorofuranyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [697] 2,2-dimethyl-4- {4- (2-fluorofuranyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [698] 2,2-dimethyl-4- {4- (1-N-methylpyrazolyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [699] 2,2-dimethyl-4- {4- (1-N-ethylpyrazolyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [700] 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (4-pyridyl) -3 ( 2H ) -furanone;
    [701] 2,2-dimethyl-4- {3- (6-methoxypyridyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [702] 2,2-dimethyl-4- {4- (1-N-isopropylpyrazolyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [703] 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (5-pyrimidinyl) -3 ( 2H ) -furanone;
    [704] 2,2-dimethyl-4- {3- (6-methylpyridyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [705] 2,2-dimethyl-4- {2- (5-formyl-4-methylthienyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [706] 2,2-dimethyl-4- [2- {5- (1,3-dioxolane) -2-yl} thienyl] -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -fu Lanone;
    [707] 4- {2- (5-bromothienyl)}-2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [708] 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (4-pyrazolyl) -3 ( 2H ) -furanone;
    [709] 5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-4- (2-pyridyl) -3 ( 2H ) -furanone;
    [710] 5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-4- (3-pyridyl) -3 ( 2H ) -furanone;
    [711] 5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-4- (4-pyridyl) -3 ( 2H ) -furanone;
    [712] 5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-4- {4- (1-N-methylpyrazolyl)}-3 ( 2H ) -furanone;
    [713] 5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- {4- (1-N-ethylpyrazolyl)}-2-methyl-3 ( 2H ) -furanone;
    [714] 5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-4- {4- (1-N-isopropylpyrazolyl)}-3 ( 2H ) -furanone;
    [715] 5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-4- (3-thienyl) -3 ( 2H ) -furanone;
    [716] 5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- {4- (2-fluorothienyl)}-2-methyl-3 ( 2H ) -furanone;
    [717] 5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- {5- (2-fluorothienyl)}-2-methyl-3 ( 2H ) -furanone;
    [718] 5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- {5- (3-fluorothienyl)}-2-methyl-3 ( 2H ) -furanone;
    [719] 5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- (2-furanyl) -2-methyl-3 ( 2H ) -furanone;
    [720] 5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- (3-furanyl) -2-methyl-3 ( 2H ) -furanone;
    [721] 5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- {5- (3-fluorofuranyl)}-2-methyl-3 ( 2H ) -furanone;
    [722] 5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- {4- (2-fluorofuranyl)}-2-methyl-3 ( 2H ) -furanone;
    [723] 5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- {5- (2-fluorofuranyl)}-2-methyl-3 ( 2H ) -furanone;
    [724] 2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -4- (3-thienyl) -3 ( 2H ) -furanone;
    [725] 2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -4- (2-thienyl) -3 ( 2H ) -furanone;
    [726] 2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -4- (2-pyridyl) -3 ( 2H ) -furanone;
    [727] 2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -4- (4-pyridyl) -3 ( 2H ) -furanone;
    [728] 2,2-diethyl-4- {4- (1-N-methylpyrazolyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [729] 2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- (3-pyridyl) -3 ( 2H ) -furanone;
    [730] 2-ethyl-2-methyl-4- {4- (1-N-methylpyrazolyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [731] 2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- (4-pyrazolyl) -3 ( 2H ) -furanone;
    [732] 2-ethyl-4- {4- (1-N-ethylpyrazolyl)}-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [733] 2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- {4- (1-N-isopropylpyrazolyl)}-3 ( 2H ) -furanone;
    [734] 2-ethyl-2-methyl-4- {3- (6-methoxypyridyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [735] 2-ethyl-2-methyl-4- {3- (6-methylpyridyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [736] 2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- (3-thienyl) -3 ( 2H ) -furanone;
    [737] 2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- {4- (2-fluorothienyl)}-3 ( 2H ) -furanone;
    [738] 2-ethyl-4- (2-furanyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [739] 2-ethyl-4- (3-furanyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [740] 2-ethyl-4- {5- (3-fluorofuranyl)}-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [741] 2-ethyl-4- {5- (2-fluorofuranyl)}-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [742] 2-ethyl-4- {4- (2-fluorofuranyl)}-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [743] 4- (2-benzo [b] thienyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [744] 4- (2-benzo [b] furanyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [745] 2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- (2-thienyl) -3 ( 2H ) -furanone;
    [746] 2-ethyl-4- {5- (2-fluorothienyl)}-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [747] 4- {2- (5-acetylthienyl)}-2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    [748] 2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- {2- (5-methylthienyl)}-3 ( 2H ) -furanone;
    [749] 2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- {2- (3-methylthienyl)}-3 ( 2H ) -furanone;
    [750] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (2-furanyl) -3 ( 2H ) -furanone;
    [751] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (3-furanyl) -3 ( 2H ) -furanone;
    [752] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {5- (3-fluorofuranyl)}-3 ( 2H ) -furanone;
    [753] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {5- (2-fluorofuranyl)}-3 ( 2H ) -furanone;
    [754] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {4- (2-fluorofuranyl)}-3 ( 2H ) -furanone;
    [755] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (3-thienyl) -3 ( 2H ) -furanone;
    [756] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (2-thienyl) -3 ( 2H ) -furanone;
    [757] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {4- (2-fluorothienyl)}-3 ( 2H ) -furanone;
    [758] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {5- (2-fluorothienyl)}-3 ( 2H ) -furanone;
    [759] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {5- (3-fluorothienyl)}-3 ( 2H ) -furanone;
    [760] 5- {4- (aminosulfonyl) phenyl} -4- (2-benzo [b] thienyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [761] 5- {4- (aminosulfonyl) phenyl} -4- (2-benzo [b] furanyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    [762] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (2-naphthyl) -3 ( 2H ) -furanone;
    [763] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (1-naphthyl) -3 ( 2H ) -furanone;
    [764] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (2-pyridyl) -3 ( 2H ) -furanone;
    [765] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (3-pyridyl) -3 ( 2H ) -furanone;
    [766] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (4-pyridyl) -3 ( 2H ) -furanone;
    [767] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {4- (1-N-methylpyrazolyl)}-3 ( 2H ) -furanone;
    [768] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {4- (1-N-ethylpyrazolyl)}-3 ( 2H ) -furanone;
    [769] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {4- (1-N-isopropylpyrazolyl)}-3 ( 2H ) -furanone;
    [770] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (4-pyrazolyl) -3 ( 2H ) -furanone;
    [771] The terms and abbreviations used above are described in the following table.
    [772] Terms / abbreviations Explanation Alkyl Linear or branched alkyl groups of 1 to 10 carbon atoms. Haloalkyl Alkyl groups substituted with one or more halogen atoms, such as fluoromethyl (F-CH 2- ), 1-chloroethyl (CH 3 -CHCI-), trifluoromethyl (CF 3- ), and the like. Hydroxyalkyl The alkyl group substituted with one or more hydroxyl groups Examples are hydroxymethyl (HO-CH 2 -) - and the like, 2-hydroxyethyl (HO-CH 2 CH 2) . Hydrido Single hydrogen atom Halo Halogen atoms such as fluorine, chlorine, bromine or iodine Alkyloxy Alkyloxy group having an alkyl group having 1 to 10 carbon atoms, for example, methoxy, ethoxy, propoxy, isopropoxy, t-butoxy and the like. Alkyloxy is the same as "alkoxy". Low When used with alkyl, haloalkyl, hydroxyalkyl, N-alkylamino, N-acylamino and the like, alkyl groups having 1 to 5 carbon atoms are shown. For example, "lower haloalkyl" refers to an alkyl group having 1 to 5 carbon atoms substituted with one or more halogen atoms. Alkylthio Alkyl group substituted with sulfur atom. Examples include methylthio (CH 3 -S-), ethylthio (CH 3 CH 2 -S-). Alkylsulfonyl "-SO 2- " substituted with an alkyl group. Examples include methylsulfonyl (CH 3 -SO 2- ), ethylsulfonyl (CH 3 CH 2 -SO 2- ), and the like. Aminosulfonyl "-SO 2- " substituted with an amino (-NH 2 ) group (NH 2 -SO 2- ). (N-alkylamino) sulfonyl "-SO 2- " substituted with an N-alkylamino group. Examples include (N-methylamino) sulfonyl (CH 3 -NH-SO 2- ), (N-ethylamino) sulfonyl (CH 3 CH 2 -NH-SO 2- ), and the like. (N-acylamino) sulfonyl An aminosulfonyl group substituted with an acyl group at a nitrogen atom. Examples are (N-acetylamino) sulfonyl [CH 3 C (O) -NH-SO 2- ], (N-propionylamino) sulfonyl [CH 3 CH 2 C (O) -NH-SO 2- ] Etc. Haloalkoxy Alkoxy groups substituted with one or more halogen atom (s). Examples include fluoromethoxy (FCH 2 O—), 2-chloroethoxy (ClCH 2 —CH 2 —O—), trifluoromethoxy (CF 3 O—), and the like. Alkoxyalkyl Alkyl group substituted with an alkoxy group. Examples are methoxymethyl (CH 3 -O-CH 2- ), 1-methoxy-n-propyl- [CH 3 -CH 2 -CH (OCH 3 )-] and the like. Formyl "CHO-" flag Acyl "-C (O)-" substituted with an alkyl group. Examples are acetyl [CH 3 -C (O)-], propionyl [CH 3 CH 2 -C (O)-], and the like. N-acylamino "-NH-" substituted with an acyl group. Examples include N-acetylamino [CH 3 C (O) —NH—], N-propionylamino [CH 3 CH 2 C (O) —NH—] and the like. Alkylsulfinyl "-S (O)-" substituted with an alkyl group. Examples include methylsulfinyl [CH 3 -S (O)-], ethylsulfinyl [CH 3 CH 2 S (O)-] and the like. Methylenedioxy "-O-CH 2 -O-" group N, N-dialkylamino An amino group substituted with two alkyl groups. Examples include N, N-dimethylamino [(CH 3 ) 2 N-], N, N-methyl-ethylamino [CH 3 -N-CH 2 CH 3- ], and the like.
    [773] General Synthetic Process
    [774] Most compounds of the present invention can be synthesized by the synthesis process of Schemes 1-8, wherein the substituents R 1 to R 19 , X, Y, Z and AR are defined in formula (I), unless otherwise noted As it is. Various compounds of the present invention can be prepared with minor changes, such as changing the reagents, solvents, and reaction sequences used in the synthesis of Schemes 1-8. Some compounds of the present invention were synthesized according to procedures not included in the scope of Schemes 1-8, and detailed synthesis procedures for these compounds are described in their respective preparations.
    [775]
    [776] Scheme (1) is based on 1,1-dialkyl-2-propyn-1-ol (a) which can be obtained commercially or easily as a starting material, and 2,2-dialkyl-4-aryl-5- A six-step process for preparing {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone (g) is shown. In the first step, lithium acetylenide of (a) prepared by adding n-butyllithium in situ to THF solution of starting material (a) at -78 ° C., Reaction with 4- (methylthio) benzaldehyde yields diol (b). In the second step, the benzyl hydroxyl group of (b) is oxidized to the corresponding carbonyl group of (c) using an oxidizing agent such as pyridinium dichromate, manganese dioxide, chromium trioxide and the like. In the third step, diethylamine is used as a catalyst in an alcohol solvent to cyclize the acyclic ketone (c) to obtain 3 ( 2H ) -furanone (d) [J. Chem. Soc. 3871 (1958)]. In the fourth step, sulfide (d) is reacted with oxone and oxidized to the corresponding sulfone (e). In the fifth step, (e) is reacted with iodine in the presence of bromine in acetic acid or a catalytic amount of BTI [{bis (trifluoroacetoxy) iodo} benzene] to yield 5-aryl-2,2-dialkyl-3 ( 2H )- Furanone (e) is halogenated to give (f). In the sixth step, a halide f is subjected to an aromatic bonding reaction via palladium (0) using an appropriate arylboronic acid to obtain a diaryl compound (g) [Suzuki Coupling: J. Org. Chem. 59 , 5524 (1994). As long as the desired compound can be prepared through the prerequisite procedure, the order of reactions in each reaction scheme can be changed. For example, instead of performing the fourth stage of the oxidation reaction of Scheme (1) followed by the fifth stage of the halogenation reaction, the fifth stage of the halogenation reaction is performed first, followed by the fourth stage of the oxidation reaction. can do.
    [777]
    [778] Scheme (2) is for preparing 4-aryl-5- {4- (aminosulfonyl) phenyl} -3 ( 2H ) -furanone (k) from the sulfide intermediate (d) synthesized in scheme (1). A four-step manufacturing process is shown. In the first step, sulfide (d) is partially oxidized using m-chloroperbenzoic acid (m-CPBA) to form sulfoxide (h). In the second step, the halide (i) is obtained by halogenating the sulfoxide (h) using iodine in the presence of bromine in acetic acid or a catalytic amount of BTI as in Scheme I. In the third step, halides (i) are converted according to literature into 1) trifluoroacetic anhydride (TFAA), 2) triethylamine (TEA) in methanol, 3) chlorine in acetic acid, and then 4) ammonia water. Treatment to synthesize the sulfonamide group (j): [J. Am. Chem. Soc. 73 , 3240 (1951). In the fourth step, sulfonamide (j) is combined with a suitable aromatic boronic acid in the presence of a palladium (0) catalyst to give 4,5-diaryl-3 ( 2H ) -furanone (k).
    [779]
    [780] Scheme (3) represents a three step preparation process for the synthesis of 4,5-diaryl-3 ( 2H ) -furanone (o) wherein the 5- {4- (methylsulfonyl) phenyl} group is "X" Replace with. In the first step, substituted thioanisole (l) is reacted with aromatic acetylchloride in the presence of aluminum chloride (AlCl 3 ) to give ketone (m) (Friedel-Craft acylation). In the second step, ketone (m) is reacted with " C-acylation " with α-bromoisobutyryl cyanide using sodium hydride as the base. Further acylation reactions yield (n), the product of intramolecular cyclization. In the third step, oxone is used to oxidize sulfide (n) to give methyl sulfone (o). By replacing thioaniazole (I) with (alkylthio) benzene derivatives, the scope of Scheme (3) can be extended to the range for synthesizing alkylsulfone compounds similar to compound (o). It is also possible to change the reaction sequence of Scheme (3), where the methylthio group is oxidized (3 steps) prior to the reaction with α-bromoisobutyryl cyanide (2 steps) to obtain the same target product (o). Can be. Accordingly, the compounds of the present invention may be prepared by various modifications of Scheme (3).
    [781]
    [782] Scheme (4) shows a two step synthesis process for synthesizing sulfonamide (q). In the first step, methylsulfide (n) is reacted with m-CPBA to give sulfoxide (p). In the second step, sulfoxide (p) is converted into sulfonamide (q) by reacting in order with 1) trifluoroacetic anhydride, 2) triethylamine in methanol, 3) chlorine in acetic acid and then 4) ammonia water. .
    [783]
    [784] Scheme (5) shows a one step synthesis process for preparing thiocarbonyl compound (s). In Scheme (5), 4,5-diaryl-3 ( 2H ) -furanone (r) is reacted with Lawson's Reagent to obtain the corresponding thiocarbonyl compound (s).
    [785]
    [786] Scheme (6) shows a two step synthesis process for the synthesis of N-alkylsulfonamides (u) from sulfoxide (p). In the first step, sulfoxide (p) is reacted in order with 1) trifluoro acetic anhydride, 2) triethylamine in methanol, and then 3) chlorine in acetic acid in order to convert to the corresponding sulfonylchloride. In the second step, sulfonylchloride (t) is reacted with alkylamine or ammonia to give N-alkylsulfonamide (u).
    [787]
    [788] Scheme (7) shows a one step synthesis process for synthesizing N-acylsulfonamide (v). Sulfonamide (q) is reacted with alkanoic anhydride under tetrahydrofuran to give (v).
    [789] As shown in the following Scheme (8), the reaction sequence of Scheme (I) was modified so that 5- {4- (methylthio) phenyl} -3 ( 2H ) -furanone (x) and 5- {4- ( Methylsulfinyl) phenyl} -3 ( 2H ) -furanone (y) can be prepared.
    [790]
    [792] The following examples include a detailed description of the preparation of compounds of formulas 1-5. The detailed description of these examples is for illustrative purposes only and is not intended to limit the invention to them. Most of these detailed descriptions fall within the scope of the general synthetic procedures disclosed above and are used to illustrate general synthetic procedures, wherein the general synthetic procedures form part of the present invention. All chromatographic separations in the examples presented were carried out using silica gel, unless otherwise noted. Abbreviations used in the following examples are defined in the following table.
    [793] AbbreviationJustice ℃Degrees Celsius mpMelting point. Uncalibrated value NMRProton nuclear magnetic resonance. All NMR spectra are at 300 MHz NMR. The NMR solvent in the present invention is CDCl 3 , unless otherwise noted. In the NMR data of the present invention, the following widely-accepted abbreviations were used: single peak s, double peak d, triple peak t, quad peak q, wide single peak brs, and the like. IRInfrared spectrum. All IR spectra are taken in neat form on the KBr window, unless otherwise noted, and the unit is cm −1 . MSMass spectrum. All MS data are expressed in units of m / e . FABHigh speed atomic shock EIElectron ionization THFTetrahydrofuran mIon peak for molecular weight in MS data, thus (m + 1) corresponds to the parent molecule peak with one proton
    [794] Example 1
    [795] 2,2-dimethyl-4- (4-methylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [796]
    [797] Step 1: Preparation of 1- {4- (methylthio) phenyl} -4-hydroxy-4-methyl-2-pentin-1-ol
    [798]
    [799] 2-Methyl-3-butyn-2-ol (416 mg) was dissolved in anhydrous THF (30 mL) at -78 ° C and argon, and stirred in 1.6 M butyllithium (5 mL) dissolved in hexane. Dropwise over 10 minutes. After 20 minutes, p -methylthiobenzaldehyde (0.5 mL) was added dropwise to the reaction solution. The cold bath was removed, and the temperature of the reaction solution was raised to room temperature. After the reaction mixture was stirred for 2 hours, the reaction solvent was removed under reduced pressure and neutralized with dilute HCl aqueous solution. The reaction mixture was extracted with dichloromethane (50 mL × 3), and then the dichloromethane layer was washed with water (50 mL × 1). The dichloromethane layer was concentrated under reduced pressure, and the remaining residue was separated by column chromatography (hexane / ethyl acetate = 1: 1) to give 1- {4- (methylthio) phenyl} -4-hydroxy-4-methyl-. 724 mg of 2-pentin-1-ol were obtained. NMR: δ 1.54 (s, 6H), 2.36 (s, 1H), 2.48 (s, 3H), 2.62 (d, 1H), 5.43 (d, J = 5.4 Hz, 1H), 7.25 (d, J = 6.9 Hz, 2H), 7.43 (d, J = 6.9 Hz, 2H).
    [800] Step 2: Preparation of 1-{(4-methylthio) phenyl} -4-hydroxy-4-methyl-2-pentin-1-one
    [801]
    [802] 724 mg of 1- {4- (methylthio) phenyl} -4-hydroxy-4-methyl-2-pentin-1-ol was dissolved in 30 ml of acetone, and then dissolved in 10 ml of water and 0.25 ml of concentrated sulfuric acid. 451 mg of chromium trioxide was slowly added dropwise. The reaction solution was stirred overnight at room temperature and then concentrated under reduced pressure. The remaining aqueous residue was extracted with 50 mL of water and dichloromethane (50 mL × 3). The organic layer was concentrated under reduced pressure, and the remaining residue was separated by column chromatography (hexane / ethyl acetate = 1: 1) to obtain solid 1-{(4-methylthio) phenyl} -4-hydroxy-4-methyl. 200 mg of -2-pentin-l-one were obtained. mp: 102-103 o C. NMR: δ 1.67 (s, 6H), 2.41 (s, 1H), 2.54 (s, 3H), 7.28 (d, J = 8.7 Hz, 2H), 8.02 (d, J = 8.7 Hz, 2H). IR (cm −1 ): 3404, 1613, 1176, 747.
    [803] In addition, 1-{(4-methylthio) phenyl} -4-hydroxy-4-methyl-2-pentyn-1-one was synthesized using pyridinium dichromate (PDC) instead of chromium trioxide as follows: 1- {4- (methylthio) phenyl} -4-hydroxy-4-methyl-2-pentin-1-ol (20 g) and celite (celite, 30 g) are suspended in 500 ml of dichloromethane and stirred Thereafter, PDC (40 g) was added in small portions over 10 minutes. The reaction mixture was stirred at rt for 12 h. The suspension was filtered through a Florisil pad (150 g) and the Florisil pad was washed with 500 ml of methylene chloride. The filtrate was washed with dilute hydrochloric acid aqueous solution (200 mL × 1), and the organic layer was concentrated under reduced pressure. The remaining residue was chromatographed as above to give 12.3 g of 1-{(4-methylthio) phenyl} -4-hydroxy-4-methyl-2-pentin-1-one.
    [804] 1-{(4-methylthio) phenyl} -4-hydroxy-4-methyl- from 1- {4- (methylthio) phenyl} -4-hydroxy-4-methyl-2-pentin-1-ol Another oxidation reaction for preparing 2-pentyn-1-one is as follows: 1- {4- (methylthio) phenyl} -4-hydroxy-4-methyl-2- in methylene chloride (2 L). A suspension of fentin-1-ol (150 g) and activated manganese dioxide (200 g) was stirred at room temperature for 20 hours using an overhead stirrer. The suspension was then filtered through celite (300 g) and the filtrate was concentrated under reduced pressure. The remaining solid crude was recrystallized from ethyl acetate / hexane to give 120 g of 1-{(4-methylthio) phenyl} -4-hydroxy-4-methyl-2-pentin-1-one.
    [805] Step 3: 2,2-dimethyl-5- {4- (methylthio) phenyl} -3 ( 2H) -Production of Furanone
    [806]
    [807] 1-{(4-methylthio) phenyl} -4-hydroxy-4-methyl-2-pentin-l-one (120 mg) was dissolved in 20 ml of ethanol, stirred, and diluted with 7 ml of ethanol. 0.08 ml of ethylamine was added dropwise at room temperature over 5 minutes. The reaction solution was further stirred for 1 hour, and then the solvent was removed under reduced pressure. The remaining residue was diluted with 50 mL of water and extracted with dichloromethane (30 mL × 3). The organic layer was concentrated under reduced pressure, and then the remaining residue was purified by column chromatography (hexane / ethyl acetate = 4: 1) to give a solid 2,2-dimethyl-5- {4- (methylthio) phenyl} -3 ( 2H ). 90 mg of furanone was obtained. mp: 107-109 ° C. NMR: δ 1.48 (s, 6H), 2.54 (s, 3H), 5.91 (s, 1H), 7.30 (d, J = 8.4 Hz, 2H), 7.72 (d, J = 8.4 Hz, 2H). IR (cm -1 ): 1676, 1579, 1485, 1376, 1174, 1095, 1050, 809
    [808] Step 4: 4-bromo-2,2-dimethyl-5- {4- (methylthio) phenyl} -3 ( 2H) -Production of Furanone
    [809]
    [810] 2,2-dimethyl-5- {4- (methylthio) phenyl} -3 ( 2H ) furanone (45 mg) was dissolved in 20 ml of carbon tetrachloride and stirred in acetic acid (0.5 ml) and bromine (0.1 ml). ) Was added. After the reaction solution was stirred at room temperature for 1 hour, 20 ml of saturated aqueous sodium thiosulfate solution was added to stop the reaction. After the carbon tetrachloride was removed under reduced pressure, the remaining aqueous layer was extracted with dichloromethane (50 mL × 3), and the organic layer was washed with water (50 mL × 1). The organic layer was concentrated under reduced pressure, and the remaining residue was then subjected to column chromatography (hexane / ethyl acetate = 2: 1) to give 4-bromo-2,2-dimethyl-5- {4- (methylthio) phenyl as a solid. } 69 mg of 3 ( 2H ) -furanone were obtained. NMR: δ 1.52 (s, 6H), 2.55 (s, 3H), 7.33 (d, J = 9.3 Hz, 2H), 8.15 (d, J = 9.0 Hz, 2H); IR (cm -1 ): 1704, 1594, 1574, 1486, 1348, 1184, 1069.
    [811] Step 5: 4-bromo-2,2-dimethyl-5- {4- (4-methylsulfonyl) phenyl} -3 ( 2H) -Production of Furanone
    [812]
    [813] After dissolving 42 mg of 4-bromo-2,2-dimethyl-5- {4- (methylthio) phenyl} -3 ( 2H ) -furanone in 15 ml of THF and 15 ml of ethanol, 178 mg of oxone was added dropwise. It was. The mixture was stirred overnight at room temperature and then removed under reduced pressure to remove the solvent. The remaining residue was extracted with 50 mL of water and methylene chloride (50 mL × 3). The organic layer was concentrated under reduced pressure to remove the solvent, and the residue was separated by column chromatography (hexane / ethyl acetate = 2: 1) to give the desired solid 4-bromo-2,2-dimethyl-5- {4. 45 mg of-(methylsulfonyl) phenyl} -3 ( 2H ) -furanone were obtained. mp: 196-196.5 ° C. NMR: δ 1.57 (s, 6H), 3.11 (s, 3H), 8.11 (d, J = 8.7 Hz, 2H), 8.40 (d, J = 8.7 Hz, 2H). IR (cm <-1> ): 2928, 1703, 1559, 1270, 1148, 1076, 847. MS (EI): 346 ( m ).
    [814] Step 6: 2,2-dimethyl-4- (4-methylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H) -Production of Furanone
    [815] 4-bromo-2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone (110 mg) and tetrakis (triphenyl) palladium (0) (54 mg) 2 M aqueous sodium carbonate solution (0.22 ml) and 4-methyl-benzeneboronic acid (60 mg) were added dropwise to a solution obtained by dissolving in 30 ml of benzene. The reaction solution was stirred with reflux for 24 hours. The solvent was then evaporated under reduced pressure and the remaining residue was extracted with 50 mL of water and dichloromethane (50 mL × 3). The organic layer was concentrated under reduced pressure, and the remaining residue was separated by column chromatography (hexane / ethyl acetate = 2: 1) to give a solid 2,2-dimethyl-4- (4-methylphenyl) -5- {4- (methyl 76 mg of sulfonyl) phenyl} -3 ( 2H ) -furanone was obtained. mp: 167-168 ° C. NMR: δ 1.57 (s, 6H), 2.38 (s, 3H), 3.07 (s, 3H), 7.17 (m, 4H), 7.89 (m, 4H). IR (cm <-1> ): 1707, 1660, 1531, 1289, 1230. MS (EI): 356 ( m ).
    [816] Example 2
    [817] 4- (3-chloro-4-fluorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [818]
    [819] 4-Bromo-2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone (112 mg) and tetrakis (triphenylphosphine) palladium (0) (54 Mg) was dissolved in 7 ml of benzene and 1 ml of ethanol, and 2M aqueous sodium carbonate solution (0.22 ml) and (3-chloro-4-fluorophenyl) boronic acid (82 mg) were added thereto. The reaction solution was refluxed for 24 hours. The solvent was evaporated under reduced pressure and the remaining residue was extracted with 50 mL of water and dichloromethane (50 mL x 3). The organic layer was concentrated under reduced pressure, and the remaining residue was separated by column chromatography (hexane / ethyl acetate) to give a solid 4- (3-chloro-4-fluorophenyl) -2,2-dimethyl-5- {4- 32 mg of (methylsulfonyl) phenyl} -3 ( 2H ) -furanone were obtained. mp: 162-164 o C. NMR: δ 1.58 (s, 6H), 3.09 (s, 3H), 7.13 (m, 2H), 7.40 (d, J = 6.6 Hz, 1H), 7.83 (d, J = 8.1 Hz, 2H), 7.97 (d, J = 8.1 Hz, 2H). IR (cm −1 ): 2930, 1700, 1587, 1503, 1404, 1317, 1150, 1068, 913, 771, 744.
    [820] Example 3
    [821] 2,2-dimethyl-4- (4-methoxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [822]
    [823] 4-Bromo-2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone (220 mg), 1,3-bis (diphenylphosphino) propane (24 mg) and palladium (II) acetate (6.1 mg) were dissolved in 30 ml of benzene, and a 2M aqueous sodium carbonate solution (0.22 ml) and 4-methoxybenzeneboronic acid (90 mg) were added dropwise. The reaction solution was refluxed for 24 hours. The solvent was then removed under reduced pressure, and the remaining residue was purified in a similar manner to the purification method of Example 2 to give a solid 2,2-dimethyl-4- (4-methoxyphenyl) -5- {4- (methyl 55 mg of sulfonyl) phenyl} -3 ( 2H ) -furanone was obtained. NMR: δ 1.56 (s, 6H), 3.07 (s, 3H), 3.83 (s, 3H), 6.92 (d, J = 8.7 Hz, 2H), 7.23 (d, J = 9.0 Hz, 2H), 7.89 ( dd, J = 8.7, 8.7 Hz, 4H). IR (cm -1 ): 2925, 1697, 1592, 1149, 1031, 912, 745.
    [824] Example 4
    [825] 2,2-dimethyl-4- (3-fluorophenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [826]
    [827] 4-bromo-2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone (170 mg) was dissolved in 30 ml of toluene and 10 ml of ethanol and stirred in a solution. , 25 mg of tetrakis (triphenylphosphine) palladium (0), 10 ml of saturated aqueous sodium bicarbonate solution and 100 mg of 3-fluorobenzeneboronic acid were added dropwise. The reaction solution was stirred at 90 ° C. for 12 hours. The solvent was then removed under reduced pressure and the remaining residue was extracted with water and dichloromethane. The organic layer was concentrated under reduced pressure, and the remaining residue was separated by column chromatography (hexane / ethyl acetate) to give a solid 2,2-dimethyl-4- (3-fluorophenyl) -5- {4- (methylsulfonyl 120 mg of) phenyl} -3 ( 2H ) -furanone was obtained. mp: 178-179 o C. NMR: δ 1.58 (s, 6H), 3.08 (s, 3H), 7.05 (m, 3H), 7.33 (m, 1H), 7.83 (d, J = 8.7 Hz, 2H) , 7.95 (d, J = 8.4 Hz, 2H). IR (cm −1 ): 3020, 1697, 1620, 1403, 1318, 1149, 958, 768. MS (FAB): 361 ( m + 1).
    [828] The title compound can also be prepared by the method described below: 2,2-dimethyl-4- (3-fluorophenyl) -5- {4- (methylthio) phenyl} -3 ( 2H ) 3.0 g of furanone (Example 166) were dissolved in 10 mL of oxone in 50 mL of THF, 50 mL of methanol and 50 mL of water. The reaction mixture was stirred at rt for 2 h. The solution was then concentrated under reduced pressure, and the remaining aqueous solution was extracted with 150 ml of methylene chloride. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The magnesium sulfate was removed by filtration, and the remaining filtrate was concentrated under reduced pressure. The remaining residue was recrystallized from methylene chloride / hexane to give 3.3 g of 2,2-dimethyl-4- (3-fluorophenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone. Obtained.
    [829] Another modification for the preparation of 2,2-dimethyl-4- (3-fluorophenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone is described as 2- (3 Fluorophenyl) -1- {4- (methylsulfonyl) phenyl} -ethanone as starting material was carried out as follows: 2- (3-fluorophenyl) -1- (4-methylsulfonyl Phenyl) -ethanone (1 g) was dissolved in 10 mL of THF, and 0.23 g of 95% sodium hydride was added at 0 ° C. to the stirred solution. The reaction solution was then stirred at the same temperature for 1 hour. 0.64 g of α- bromo-isobutyl acid cyanide was slowly added dropwise to the reaction mixture at 0 ° C. The reaction mixture was further stirred for 7 hours while raising the temperature to room temperature. 5 ml of water was added to stop the reaction. The mixture was concentrated under reduced pressure and then dissolved in 50 ml of water. The aqueous solution was extracted with ethyl acetate (100 mL). The organic layer was washed with brine, and then concentrated under reduced pressure. The remaining residue was purified by column chromatography (hexane / ethyl acetate) to give 2,2-dimethyl-4- (3-fluorophenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) 0.75 g of furanone were obtained.
    [830] Example 5
    [831] 4- (3-acetylphenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [832]
    [833] 4-bromo-2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone (170 mg) was dissolved in 30 ml of toluene and 10 ml of ethanol and stirred in a solution. Then, 25 mg of tetrakis (triphenylphosphine) paladione (0), 10 ml of saturated aqueous sodium carbonate solution and 130 ml of 3-acetylbenzeneboronic acid were added. The reaction solution was stirred at 90 ° C. for 12 hours. The solvent was then removed under reduced pressure and the remaining residue was extracted with water and dichloromethane. The organic layer was concentrated under reduced pressure, and the remaining residue was separated by column chromatography (hexane / ethyl acetate = 2: 1) to give a solid 4- (3-acetylphenyl) -2,2-dimethyl-5- {4- 100 mg of (methylsulfonyl) phenyl} -3 ( 2H ) -furanone were obtained. mp: 189-190 o C. NMR: δ 1.60 (s, 6H), 2.59 (s, 3H), 3.07 (s, 3H), 7.48 (m, 2H), 7.82 (d, J = 8.7 Hz, 2H) , 7.90 (m, 2H), 7.94 (d, J = 8.4 Hz, 2H). IR (cm -1 ): 1690, 1620, 1589, 1149, 958, 770.
    [834] Example 6
    [835] 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (3-nitrophenyl) -3 ( 2H ) -Furanone
    [836]
    [837] 4-bromo-2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone (170 mg) was dissolved in 30 ml of toluene and 10 ml of ethanol and stirred in a solution. , 25 mg of tetrakis (triphenylphosphine) palladium (0), 10 ml of saturated aqueous sodium carbonate solution and 120 mg of 3-nitrobenzeneboronic acid were added. The reaction solution was stirred at 90 ° C. for 12 hours. The solvent was removed under reduced pressure, and the remaining residue was extracted with water and dichloromethane (50 mL x 3). The organic layer was concentrated under reduced pressure, and the remaining residue was separated by column chromatography (hexane / ethyl acetate) to give a solid 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (3-nitro 100 mg of phenyl) -3 ( 2H ) -furanone were obtained. mp: 158-159 o C. NMR: δ 1.61 (s, 6H), 3.09 (s, 3H), 7.57 (t, J = 7.8 Hz, 1H), 7.64 (m, 1H), 7.81 (d, J = 9.0 Hz, 2H), 7.98 (d, J = 8.7 Hz, 2H), 8.19 (m, 2H). IR (cm -1 ): 2982, 1697, 1529, 1403, 1349, 1150, 959,770.
    [838] Example 7
    [839] 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- {4- (trifluoromethoxy) phenyl} -3 ( 2H ) -Furanone
    [840]
    [841] 4-bromo-2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone (150 mg) was dissolved in 15 ml of toluene and 5 ml of ethanol and stirred in a solution. Then, 30 mg of tetrakis (triphenylphosphine) paladione (0), 5 ml of saturated aqueous sodium carbonate solution and 100 mg of 4- (trifluoromethoxy) benzeneboronic acid were added. The reaction solution was stirred at 90 ° C. for 24 hours. The solvent was removed under reduced pressure and the remaining residue was extracted with water and dichloromethane. The organic layer was concentrated under reduced pressure, and the remaining residue was separated by column chromatography (hexane / ethyl acetate) to give a solid 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- {4- 60 mg of (trifluoromethoxy) phenyl} -3 ( 2H ) -furanone were obtained. mp: 118-120 o C. NMR: δ 1.58 (s, 6H), 3.08 (s, 3H), 7.20-7.26 (m, 2H), 7.31-7.34 (m, 2H), 7.82-7.85 (m, 2H ), 7.95-7.98 (m, 2 H). IR (cm −1 ): 2931, 1698, 1510, 1387, 1258, 1150, 960, 846, 770.
    [842] Example 8
    [843] 2,2-dimethyl-4- (3,4-methylenedioxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [844]
    [845] 4-bromo-2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone (200 mg) was dissolved in 30 ml of toluene and 10 ml of ethanol and stirred in a solution. Then, 25 mg of tetrakis (triphenylphosphine) paladione (0), 10 ml of saturated aqueous sodium carbonate solution and 150 mg of (3,4-methylenedioxy) benzeneboronic acid were added. The reaction solution was stirred at 90 ° C. for 12 hours. The solvent was removed under reduced pressure and the remaining residue was extracted with water and dichloromethane. The organic layer was concentrated under reduced pressure, and the residue was separated by column chromatography (hexane / ethyl acetate) to give a solid 2,2-dimethyl-4- (3,4-methylenedioxyphenyl) -5- {4- 100 mg of (methylsulfonyl) phenyl} -3 ( 2H ) -furanone were obtained. mp: 178-179 o C. NMR: δ 1.60 (s, 6H), 3.07 (s, 3H), 5.99 (s, 2H), 6.74 (m, 2H), 6.84 (d, J = 8.7 Hz, 1H) , 7.87 (d, J = 8.7 Hz, 2H), 7.94 (d, J = 8.7 Hz, 2H). IR (cm −1 ): 1697, 1503, 1404, 1245, 1148, 959, 770.
    [846] Example 9
    [847] 2,2-dimethyl-4- {4- (3-fluoro-4-phenyl) phenyl} -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [848]
    [849] 200 mg of 4-bromo-2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone was prepared by {(3- Combined with 170 mg of fluoro-4-phenyl) benzene} boronic acid to yield solid 2,2-dimethyl-4-{(3-fluoro-4-phenyl) phenyl} -5- {4- (methylsulfonyl 110 mg of) -phenyl} -3 ( 2H ) -furanone were obtained. mp: 163-164 o C. NMR: δ 1.60 (s, 6H), 3.09 (s, 3H), 7.13 (m, 2H), 7.41 (m, 2H), 7.45 (m, 2H), 7.57 (m, 2H), 7.91 (d, J = 8.7 Hz, 2H), 7.98 (d, J = 8.7 Hz, 2H). IR (cm −1 ): 3020, 1698, 1621, 1402, 1319, 1258, 1148, 957, 770.
    [850] Example 10
    [851] 4- (4-acetylphenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [852]
    [853] 200 mg of 4-bromo-2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone (200 mg) in a similar manner to the synthesis method in Example 2 Solid 4- (4-acetylphenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone in combination with 104 mg of (4-acetylbenzene) boronic acid 55 mg was obtained. mp: 164-167 o C. NMR: δ 1.60 (s, 6H), 2.32 (s, 3H), 3.08 (s, 3H), 7.39-7.42 (m, 2H), 7.81-7.84 (m, 2H), 7.94-7.98 (m, 4 H). IR (cm -1 ): 1696, 1685, 1618, 1386, 1318, 1150, 960, 770.
    [854] Example 11
    [855] 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [856]
    [857] 4-bromo-2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone (300 mg) was dissolved in 30 ml of toluene and 10 ml of ethanol and stirred in a solution. , 25 mg of tetrakis (triphenylphosphine) palladium (0), 10 ml of 2M aqueous sodium carbonate solution and 200 mg of (3,5-difluorobenzene) boronic acid were added. The reaction solution was stirred at 90 ° C. for 12 hours. After removing the solvent under reduced pressure, the remaining residue was extracted with water and dichloromethane. The organic layer was concentrated under reduced pressure, and the remaining residue was separated by column chromatography (hexane / ethyl acetate) to obtain solid 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {4-. 200 mg of (methylsulfonyl) phenyl} -3 ( 2H ) -furanone were obtained. mp: 141-142 o C. NMR: δ 1.60 (s, 6H), 3.08 (s, 3H), 3.95 (s, 3H), 6.92 (m, 3H), 7.88 (d, J = 8.7 Hz, 2H) , 7.93 (d, J = 8.7 Hz, 2H). IR (cm- 1 ): 1695, 1611, 1516, 1316, 1270, 1123, 1023, 858, 769. MS (FAB): 379 ( m + 1).
    [858] Further, 18 g of 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {4- (methylthio) -phenyl} -3 ( 2H ) -furanone (Example 173), 45 g of oxone and 300 ml of THF, 300 ml of ethanol and 300 ml of water were reacted in a manner similar to that of Example 4 to give 4- (3,5-difluorophenyl) -2,2-dimethyl-5 19.5 g of-{4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone were obtained.
    [859] Example 12
    [860] 2,2-dimethyl-4- (3,5-dimethyl-4-methoxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [861]
    [862] 300 mg of 4-bromo-2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone was prepared in a similar manner to that in Example 2 (3,5- Combined with 250 mg of dimethyl-4-methoxybenzene) boronic acid, solid 2,2-dimethyl-4- (3,5-dimethyl-4-methoxyphenyl) -5- {4- (methylsulfonyl) 60 mg of phenyl} -3 ( 2H ) -furanone were obtained. mp: 130-131 o C. NMR: δ 1.56 (s, 6H), 2.26 (s, 6H), 3.07 (s, 3H), 3.75 (s, 3H), 6.91 (s, 2H), 7.87 (d, J = 8.7 Hz, 2H), 7.92 (d, J = 8.7 Hz, 2H). IR (cm- 1 ): 2929, 1697, 1591, 1399, 1319, 1149, 1135, 771.
    [863] Example 13
    [864] 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (1-naphthyl) -3 ( 2H ) -Furanone
    [865]
    [866] 200 mg of 4-bromo-2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone was obtained by naphthalene-1-borone in a similar manner to that in Example 2. Combination with 114 mg of acid afforded solid 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (1-naphthyl) -3 ( 2H ) -furanone. mp: 194-195 o C. NMR: δ 1.67 (s, 3H), 1.71 (s, 3H), 2.97 (s, 3H), 7.33-7.43 (m, 2H), 7.48-7.60 (m, 2H), 7.51-7.52 (m, 1 H), 7.66-7.69 (m, 2H), 7.76-7.78 (m, 2H), 7.90-7.94 (m, 2H). IR (cm- 1 ): 1698, 1404, 1318, 1149, 1092, 772.
    [867] Example 14
    [868] 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- {3- (trifluoromethyl) phenyl) -3 ( 2H ) -Furanone
    [869]
    [870] 200 mg of 4-bromo-2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone was prepared in a similar manner to the synthesis method of Example 2 (3-tri Combined with 150 mg of fluoromethylbenzene) boronic acid, solid 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (3-trifluoromethylphenyl) -3 ( 2H )- 100 mg of furanone was obtained. mp: 115-116 o C. NMR: δ 1.60 (s, 6H), 3.08 (s, 3H), 7.49 (m, 2H), 7.60 (m, 2H), 7.82 (d, J = 8.7 Hz, 2H) , 7.96 (d, J = 9.0 Hz, 2H). IR (cm <-1> ): 1697, 1624, 1385, 1327, 1124, 959, 770. MS (FAB): 411 ( m + 1).
    [871] In addition, 1.5 g of 2,2-dimethyl-5- {4- (methylthio) phenyl} -4- {3- (trifluoromethyl) phenyl} -3 ( 2H ) -furanone (Example 169), 4.5 g of oxone was reacted in 50 ml of THF, 50 ml of ethanol and 50 ml of water by the method used in the alternative method in Example 4, to obtain 1.28 g of the title compound.
    [872] Example 15
    [873] 4- (2-benzo [b] thienyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [874]
    [875] 200 mg of 4-bromo-2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone was prepared in a similar manner to Example 2 (2-benzo [b] thienyl Combined with 125 mg of boronic acid to form solid 4- (2-benzo [b] thienyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone 60 mg were obtained. mp: 204-206 o C. NMR: δ 1.61 (s, 6H), 3.11 (s, 3H), 7.32-7.43 (m, 4H), 7.51-7.53 (m, 1H), 7.74-7.84 (m, 2H ), 8.01 (s, 2 H). IR (cm <-1> ): 1702, 1620, 1382, 1147, 957, 750.
    [876] Example 16
    [877] 4- (2-benzo [b] furanyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [878]
    [879] 200 mg of 4-bromo-2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone was prepared in a similar manner to the synthesis method of Example 2 (2-benzo reacted with 107 mg of [b] furan) boronic acid to give solid 4- (2-benzo [b] furanyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H 15 mg of) -furanone were obtained. mp: 140-141 ° C. NMR: δ 1.60 (s, 6H), 3.13 (s, 3H), 7.22-7.35 (m, 4H), 7.60-7.63 (m, 1H), 8.06 (m, 4H). IR (cm- 1 ): 1703, 1538, 1406, 1317, 1149, 958, 752.
    [880] Example 17
    [881] 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (3-thienyl) -3 ( 2H ) -Furanone
    [882]
    [883] Thiophen-3 in 200 mg of 4-bromo-2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone in a similar manner to the synthesis in Example 2 Combined with 100 mg of boronic acid to give 10 mg of solid 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (3-thienyl) -3 ( 2H ) -furanone It was. NMR: δ 1.56 (s, 6H), 3.09 (s, 3H), 6.92-6.93 (m, 1H), 7.32-7.35 (m, 1H), 7.51-7.52 (m, 1H), 7.90-7.93 (m, 2H), 7.97-8.00 (m, 2H).
    [884] Example 18
    [885] 2,2-dimethyl-4- (2-furanyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [886]
    [887] Step 1: 2,2-dimethyl-4-iodine-5- {4- (methylsulfonyl) phenyl} -3 ( 2H) -Production of Furanone
    [888]
    [889] In a similar manner to Step 5 of Example 1, 2,2-dimethyl- prepared by oxidation of 2,2-dimethyl-5- {4- (methylthio) phenyl} -3 ( 2H ) -furanone with oxone 25 g of 5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone were dissolved in 400 ml of carbon tetrachloride and 100 ml of chloroform, followed by [bis (trifluoroacetoxyl) iodine] benzene [BTI] 25 g and 15 g of iodine were added. After the mixture was stirred at room temperature for 3 hours, the reaction was stopped by adding saturated aqueous sodium thiosulfate solution to the reaction until the intrinsic color of iodine disappeared. The solution was extracted with chloroform (500 mL x 3), and the organic layer was concentrated under reduced pressure. The remaining residue was recrystallized from hexane and ethyl acetate to give 35 g of 2,2-dimethyl-4-iodine-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone. mp: 184-185 o C. NMR: δ 1.55 (s, 6H), 3.12 (s, 3H), 8.12 (d, J = 8.7 Hz, 2H), 8.40 (d, J = 8.7 Hz, 2H).
    [890] Step 2: 2,2-dimethyl-4- (2-furanyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H) -Production of Furanone
    [891] 250 mg of 2,2-dimethyl-4-iodine-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone was mixed with 86 mg of furan-2-boronic acid in a similar manner to Example 2. The reaction was carried out to obtain 47 mg of solid 2,2-dimethyl-4- (2-furanyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone. NMR: δ 1.56 (s, 6H), 3.11 (s, 3H), 6.51 (m, 1H), 6.89 (d, J = 3.6 Hz, 1H), 7.37 (d, J = 3.6 Hz, 1H), 7.97 ( m, 4H). IR (cm- 1 ): 2989, 1703, 1409, 1317, 1148, 959, 771.
    [892] Example 19
    [893] 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (3-pyridyl) -3 ( 2H ) -Furanone
    [894]
    [895] 4-bromo-2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone (200 mg) was dissolved in 15 ml of toluene and 5 ml of ethanol and stirred in a solution. , 27 mg of tris (dibenzylideneacetone) dipalladium (0) -chloroform addition product, 17 mg of triphenyl phosphine, 5 mL of 2M aqueous sodium carbonate solution and lithium 3-trimethylpyridinium boronate (200 mg) were added. The reaction solution was stirred at 90-100 o C for 24 hours. The solvent was then removed under reduced pressure. The remaining residue was extracted with water and dichloromethane (100 mL x 3). The organic layer was concentrated under reduced pressure, and the remaining residue was separated by column chromatography (hexane / ethyl acetate) to give a solid 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (3- 110 mg of pyridyl) -3 ( 2H ) -furanone was obtained. mp: 164-166 o C. NMR: δ 1.60 (s, 6H), 3.09 (s, 3H), 7.38-7.42 (m, 1H), 7.76-7.79 (m, 1H), 7.80-7.83 (m, 2H ), 7.96-7.99 (m, 2H), 8.42-8.49 (m, 1H), 8.56-8.61 (m, 1H). IR (cm- 1 ): 1698, 1386, 1316, 1149, 1061, 961, 772.
    [896] Example 20
    [897] 2,2-dimethyl-4- {4- (1- N -Methylpyrazolyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [898]
    [899] To a solution in which 2,2-dimethyl-4-iodine-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone (445 mg) was dissolved in 50 ml of toluene and 15 ml of ethanol and stirred, 25 mg of tetrakis (triphenylphosphine) palladium (0), 15 mL of 2M aqueous sodium carbonate solution and 547 mg of {4- (1-N-methylpyrazolyl)}-trimethylboronic acid lithium salt were added. The reaction solution was stirred at 90 ° C. for 12 hours. The solvent was then removed under reduced pressure. The remaining residue was extracted with water and dichloromethane (50 mL x 3). The organic layer was concentrated under reduced pressure, and the remaining residue was separated by column chromatography (hexane / ethyl acetate) to give a solid 2,2-dimethyl-4- {4- (1-N-methylpyrazolyl)}-5- 290 mg of {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone were obtained. mp: 114-115 o C. NMR: δ 1.54 (s, 6H), 3.10 (s, 3H), 3.94 (s, 3H), 7.34 (s, 1H), 7.34 (s, 1H), 7.99-8.06 ( m, 4H). IR (cm -1 ): 2930, 1700, 1538, 1314, 1148, 884, 771.MS (FAB): 347 ( m +1)
    [900] Example 21
    [901] 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (4-pyrazolyl) -3 ( 2H ) -Furanone
    [902]
    [903] Step 1: Preparation of 4-bromo-1-N-tritylpyrazole
    [904] A mixture of 0.5 g of 4-bromopyrazole and 1.43 g of tritylchloride in 30 ml of pyridine was stirred under reflux for 18 hours. The pyridine was removed under reduced pressure and the remaining residue was purified by silica column chromatography (ethyl acetate / hexane = 1: 1) to give 1.32 g of 4-bromo-1-N-tritylpyrazole.
    [905] Step 2: Preparation of {4- (1-N-tritylpyrazole)}-trimethyl boronic acid salt
    [906] 1.4 mL of 2M butyllithium in hexanes was added dropwise to a solution obtained by dissolving 4-bromo-1-N-tritylpyrazole in -78 ° C. in 30 mL of anhydrous THF and stirring. Then, the reaction mixture was stirred for 30 minutes, and then 0.76 ml of triisopropylboronic acid salt was added thereto. After the reaction mixture was stirred for an additional hour, the reaction was stopped by adding 20 ml of methanol. The solvent was removed under reduced pressure, and the resulting salt was used in the next step without further purification.
    [907] Step 3: 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- {4- (1-N-tritylpyrazole)}-3 ( 2H) -Production of Furanone
    [908] 300 mg of 2,2-dimethyl-4-iodine-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone was dissolved in 50 ml of toluene and 15 ml of ethanol, followed by tetrakis (triphenyl 25 mg of phosphine) palladium (0), 15 mL of 2M aqueous sodium carbonate solution and 480 mg of {4- (1-N-tritylpyrazolyl)}-trimethylboronic acid lithium salt in the previous step were added. The reaction mixture was stirred at 90 ° C. for 12 hours. The reaction mixture was purified in a similar manner to the purification method in Example 2 to give 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- {4- (1-N-tritylpyra Sol)}-3 ( 2H ) -furanone was obtained 120 mg.
    [909] Step 4: 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (4-pyrazolyl) -3 ( 2H) -Production of Furanone
    [910] 120 mg of 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- {4- (1-N-tritylpyrazolyl)}-3 ( 2H ) -furanone, p-toluene It was stirred for 3 hours in 23 ml of methanol added with 36 mg of sulfonic acid. The methanol was then removed under reduced pressure and the remaining residue was diluted with 30 mL of water. The aqueous layer was extracted with dichloromethane (30 mL x 3), and the organic layer was concentrated under reduced pressure. The remaining residue was purified by column chromatography (hexane / ethyl acetate = 1: 4) to give 2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (4-pyrazolyl) -3 60 mg ( 2H ) -furanone was obtained. NMR: δ 1.56 (s, 6H), 3.11 (s, 3H), 7.88 (s, 2H), 8.05 (m, 5H). IR (cm- 1 ): 3325, 1702, 1408, 1316, 1148, 913.
    [911] Example 22
    [912] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (4-fluorophenyl) -3 ( 2H ) -Furanone
    [913]
    [914] Step 1: 2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -3 ( 2H) -Production of Furanone
    [915]
    [916] M -chloroper in a solution obtained by dissolving 2,2-dimethyl-5- {4- (methylthio) phenyl} -3 ( 2H ) -furanone (10 g) in 200 ml of dichloromethane at 0 ° C. 4.8 g of oxybenzoic acid ( m- CPBA) was dissolved in 50 ml of dichloromethane and slowly added dropwise. The reaction mixture was further stirred at 0 ° C. for 2 hours, and then the reaction solution was concentrated under reduced pressure. The remaining residue was extracted with water and dichloromethane (50 mL x 3) and then washed with aqueous sodium carbonate solution. After concentration of the organic layer, the crude product was purified by column chromatography (hexane / ethyl acetate) to give a solid 2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone 7.5 g were obtained. mp: 108-109 o C. NMR: δ 1.51 (s, 6H), 2.78 (s, 3H), 6.06 (s, 1H), 7.78 (d, J = 8.4 Hz, 2H), 8.02 (d, J = 8.4 Hz, 2H). IR (cm- 1 ): 2925, 1697, 1603, 1558, 1173, 1087, 1049.
    [917] Step 2: 2,2-dimethyl-4-iodine-5- {4- (methylsulfinyl) phenyl} -3 ( 2H) -Production of Furanone
    [918]
    [919] 6 g of 2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone was dissolved in 200 ml of carbon tetrachloride and 100 ml of chloroform and stirred in a solution of [bis (trifluoro 5.15 g of acetoxy) iodine] benzene (BTI) and 6.5 g of iodine were added, and the reaction solution was stirred at room temperature. After 4 hours, the reaction was stopped by addition of saturated aqueous sodium thiosulfate solution until the intrinsic color of iodine disappeared. The solution was stopped and extracted with water and dichloromethane (100 mL x 3). The organic layer was concentrated under reduced pressure, and the remaining crude product was recrystallized from hexane / ethyl acetate to give 4.5 g of 2,2-dimethyl-4-iodine-5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone. Obtained. NMR: δ 1.53 (s, 6H), 2.79 (s, 3H), 7.81 (d, J = 8.1 Hz, 2H), 8.38 (d, J = 8.1 Hz, 2H). IR (cm −1 ): 2975, 2929, 1699, 1595, 1404, 1319, 1150, 969, 766, 552.
    [920] Step 3: 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4-iodine-3 2H) -Production of Furanone
    [921]
    [922] 30 ml of anhydrous trifluoroacetic acid (TFAA) 1.11 g of 2,2-dimethyl-4-iodine-5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone at 0 o C for 2 hours Reacted with After the volatile solvent was removed under reduced pressure, the remaining residue was dissolved in 50 mL of 1: 1 methanol / triethylamine. The solvent was removed again under reduced pressure. The remaining residue was dissolved in 30 mL of carbon tetrachloride, then 40 mL of acetic acid saturated with chlorine was added slowly at 0 ° C. After the reaction solution was stirred at 0 ° C. for 20 minutes, the reaction solvent and unreacted chlorine were removed under reduced pressure. The remaining residue was dissolved in 30 ml of toluene and the toluene was removed under reduced pressure. The residue remaining in 40 ml of THF was reacted with 3 ml of ammonia water at 0 ° C. for 30 minutes. The reaction solution was concentrated under reduced pressure, and the remaining residue was diluted with 30 mL of water. The aqueous solution was extracted with dichloromethane (30 mL x 3). The organic layer was concentrated under reduced pressure, and then purified by column chromatography (hexane / ethyl acetate = 3: 2) to give solid 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4-iodine-. 450 mg of 3 ( 2H ) -furanone were obtained. mp: 179-180 o C. NMR: δ 1.50 (s, 6H), 5.63 (br. s, 2H), 8.05 (dd, J = 9.0,1.5 Hz, 2H), 8.29 (dd, J = 9.0, 5.7 Hz, 2H). IR (cm −1 ): 3367, 3261, 2985, 1684, 1582, 1405, 1188, 913. MS (FAB): 393 ( m + 1).
    [923] Step 4: 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (4-fluorophenyl) -3 ( 2H) -Production of Furanone
    [924] Tetrakis in a solution in which 100 mg of 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4-iodine-3 (2H) -furanone was dissolved in 15 ml of toluene and 5 ml of ethanol and stirred. 34 mg of (triphenylphosphine) palladium (0), 5 ml of a 2M aqueous sodium carbonate solution and 80 mg of (4-fluorobenzene) boronic acid were added. The reaction solution was stirred at 95 ° C. for 24 hours, and then the solvent was removed under reduced pressure. The remaining residue was extracted with 30 mL of water and dichloromethane (30 mL x 3). The organic layer was dried over anhydrous magnesium sulfate. After hydrated magnesium sulfate was removed by filtration, the filtrate was concentrated under reduced pressure. The remaining crude product was purified by column chromatography (hexane / ethyl acetate = 1: 1) to give solid 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (4-fluorophenyl 40 mg of) -3 ( 2H ) -furanone was obtained. mp: 162-163 o C. NMR: δ 1.57 (s, 6H), 4.93 (br. s, 2H), 7.08 (d, J = 8.7 Hz, 2H), 7.25 (t, J = 8.7 Hz, 2H) , 7.78 (d, J = 8.7 Hz, 2H), 7.92 (d, J = 8.7 Hz, 2H). IR (cm- 1 ): 3348, 3263, 1685, 1589, 1341, 1219, 1163.
    [925] Example 23
    [926] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {3- (trifluoromethyl) phenyl} -3 ( 2H ) -Furanone
    [927]
    [928] Tetrakis in a solution in which 100 mg of 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4-iodine-3 ( 2H ) -furanone was dissolved in 15 ml of toluene and 5 ml of ethanol and stirred. 30 mg of (triphenylphosphine) palladium (0), 5 ml of 2M aqueous sodium carbonate solution and 100 mg of 3- (trifluoromethyl) benzeneboronic acid were added. The mixture was stirred at 95 o C for 24 h. The reaction mixture was purified in a similar manner to Step 4 of Example 22, to obtain 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {3- (trifluoromethyl) phenyl} -3 35 mg ( 2H ) -furanone was obtained. mp: 129-130 ° C. NMR: δ 1.59 (s, 6H), 4.93 (br. s, 2H), 7.48 (m, 2H), 7.59 (m, 2H), 7.76 (d, J = 8.7 Hz, 2H), 7.93 (d, J = 9.0 Hz, 2H). IR (cm- 1 ): 3343, 3265, 1691, 1593, 1329, 1262.
    [929] Example 24
    [930] 5- {4- (aminosulfonyl) phenyl} -4- {3,4- (dimethoxy) phenyl} -2,2-dimethyl-3 ( 2H ) -Furanone
    [931]
    [932] Tetrakis in a solution in which 150 mg of 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4-iodine-3 ( 2H) -furanone was dissolved in 15 ml of toluene and 5 ml of ethanol and stirred 20 mg of (triphenylphosphine) palladium (0), 5 ml of 2M aqueous sodium carbonate solution and 100 mg of 3,4- (dimethoxy) benzeneboronic acid were added dropwise. The reaction mixture was stirred at 95 ° C. for 24 hours. The reaction was purified in a similar manner to step 4 of Example 22 to give solid 5- {4- (aminosulfonyl) phenyl} -4- {3,4- (dimethoxy) phenyl} -2,2-dimethyl- 60 mg of 3 ( 2H ) -furanone were obtained. mp: 213-214 o C. NMR: δ 1.57 (s, 6H), 3.81 (s, 3H), 3.90 (s, 3H), 4.87 (br s, 2H), 6.86 (m, 3H), 7.81 (d , J = 8.4 Hz, 2H), 7.91 (d, J = 8.7 Hz, 2H). IR (cm -1 ): 3339, 3248, 1694, 1404, 1259, 1159, 1024, 604.
    [933] Example 25
    [934] 4- (3-acetylphenyl) -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 2H ) -Furanone
    [935]
    [936] 150 mg of 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4-iodine-3 ( 2H ) -furanone was prepared in a similar manner to step 4 of Example 22 with (3-acetylbenzene) boron Reaction with 75 mg of acid gave 40 mg of solid 4- (3-acetylphenyl) -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 2H ) -furanone. mp: 217-218 o C. NMR: δ 1.57 (s, 6H), 2.58 (s, 3H), 4.89 (br s, 2H), 7.48 (m, 2H), 7.78 (m, 2H), 7.91 (m , 4H). IR (cm −1 ): 3340, 3233, 1682, 1558, 1162, 801, 751, 679, 654, 604. MS (FAB): 393 ( m + 1).
    [937] Example 26
    [938] 4- {3-N- (acetylamino) phenyl} -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 2H ) -Furanone
    [939]
    [940] 60 mg of 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4-iodine-3 ( 2H ) -furanone were prepared in a similar manner to step 4 of Example 22 using {3-N- ( Acetylamino) benzene} boronic acid was reacted with 35 mg of solid 4- {3-N- (acetylamino) phenyl} -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 25 mg of 2H ) -furanone were obtained. mp: 225-227 o C. NMR: δ 1.62 (s, 6H), 2.04 (s, 3H), 4.82 (br s, 2H), 7.46 (m, 3H), 7.53 (m, 1H), 7.68 (m , 4H). IR (cm- 1 ): 3325, 2926, 1698, 1558, 1437, 1119.
    [941] Example 27
    [942] 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {3,4- (methylenedioxy) phenyl} -3 ( 2H ) -Furanone
    [943]
    [944] 120 mg of 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4-iodine-3 ( 2H ) -furanone was added to 3,4- (methylenedi in a similar manner to step 4 of Example 22. Reaction with 100 mg of oxy) benzeneboronic acid to yield solid 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {3,4- (methylenedioxy) phenyl} -3 ( 2H 40 mg of) -furanone were obtained. mp: 178-179 o C. NMR: δ 1.56 (s, 6H), 4.89 (br s, 2H), 5.99 (s, 2H), 6.74 (m, 2H), 6.83 (m, 1H), 7.82 (d , J = 9.0 Hz, 2H), 7.92 (d, J = 9.0 Hz, 2H). IR (cm -1 ): 3237, 1682, 1338, 1245, 1164.
    [945] Example 28
    [946] 5- {4- (aminosulfonyl) phenyl} -4- (2-benzo [b] thienyl) -2,2-dimethyl-3 ( 2H ) -Furanone
    [947]
    [948] 200 mg of 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4-iodine-3 ( 2H ) -furanone were prepared in a similar manner to step 4 of Example 22 (2-benzo [b] In combination with 109 mg of thiophene) boronic acid, solid 5- {4- (aminosulfonyl) phenyl} -4- (2-benzo [b] thienyl) -2,2-dimethyl-3 ( 2H )- 45 mg of furanone was obtained. mp: 120-121 o C. NMR: δ 1.60 (s, 3H), 4.89 (br s, 2H), 7.36 (m, 2H), 7.50 (m, 1H), 7.75 (m, 2H), 7.97 (m , 4H). IR (cm −1 ): 3350, 3210, 1650, 1530, 1320, 1158, 803, 743. MS (FAB): 400 ( m + 1).
    [949] Example 29
    [950] 5- {4- (aminosulfonyl) phenyl} -4- (3-biphenyl) -2,2-dimethyl-3 ( 2H ) -Furanone
    [951]
    [952] 200 mg of 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4-iodine-3 ( 2H ) -furanone was prepared in a similar manner to step 4 of Example 22 with (3-phenylbenzene) boron Reaction with 120 mg of acid gave 40 mg of solid 5- {4- (aminosulfonyl) phenyl} -4- (3-biphenyl) -2,2-dimethyl-3 ( 2H ) -furanone. mp: 160-161 o C. NMR: δ 1.57 (s, 6H), 4.86 (br s, 2H), 7.23 (m, 1H), 7.34 (m, 1H), 7.44 (m, 3H), 7.56 (m , 4H), 7.84 (d, J = 8.7 Hz, 2H), 7.91 (d, J = 8.7 Hz, 2H). IR (cm- 1 ): 3249, 1681, 1614, 1345, 1161.
    [953] Example 30
    [954] 5- {4- (aminosulfonyl) phenyl} -4- (2-benzo [b] furanyl) -2,2-dimethyl-3 ( 2H ) -Furanone
    [955]
    [956] 200 mg of 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4-iodine-3 ( 2H ) -furanone were prepared in the same manner as in step 4 of Example 22, with benzo [b] furan-2 In combination with 99 mg of boronic acid, solid 5- {4- (aminosulfonyl) phenyl} -4- (2-benzo [b] furanyl) -2,2-dimethyl-3 ( 2H ) -furanone 45 mg was obtained. mp: 143-145 ° C. NMR: δ 1.60 (s, 6H), 4.92 (br s, 2H), 7.23 (m, 3H), 7.72 (m, 2H), 8.02 (m, 4H). IR (cm −1 ): 3384, 3245, 1698, 1510, 1253, 1161, 793.
    [957] Example 31
    [958] 2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4-phenyl-3 ( 2H ) -Furanone
    [959]
    [960] Step 1: Preparation of 4-methyl-1- {4- (methylthio) phenyl} -2-hexine-1,4-diol
    [961]
    [962] To a solution stirred by dissolving 3-methyl-1-pentin-3-ol (23.3 g) in 150 mL of dry THF under -78 ° C. argon atmosphere, 130 mL of 2.5M butyllithium in hexane was mixed for 20 minutes. Added dropwise. The reaction solution was further stirred for 20 minutes, and then 16 ml of 4-methylthiobenzaldehyde was added dropwise. After further stirring for 2 hours, the reaction was stopped by adding 200 ml of diluted aqueous hydrochloric acid solution. After the reaction solvent was removed under reduced pressure, the remaining aqueous solution was extracted with dichloromethane (100 mL x 3). The organic layer was concentrated under reduced pressure, and the remaining residue was purified by column chromatography (hexane / ethyl acetate = 1: 1) to give 4-methyl-1- {4- (methylthio) phenyl} -2-hexyne-1 as an oil. 30 g of 4-diol were obtained. NMR: δ1.05 (t, J = 7.5 Hz, 3H), 1.51 (s, 3H), 1.73 (m, 2H), 2.18 (s, 1H), 2.50 (s, 3H), 5.49 (s, 1H) , 7.26 (d, J = 8.7 Hz, 2H), 7.45 (d, J = 8.7 Hz, 2H). IR (cm- 1 ): 3348, 2974, 2930,1492, 1092, 983, 795, 523.
    [963] Step 2: Preparation of 4-hydroxy-4-methyl-1- {4- (methylthio) phenyl} -2-hexyn-1-one
    [964]
    [965] After dissolving 9.9 g of 4-methyl-1- {4- (methylthio) phenyl} -2-hexine-1,4-diol in 200 ml of dichloromethane, 15 g of pyridinium dichromate (PDC) and celite 15 g was added. After the suspension was stirred overnight at room temperature, the insoluble material was filtered off with florisil. The filtrate was purified by column chromatography (hexane / ethyl acetate = 4/1) to give 5.34 g of 4-hydroxy-4-methyl-1- {4- (methylthio) phenyl} -2-hexyn-1-one. Obtained. NMR: δ1.13 (t, J = 7.5 Hz, 3H), 1.62 (s, 3H), 1.85 (q, J = 7.8 Hz, 2H), 2.54 (s, 3H), 7.28 (d, J = 8.7 Hz , 2H), 8.01 (d, J = 8.7 Hz, 2H). IR (cm- 1 ): 3427, 2974, 1588, 1095, 914, 745.
    [966] Step 3: 2-ethyl-2-methyl-5- {4- (methylthio) phenyl} -3 ( 2H) -Production of Furanone
    [967]
    [968] 5.34 g of 4-hydroxy-4-methyl-1- {4- (methylthio) phenyl} -2-hexyn-1-one are dissolved in 200 ml of ethanol and then 3 ml of diethylamine diluted with 50 ml of ethanol. Was added dropwise. The reaction solution was stirred at room temperature for 4 hours, and then the solvent was removed under reduced pressure. The remaining residue was extracted with water and dichloromethane (100 mL x 3). The crude 2-ethyl-2-methyl-5- {4- (methylthio) phenyl} -3 ( 2H ) -furanone crude product obtained by concentrating the organic layer was used for the next step of the reaction without purification.
    [969] Step 4: 2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H) -Production of Furanone
    [970]
    [971] The 2-ethyl-2-methyl-5- {4- (methylthio) phenyl} -3 ( 2H ) -furanone crude product from the previous step 3 was dissolved in 50 mL of ethanol, 50 mL of THF and 50 mL of water. , 10 g of oxone was added thereto. After stirring the reaction mixture overnight at room temperature, the insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The remaining aqueous layer was extracted with dichloromethane (100 mL x 1 and 50 mL x 2). The organic layer was concentrated under reduced pressure, and the residue was purified by column chromatography (hexane / ethyl acetate = 2: 1) to give 2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3. 4.5 g of ( 2H ) -furanone were obtained. NMR: δ 0.89 (t, J = 7.2 Hz, 3H), 1.48 (s, 3H), 1.91 (q, J = 7.2 Hz, 2H), 3.11 (s, 3H), 6.13 (s, 1H), 8.07 ( m, 4H).
    [972] Step 5: 4-bromo-2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H) -Production of Furanone
    [973]
    [974] 4.5 g of 2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone was dissolved in 100 ml of carbon tetrachloride, followed by acetic acid (3 ml) and bromine (1 ml). Was added. The reaction solution was stirred at room temperature for 1 hour. The reaction was stopped by addition of saturated aqueous sodium thiosulfate solution until the intrinsic color of bromine disappeared. The reaction solution was extracted with dichloromethane (30 mL x 3). The organic layer was concentrated under reduced pressure, and the remaining residue was purified by column chromatography (hexane / ethyl acetate = 1: 1) to give 4-bromo-2-ethyl-2-methyl-5- {4- (methylsulfonyl 4 g)) phenyl} -3 ( 2H ) -furanone was obtained. NMR: δ 0.91 (t, J = 7.2 Hz, 3H), 1.52 (s, 3H), 1.95 (qd, J = 7.2, 3.0 Hz, 2H), 3.11 (s, 3H), 8.11 (d, J = 8.7 Hz, 2H), 8.41 (d, J = 8.7 Hz, 2H). IR (cm- 1 ): 2928, 1703, 1583, 1316, 1160, 552.
    [975] Step 6: 2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4-phenyl-3 ( 2H) -Production of Furanone
    [976] 4-bromo-2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone (200 mg) was dissolved in 15 ml of toluene and stirred in a solution. 40 mg of kiss (triphenylphosphine) palladium (0), 5 ml of 2M aqueous sodium carbonate solution and 100 mg of benzeneboronic acid were added. The reaction solution was stirred for 12 hours while refluxing. The reaction solvent was evaporated under reduced pressure. The remaining residue was extracted with water and dichloromethane (30 mL x 3). The organic layer was concentrated under reduced pressure. The remaining crude mixture was purified by column chromatography (hexane / ethyl acetate = 2: 1) to give 2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4-phenyl-3 as a solid. 60 mg ( 2H ) -furanone was obtained. mp: 115-117 o C. NMR: δ 0.96 (t, J = 7.5 Hz, 3H), 1.55 (s, 3H), 1.97 (q, J = 7.5 Hz, 2H), 3.07 (s, 3H), 7.37 (m, 5H), 7.85 (d, J = 8.7 Hz, 2H), 7.93 (d, J = 8.7 Hz, 2H). IR (cm- 1 ): 2928, 1697, 1620, 1403, 1318, 1149, 959, 769, 552.
    [977] Example 32
    [978] 4- (3,5-difluorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [979]
    [980] 4-bromo-2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone (200 mg) was dissolved in 15 ml of toluene and 5 ml of ethanol and stirred To the solution, 34 mg of tetrakis (triphenylphosphine) palladium (0), 5 ml of 2M aqueous sodium carbonate solution and 110 mg of 3,5-difluorobenzeneboronic acid were added dropwise. The reaction solution was stirred at 95 ° C. for 12 hours. After evaporation of the reaction solvent under reduced pressure, the remaining residue was extracted with 50 mL of water and dichloromethane (30 mL x 3). The organic layer was concentrated under reduced pressure, and the remaining crude mixture was purified by column chromatography (hexane / ethyl acetate = 2: 1) to obtain solid 4- (3,5-difluorophenyl) -2-ethyl-2-. 80 mg of methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone were obtained. mp: 122-124 o C. NMR: δ 0.95 (t, J = 7.5 Hz, 3H), 1.54 (s, 3H), 1.97 (m, 2H), 3.10 (s, 3H), 6.81 (m, 3H) , 7.84 (d, J = 8.7 Hz, 2H), 7.99 (d, J = 8.4 Hz, 2H). IR (cm -1 ): 2975, 2928, 1698, 1627, 1321, 1150, 990, 769, 552.
    [981] Example 33
    [982] 4- {3- (N-acetylamino) phenyl} -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [983]
    [984] 200 mg of 4-bromo-2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone was prepared in a manner similar to the synthesis in Example 32 using {(3 -N-acetylamino) benzene} boronic acid combined with 120 mg of 4-{(3-N-acetylamino) phenyl} -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl}- 120 mg of 3 ( 2H ) -furanone were obtained. mp: 56-57 o C. NMR: δ 0.95 (t, J = 7.2 Hz, 3H), 1.54 (s, 3H), 1.95 (m, 2H), 2.07 (s, 3H), 3.07 (s, 3H) , 6.92 (m, 1H), 7.33 (m, 1H), 7.56 (m, 2H), 7.85 (d, J = 8.7 Hz, 2H), 7.93 (d, J = 9.0 Hz, 2H), 8.00 (s, 1H). IR (cm −1 ): 3312, 3077, 2928, 2881, 1695, 1619, 1553, 1318, 1149, 958, 725, 641.
    [985] Example 34
    [986] 2-ethyl-2-methyl-4- {4- (1-N-methylpyrazolyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [987]
    [988] 210 mg of 2-ethyl-4-iodine-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone and {4- (1-N-methylpyrazolyl)}-trimethyl After 170 mg of lithium boronic acid salt was reacted, the reaction solution was stirred at 90 ° C. for 12 hours. The reaction solvent was removed by evaporation under reduced pressure, and the remaining residue was diluted with 50 mL of water. The aqueous layer was extracted with dichloromethane (30 mL x 3), and the organic layer was concentrated under reduced pressure. The remaining crude mixture was purified by column chromatography (hexane / ethyl acetate) to give solid 2-ethyl-2-methyl-4- {4- (1-N-methylpyrazolyl)}-5- {4- ( 100 mg of methylsulfonyl) phenyl} -3 ( 2H ) -furanone were obtained. mp: 78-80 o C. NMR: δ 0.92 (t, J = 7.5 Hz, 3H), 1.59 (s, 3H), 1.93 (m, 2H), 3.10 (s, 3H), 3.93 (s, 3H) , 7.38 (d, J = 0.6 Hz, 1H), 7.74 (br s, 1H), 8.03 (m, 4H).
    [989] Example 35
    [990] 4- (4-acetylphenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [991]
    [992] Step 1: 2-ethyl-4-iodine-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H) -Production of Furanone
    [993] 8.88 g of 2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone was dissolved in 50 ml of carbon tetrachloride and 50 ml of chloroform, followed by [bis (trifluoroacetase). Oxy) iodine] benzene (6.82 g) and iodine (4 g) were added. After stirring the reaction solution at room temperature for 4 hours, the reaction was stopped by addition of saturated aqueous sodium thiosulfate solution until the intrinsic color of iodine disappeared. The solution was extracted with 50 mL of water and dichloromethane (100 mL x 3). The organic layer was then concentrated under reduced pressure, and the remaining crude product was purified by column chromatography (hexane / ethyl acetate = 1: 1) to give 2-ethyl-4-iodine-2-methyl-5- {4- (methylsulfonyl 8.7 g)) phenyl} -3 ( 2H ) -furanone was obtained. NMR: δ 0.89 (t, J = 7.5 Hz, 3H), 1.51 (s, 3H), 1.93 (q, J = 7.5 Hz, 2H), 3.11 (s, 3H), 8.11 (d, J = 8.7 Hz, 2H), 8.34 (d, J = 8.7 Hz, 2H). IR (cm- 1 ): 2928, 1701, 1552, 1314, 1148, 747, 551.
    [994] Step 2: 4- (4-acetylphenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H) -Production of Furanone
    [995] 2-ethyl-4-iodine-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone (200 mg) was dissolved in 15 ml of toluene and 5 ml of ethanol and stirred To this was added 34 mg of tetrakis (triphenylphosphine) palladium (0), 5 ml of 2M aqueous sodium carbonate solution and 120 mg of 4-acetylbenzeneboronic acid. The reaction solution was stirred at 95 ° C. for 12 hours. The reaction solvent was removed by evaporation under reduced pressure, and the remaining residue was extracted with 50 mL of water and dichloromethane (30 mL x 3). The organic layer was concentrated under reduced pressure, and the remaining crude product was purified by column chromatography (hexane / ethyl acetate) to yield solid 4- (4-acetylphenyl) -2-ethyl-2-methyl-5- {4- (methyl 120 mg of sulfonyl) phenyl} -3 ( 2H ) -furanone were obtained. mp: 147-148 o C. NMR: δ 0.97 (t, J = 7.5 Hz, 3H), 1.56 (s, 3H), 1.99 (m, 2H), 2.62 (s, 3H), 3.08 (s, 3H) , 7.39 (d, J = 8.7 Hz, 2H), 7.83 (d, J = 8.7 Hz, 2H), 7.97 (m, 2H). IR (cm- 1 ): 2929, 1684, 1410, 1317, 1149, 1016, 769, 552.
    [996] Example 36
    [997] 2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- (3-pyridyl) -3 ( 2H ) -Furanone
    [998]
    [999] 4-bromo-2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone (200 mg) was dissolved in 15 ml of toluene and 5 ml of ethanol and stirred To the solution, 40 mg of tetrakis (triphenylphosphine) palladium (0), 5 ml of 2M aqueous sodium carbonate solution and 110 mg of (3-pyridyl) -trimethylboronic acid salt were added, and the reaction solution was added at 95 ° C. Stir for hours. The reaction solvent was removed by evaporation under reduced pressure, and the remaining residue was diluted with 50 mL of water. The aqueous solution was extracted with dichloromethane (30 mL x 3), and the organic layer was concentrated under reduced pressure. The remaining crude mixture was purified by column chromatography (hexane / ethyl acetate) to give 2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- (3-pyridyl) -3 ( 35 mg of 2H ) -furanone was obtained. NMR: δ 0.97 (t, J = 7.5 Hz, 3H), 1.57 (s, 3H), 2.00 (m, 2H), 3.09 (s, 3H), 7.37 (m, 1H), 7.71 (m, 1H), 7.83 (d, J = 9.0 Hz, 2H), 7.98 (d, J = 8.7 Hz, 2H), 8.46 (s, 1H), 8.58 (s, 1H). IR (cm −1 ): 3058, 2976, 1696, 1621, 1401, 1318, 1149, 926, 769, 726, 552.
    [1000] Example 37
    [1001] 4- (4- t -Butylphenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [1002]
    [1003] 150 mg of 2-ethyl-4-iodine-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone were prepared in a similar manner to the synthesis in step 2 of Example 35 ( 4- (4- t -butylphenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H combined with 117 mg of 4-t-butylbenzene) boronic acid 100 mg of) -furanone were obtained. mp: 45 ° C. NMR: δ 0.95 (t, J = 7.5 Hz, 3H), 1.33 (s, 9H), 1.54 (s, 3H), 1.96 (m, 2H), 3.08 (s, 3H), 7.18-7.21 (m, 2H ), 7.38-7.41 (m, 2H), 7.86-7.95 (m, 4H). IR (cm- 1 ): 2967, 2871, 1696, 1594, 1385, 1320, 1149, 769, 552.
    [1004] Example 38
    [1005] 4- (3-aminophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [1006]
    [1007] 200 mg of 2-ethyl-4-iodine-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone were prepared in a similar manner to the synthesis in step 2 of Example 35 ( Reaction with 110 mg of 3-aminobenzene) boronic acid to yield solid 4- (3-aminophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H )- 105 mg of furanone was obtained. mp: 77-78 o C. NMR: δ 0.94 (t, J = 7.5 Hz, 3H), 1.53 (s, 3H), 1.96 (m, 2H), 3.07 (s, 3H), 6.57 (m, 1H) , 6.66 (m, 2 H), 7.14 (m, 1 H), 7.91 (m, 4 H). IR (cm −1 ): 3457, 3370, 2926, 1692, 1620, 1403, 1317, 1148, 959, 854, 769, 552.
    [1008] Example 39
    [1009] 2-ethyl-4- {4- (fluoromethyl) phenyl} -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [1010]
    [1011] 200 mg of 2-ethyl-4-iodine-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone were added in a similar manner to the synthesis in step 2 of Example 35. Combined with 110 mg of 4- (fluoromethyl) benzene} boronic acid, 2-ethyl-4- {4- (fluoromethyl) phenyl} -2-methyl-5- {4- (methylsulfonyl) phenyl} 70 mg of -3 ( 2H ) -furanone was obtained. NMR: δ 0.96 (dt, J = 7.5, 2.1 Hz, 3H), 1.55 (s, 3H), 1.97 (m, 2H), 3.07 (s, 3H), 5.41 (d, J = 23.9 Hz, 2H), 7.37 (m, 4 H), 7.85 (m, 2 H), 7.93 (m, 2 H). IR (cm- 1 ): 2974, 2929, 1697, 1319, 1150, 769, 552.
    [1012] Example 40
    [1013] 4- {5- (2-acetylthienyl)}-2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [1014]
    [1015] 200 mg of 2-ethyl-4-iodine-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone, in a similar manner to the synthesis in step 2 of Example 35 Reaction with 100 mg of (2-acetylthiophene) -5-boronic acid to yield 4- {5- (2-acetylthienyl)}-2-ethyl-2-methyl-5- {4- (methylsulfonyl) 70 mg of phenyl} -3 ( 2H ) -furanone was obtained. NMR: δ 0.95 (t, J = 7.2 Hz, 3H), 1.56 (s, 3H), 1.95 (m, 2H), 2.55 (s, 3H), 3.13 (s, 3H), 7.21 (d, J = 4.2 Hz, 1H), 7.95 (d, J = 4.2 Hz, 1H), 7.85 (d, J = 8.1 Hz, 2H), 8.08 (d, J = 8.1 Hz, 2H). IR (cm <-1> ): 2926, 1690, 1315, 1150, 772, 552.
    [1016] Example 41
    [1017] 2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- {2- (3-methylthienyl)}-3 ( 2H ) -Furanone
    [1018]
    [1019] 2-ethyl-4-iodine-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 (2H200 mg of) -furanone was reacted with 100 mg of {2- (3-methylthiophene) -trimethyl lithium boron salt in a similar manner to the synthesis method in Example 36, 2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- {2- (3-methylthienyl)}-3 (2H150 mg of furanone were obtained. NMR: δ 0.95 (t,J= 7.5 Hz, 3H), 1.55 (s, 3H), 1.96 (s, 3H), 1.99 (m, 2H), 3.06 (s, 3H), 6.80 (d,J= 5.1 Hz, 1H), 7.36 (d,J= 5.1 Hz, 1H), 7.91 (m, 4H). IR (cm-One): 2974, 2926, 1701, 1618, 1318, 1149, 770, 729, 552.
    [1020] Example 42
    [1021] 2-ethyl-4- {3- (6-methoxypyridyl)}-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [1022]
    [1023] 150 mg of 2-ethyl-4-iodine-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone were prepared by {3- ( 6-methoxypyridine)} trimethylboronic acid salt combined with 98 mg of solid 2-ethyl-4- {3- (6-methoxypyridyl)}-2-methyl-5- {4- (methyl 100 mg of sulfonyl) phenyl} -3 ( 2H ) -furanone were obtained. mp: 61 o C. NMR: δ 0.95 (t, J = 7.5 Hz, 3H), 1.55 (s, 3H), 1.95 (m, 2H), 3.08 (s, 3H), 3.95 (s, 3H), 6.78 (d, J = 8.4 Hz, 1H), 7.53 (dd, J = 8.4, 2.4 Hz, 1H), 7.85-7.88 (m, 2H), 7.95-7.98 (m, 2H), 8.04 (d, J = 2.4 Hz, 1H). IR (cm −1 ): 2977, 2929, 1695, 1591, 1500, 1318, 1287, 1149, 1021, 769, 552.
    [1024] Example 43
    [1025] 5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-4-phenyl-3 ( 2H ) -Furanone
    [1026]
    [1027] Step 1: 2-ethyl-2-methyl-5- {4- (methylsulfinyl) phenyl} -3 ( 2H) -Production of Furanone
    [1028]
    [1029] 2-ethyl-2-methyl-5-{(4-methylthio) phenyl} -3 ( 2H ) -furanone (6.0 g) was dissolved in 50 ml of dichloromethane and stirred in a solution of 70% m -chloroper 5.9 g of oxybenzoic acid was dissolved in 100 mL of dichloromethane and added dropwise at 0 ° C. The reaction solution was stirred at 0 ° C. for 2 hours. After the solvent was removed under reduced pressure, the remaining residue was extracted with 100 mL of water and dichloromethane (50 mL × 2). The organic layer was concentrated under reduced pressure, and the remaining crude product was purified by column chromatography (hexane / ethyl acetate = 2: 1), and 2-ethyl-2-methyl-5- {4- (methylsulfinyl) phenyl} -3 4.5 g of ( 2H ) -furanone were obtained. NMR: δ 0.89 (t, J = 7.5 Hz, 3H), 1.48 (s, 3H), 1.91 (m, 2H), 2.78 (s, 3H), 6.13 (s, 1H), 8.07 (m, 4H).
    [1030] Step 2: 2-ethyl-4-iodine-2-methyl-5- {4- (methylsulfinyl) phenyl} -3 ( 2H) -Production of Furanone
    [1031]
    [1032] 8.2 g of 2-ethyl-2-methyl-5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone were dissolved in 200 ml of carbon tetrachloride and 200 ml of chloroform, followed by [bis (trifluoroacetic acid). Oxy) iodine] benzene (BTI) and 4.1 g of iodine. The mixture was stirred at room temperature for 6 hours and then the reaction was stopped by addition of saturated aqueous sodium thiosulfate solution until the intrinsic color of iodine disappeared. The reaction stopped solution was extracted with 300 mL of water and dichloromethane (200 mL x 3). The organic layer was concentrated under reduced pressure, and the residue was purified by column chromatography (hexane / ethylacetate = 1: 1) to give 2-ethyl-4-iodine-2-methyl-5- {4- (methylsulphi 10.0 g of nil) phenyl} -3 ( 2H ) -furanone were obtained. NMR: δ 0.89 (t, J = 7.5 Hz, 3H), 1.51 (s, 3H), 1.93 (m, 2H), 2.73 (s, 3H), 7.81 (d, J = 8.7 Hz, 2H), 8.38 ( d, J = 8.7 Hz, 2H).
    [1033] Step 3: 5- {4- (aminosulfonyl) phenyl} -2-ethyl-4-iodine-2-methyl-3 ( 2H) -Manufacture of furanone
    [1034]
    [1035] 8.0 g of 2-ethyl-4-iodine-2-methyl-5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone was added to 50 ml of anhydrous trifluoroacetic acid (TFAA) and 0 o C Stirred for 3 h. Next, the volatiles were removed under reduced pressure, and then treated with 30 ml of a mixed solution of triethylamine and methanol 1: 1. The solvent was removed under reduced pressure. The same process of methanol and triethylamine mixed solution treatment and solvent removal was repeated three times. The remaining residue was then dissolved in 100 mL of carbon tetrachloride at 0 ° C., then 5 mL of acetic acid saturated with chlorine was added dropwise. The reaction solution was stirred at 0 ° C. for 1 hour. Volatile material, including unreacted chlorine, was removed by evaporation under reduced pressure. The remaining residue was then mixed with 100 mL of THF and 20 mL of aqueous ammonia solution and the solution was stirred at room temperature for 2 hours. After the solvent was removed under reduced pressure, the remaining residue was extracted with an aqueous ammonium acetate solution and ethyl acetate. The ethyl acetate layer was concentrated under reduced pressure, and the resulting crude product was purified by column chromatography (hexane / ethyl acetate = 1: 1) to give 5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- 2.0 g of iodine-2-methyl-3 ( 2H ) -furanone were obtained. NMR: δ 0.90 (t, J = 7.5 Hz, 3H), 1.51 (s, 3H), 1.93 (m, 2H), 5.10 (br s, 2H), 8.08 (d, J = 8.7 Hz, 2H), 8.33 (d, J = 8.7 Hz, 2H).
    [1036] Step 4: 5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-4-phenyl-3 ( 2H) -Production of Furanone
    [1037] 100 mg of 5- {4- (aminosulfonyl) phenyl} -2-ethyl-4-iodine-2-methyl-3 ( 2H ) -furanone were added 90 mg of benzene boronic acid in a similar manner to step 2 of Example 35. And 30 mg of solid 5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-4-phenyl-3 ( 2H ) -furanone was obtained. mp: 153-154 o C. NMR: δ 0.95 (t, J = 7.5 Hz, 3H), 1.54 (s, 3H), 1.97 (m, 2H), 4.89 (br s, 2H), 7.26 (m, 2H ), 7.36 (m, 3H), 7.79 (d, J = 8.7 Hz, 2H), 7.90 (d, J = 8.7 Hz, 2H). IR (cm- 1 ): 3340, 3256, 1684, 1616, 1392, 1342, 1161.
    [1038] Example 44
    [1039] 5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-4- (3-thienyl) -3 ( 2H ) -Furanone
    [1040]
    [1041] 100 mg of 5- {4- (aminosulfonyl) phenyl} -2-ethyl-4-iodine-2-methyl-3 ( 2H ) -furanone were prepared in a similar manner to step 2 of Example 35 (3-thiophene 20 mg of solid 5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-4- (3-thienyl) -3 ( 2H ) -furanone by reaction with 70 mg of boronic acid Obtained. mp: 120-121 o C. NMR: δ 0.93 (t, J = 7.5 Hz, 3H), 1.52 (s, 3H), 1.95 (m, 2H), 5.08 (br s, 2H), 6.91 (dd, J = 5.1, 1.8 Hz, 1H), 7.31 (dd, J = 7.1, 3.0 Hz, 7.49 (dd, J = 3.0, 1.8 Hz, 1H), 7.86 (d, J = 8.7 Hz, 2H), 7.96 (d, J = 8.7 Hz, 2H) IR (cm -1 ): 3345, 3252, 1682, 1616, 1343, 1158. MS (FAB) 364 ( m + 1).
    [1042] Example 45
    [1043] 4- (4-acetylphenyl) -5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-3 ( 2H ) -Furanone
    [1044]
    [1045] 100 mg of 5- {4- (aminosulfonyl) phenyl} -2-ethyl-4-iodine-2-methyl-3 ( 2H ) -furanone were prepared in a similar manner to step 2 of Example 35 (4-acetylbenzene 15 mg of solid 4- (4-acetylphenyl) -5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-3 ( 2H ) -furanone by reaction with 70 mg of boronic acid Obtained. mp: 154-155 o C. NMR: δ 0.96 (t, J = 7.5 Hz, 3H), 1.56 (s, 3H), 1.98 (q, J = 7.5 Hz, 2H), 2.62 (s, 3H), 4.95 (br s, 2H), 7.39 (d, J = 8.7 Hz, 2H), 7.77 (d, J = 8.7 Hz, 2H), 7.93 (d, J = 8.7 Hz, 2H), 7.95 (d, J = 8.7 Hz, 2H). IR (cm −1 ): 3227, 1681, 1614, 1344, 1219, 1161. MS (FAB): 400 ( m + 1).
    [1046] Example 46
    [1047] 5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- (3-fluoro-4-methoxyphenyl) -2-methyl-3 ( 2H ) -Furanone
    [1048]
    [1049] 100 mg of 5- {4- (aminosulfonyl) phenyl} -2-ethyl-4-iodine-2-methyl-3 ( 2H ) -furanone were prepared in a manner similar to step 2 of Example 35 in a 3-fluoro- Reaction with 80 mg of 4-methoxybenzeneboronic acid to yield solid 5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- (3-fluoro-4-methoxyphenyl) -2-methyl- 25 mg of 3 ( 2H ) -furanone were obtained. mp: 113-114 o C. NMR: δ 0.94 (t, J = 7.5 Hz, 3H), 1.53 (s, 3H), 1.95 (q, J = 7.5 Hz, 2H), 3.91 (s, 3H), 4.96 (br s, 2H), 6.99 (m, 3H), 7.80 (d, J = 8.4 Hz, 2H), 7.93 (d, J = 8.7 Hz, 2H). IR (cm- 1 ): 3259, 1689, 1608, 1517, 1270, 1159. MS (FAB): 406 ( m + 1).
    [1050] Example 47
    [1051] 2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -4-phenyl-3 ( 2H ) -Furanone
    [1052]
    [1053] Step 1: Preparation of 4-ethyl-1- {4- (methylthio) phenyl} -2-hexine-1,4-diol
    [1054]
    [1055] 3-ethyl-1-pentin-3-ol (7.7 mL) was dissolved in 300 mL of anhydrous THF, and 100 mL of 1.4 M methyllithium in hexane was added dropwise to -78 o C under an argon atmosphere. The mixture was further stirred for 30 minutes, then 4- (methylthio) benzaldehyde (9.3 mL) was slowly added dropwise. The reaction mixture was further stirred at room temperature for 12 hours while the cooling bath was removed and the reaction temperature was slowly raised to room temperature. Next, diluted hydrochloric acid aqueous solution was added to stop the reaction. After the solvent was removed under reduced pressure, the remaining residue was extracted with brine and dichloromethane (150 mL x 3). The organic layer was concentrated under reduced pressure, and the remaining crude product was purified by recrystallization with hexane and ethyl acetate (4: 1) to give a low melting solid 4-ethyl-1- {4- (methylthio) phenyl} -2-hexyne-. 11.8 g of 1,4-diol were obtained. mp: 64-65 o C. NMR: δ 1.04 (t, J = 7.5 Hz, 6H), 1.70 (q, J = 7.5 Hz, 4H), 2.49 (s, 3H), 5.47 (s, 1H), 7.26 (d, J = 8.4 Hz, 2H), 7.45 (d, J = 8.4 Hz, 2H). IR (cm- 1 ): 3368, 2970, 2207, 1637, 1589, 1262, 1093.
    [1056] Step 2: Preparation of 4-ethyl-4-hydroxy-1- {4- (methylthio) phenyl} -2-hexyn-1-one
    [1057]
    [1058] Silate (20 g) and 4-ethyl-1- {4- (methylthio) phenyl} -2-hexine-1,4-diol (11 g) were suspended in 300 ml of dichloromethane and stirred, followed by pyridinium 2.5 g of dichromate (PDC) was added dropwise at 0 ° C. The reaction mixture was stirred at room temperature for 12 hours. Insoluble and metallic material was removed by filtration with Florisil. The filtrate was extracted with dilute aqueous hydrochloric acid solution and dichloromethane (150 mL x 3). The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure, and the remaining crude product was recrystallized from a mixed solution of hexane and ethyl acetate 5: 1 to give solid 4-ethyl-4-hydroxy-1- {4- (methylthio) phenyl} -2 having a low melting point. 7.8 g of hexyn-1-one were obtained. mp: 49-50 o C. NMR: δ 1.12 (t, J = 7.5 Hz, 6H), 1.83 (q, J = 7.5 Hz, 4H), 2.15 (br s, 1H), 2.54 (s, 3H), 7.28 (d, J = 8.7 Hz, 2H), 8.02 (d, J = 8.7 Hz, 2H). IR (cm -1 ): 3432, 2970, 2208, 1636, 1588, 1285, 1095.
    [1059] Step 3: 2,2-diethyl-5- {4- (methylthio) phenyl} -3 ( 2H) -Production of Furanone
    [1060]
    [1061] 10 g of 4-ethyl-4-hydroxy-1- {4- (methylthio) phenyl} -2-hexyn-1-one are dissolved in 300 ml of methanol, and 4 ml of diethylamine is added thereto at room temperature for 12 hours. Stirred. The solvent was then removed under reduced pressure, and the remaining residue was extracted with dilute hydrochloric acid solution and dichloromethane (50 mL x 3). The organic layer was washed with brine, and then concentrated under reduced pressure to obtain 5.6 g of 2,2-diethyl-5- {4- (methylthio) phenyl} -3 ( 2H ) -furanone. The crude product was used in the next step without further purification. NMR: δ 0.85 (t, J = 7.5 Hz, 6H), 1.88 (q, J = 7.5 Hz, 4H), 2.54 (s, 3H), 5.96 (s, 1H), 7.31 (d, J = 9.0 Hz, 2H), 7.75 (d, J = 9.0 Hz, 2H). IR (cm -1 ): 2971, 1690, 1597, 1487, 1408, 1364, 1162, 1095.
    [1062] Step 4: 2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H) -Production of Furanone
    [1063]
    [1064] The crude product 2,2-diethyl-5- {4- (methylthio) phenyl} -3 ( 2H ) -furanone (5.6 g) obtained in the previous step was dissolved in 50 ml of THF and 50 ml of methanol and stirred. To the solution, 20 g of oxone was dissolved in 50 ml of water and added dropwise at 0 ° C. The mixture was then stirred at rt for 14 h. Insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The remaining residue was extracted with water and ethyl acetate (150 mL x 2). The ethyl acetate layer was concentrated, and the remaining crude product was purified by column chromatography (hexane / ethyl acetate = 2: 1) to give solid 2,2-diethyl-5- {4- (methylsulfonyl) phenyl}- 4.5 g of 3 ( 2H ) -furanone was obtained. mp: 109-110 o C. NMR: 0.86 (t, J = 7.5 Hz, 6H), 1.91 (q, J = 7.5 Hz, 4H), 3.10 (s, 3H), 6.14 (s, 1H), 8.04 ( d, J = 9.0 Hz, 2H), 8.09 (d, J = 9.0 Hz, 2H). IR (cm- 1 ): 2973, 1695, 1588, 1561, 1408, 1315, 1152.
    [1065] Step 5: 4-bromo-2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H) -Production of Furanone
    [1066]
    [1067] 1.5 ml of bromine in a solution obtained by dissolving 2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone (4.5 g) in 200 ml of chloroform and 3 ml of acetic acid. Was added dropwise at 0 o C. The temperature of the solution was raised to room temperature and further stirred for 4 hours. The reaction was stopped by addition of saturated aqueous sodium thiosulfate solution until the intrinsic color of bromine disappeared. The reaction mixture was extracted with dichloromethane (100 mL x 2), and then the organic layer was dried over anhydrous magnesium sulfate. After magnesium sulfate was filtered off, the filtrate was concentrated under reduced pressure. The remaining crude product was purified by recrystallization with hexane and ethyl acetate to give 4.5 g of 4-bromo-2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone. It was. mp: 130-131 o C. NMR: δ 0.88 (t, J = 7.5 Hz, 6H), 1.95 (q, J = 7.5 Hz, 4H), 3.11 (s, 3H), 8.12 (d, J = 8.7 Hz , 2H), 8.42 (d, J = 8.7 Hz, 2H). IR (cm −1 ): 2973, 1705, 1583, 1558, 1315, 1160, 1084.
    [1068] Step 6: 2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -4-phenyl-3 ( 2H) -Production of Furanone
    [1069] 4-Bromo-2,2-diethyl-2-5- {4- (methylsulfonyl) phenyl} -3 (2H ) -furanone (300 mg) was dissolved in 25 ml of toluene and 10 ml of ethanol and stirred To one solution was added 40 mg of tetrakis (triphenylphosphine) palladium (0), 10 ml of 2M aqueous sodium carbonate solution and 140 mg of benzeneboronic acid. The reaction solution was stirred at 95 ° C. for 12 hours. The reaction solvent was removed by evaporation under reduced pressure, and the remaining residue was extracted with 50 mL of water and dichloromethane (30 mL x 3). The organic layer was concentrated under reduced pressure, and the remaining crude mixture was purified by column chromatography (hexane / ethyl acetate) to obtain solid 2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -4-phenyl. 130 mg of -3 ( 2H ) -furanone was obtained. mp: 139-140 o C. NMR: δ 0.93 (t, J = 7.5 Hz, 6H), 1.99 (q, J = 7.5 Hz, 4H), 3.07 (s, 3H), 7.24 (m, 2H), 7.37 (m, 3H), 7.86 (d, J = 8.7 Hz, 2H), 7.93 (d, J = 8.7 Hz, 2H). IR (cm- 1 ): 2972, 1695, 1621, 1403, 1318, 1149.
    [1070] Example 48
    [1071] 4- (3-chlorophenyl) -2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [1072]
    [1073] 300 mg of 4-bromo-2,2-diethyl-2-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone was prepared in a similar manner to the synthesis in step 6 of Example 47 Reacted with 160 mg of (3-chlorobenzene) boronic acid to give 4- (3-chlorophenyl) -2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) as a solid. -160 mg of furanone was obtained. mp: 131-132 o C. NMR: δ 0.93 (t, J = 7.5 Hz, 6H), 1.98 (q, J = 7.5 Hz, 4H), 3.08 (s, 3H), 7.12 (m, 1H), 7.30 (m, 3H), 7.85 (d, J = 8.4 Hz, 2H), 7.95 (d, J = 8.4 Hz, 2H). IR (cm -1 ): 2973, 1695, 1620, 1403, 1318, 1150.
    [1074] Example 49
    [1075] 4- (4-acetylphenyl) -2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [1076]
    [1077] 300 mg of 4-bromo-2,2-diethyl-2-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone were prepared in a similar manner to step 6 of Example 47 (4- Combined with 160 mg of acetylbenzene) boronic acid to form a foamy substance 4- (4-acetylphenyl) -2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone 80 mg was obtained. NMR: δ 0.94 (t, J = 7.5 Hz, 6H), 2.00 (q, J = 7.5 Hz, 4H), 2.62 (s, 3H), 3.11 (s, 3H), 7.39 (d, J = 8.4 Hz, 2H), 7.86 (d, J = 8.4 Hz, 2H), 7.97 (dd, J = 8.4, 1.5 Hz, 4H). IR (cm- 1 ): 2973, 1693, 1617, 1410, 1317, 1151.
    [1078] Example 50
    [1079] 2,2-diethyl-4- (3-fluoro-4-methoxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [1080]
    [1081] 300 mg of 4-bromo-2,2-diethyl-2-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone was prepared in a similar manner to the synthesis in step 6 of Example 47 To 180 mg of (3-fluoro-4-methoxybenzene) boronic acid to give solid 2,2-diethyl-4- (3-fluoro-4-methoxyphenyl) -5- {4- 100 mg of (methylsulfonyl) -phenyl} -3 ( 2H ) -furanone were obtained. mp: 183-184 o C. NMR: δ 0.92 (t, J = 7.5 Hz, 6H), 1.97 (q, J = 7.5 Hz, 4H), 3.09 (s, 3H), 3.92 (s, 3H), 6.99 (m, 3H), 7.87 (d, J = 8.7 Hz, 2H), 7.96 (d, J = 9.0 Hz, 2H). IR (cm- 1 ): 2972, 1694, 1518, 1317, 1149.
    [1082] Example 51
    [1083] 2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -4- (3-thienyl) -3 ( 2H ) -Furanone
    [1084]
    [1085] 300 mg of 4-bromo-2,2-diethyl-2-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone was treated with thiophene- in a similar manner to step 6 of Example 47. Combined with 130 mg of 3-boronic acid to form a foamy substance 2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -4- (3-thienyl) -3 ( 2H ) -furanone 80 mg was obtained. NMR: δ 0.94 (t, J = 7.5 Hz, 6H), 1.98 (q, J = 7.5 Hz, 4H), 3.10 (s, 3H), 6.91 (dd, J = 5.4, 1.5 Hz, 1H), 7.33 ( dd, J = 5.1, 3.0 Hz, 1H), 7.50 (dd, J = 3.0, 1.2 Hz, 1H), 7.93 (d, J = 8.7 Hz, 2H), 8.00 (d, J = 8.7 Hz, 2H). IR (cm- 1 ): 2971, 1693, 1311, 1149.
    [1086] Example 52
    [1087] 2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -4- (3-pyridyl) -3 ( 2H ) -Furanone
    [1088]
    [1089] 4-Bromo-2,2-diethyl-2-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone (300 mg) was dissolved in 25 ml of toluene and 10 ml of ethanol. To the stirred solution was added 40 mg of tetrakis (triphenylphosphine) palladium (0), 10 mL of 2M aqueous sodium carbonate solution and 130 mg of (3-pyridyl) -trimethylboronic acid salt. The reaction solution was stirred at 95 ° C. for 12 hours. The reaction solvent was removed by evaporation under reduced pressure and the remaining residue was extracted with 50 mL of water and dichloromethane (30 mL x 3). The organic layer was concentrated under reduced pressure. The resulting crude mixture was purified by column chromatography (hexane / ethyl acetate) to give foamy material 2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -4- (3-pyridyl 30 mg of) -3 ( 2H ) -furanone was obtained. NMR: δ 0.94 (t, J = 7.5 Hz, 6H), 2.00 (q, J = 7.5 Hz, 4H), 3.09 (s, 3H), 7.36 (m, 1H), 7.54 (m, 1H), 7.84 ( d, J = 9.0 Hz, 2H), 7.98 (d, J = 8.7 Hz, 2H), 8.44 (d, J = 1.8 Hz, 1H), 8.58 (dd, J = 4.8, 1.8 Hz, 1H). IR (cm- 1 ): 2972, 1695, 1621, 1400, 1316, 1239, 1140.
    [1090] Example 53
    [1091] 2-{(4-methylsulfonyl) phenyl} -3-phenyl-1-oxa-spiro [4,4] non-2-en-4-one
    [1092]
    [1093] Step 1: Preparation of 1- [3-hydroxy-3- (4-methylthiophenyl) -prop-1-ynyl] -cyclopentanol
    [1094]
    [1095] In a solution of 1-ethynyl-cyclopentan-1-ol (2.0 g) dissolved in 15 ml of anhydrous THF under -78 ° C. and argon atmosphere, 18 ml of 2.5M butyllithium in hexane was added for 20 minutes. It was added dropwise over. The reaction solution was further stirred for 20 minutes and then 4-methylthiobenzaldehyde (2.7 g) was added dropwise. After further stirring for 2 hours, the reaction was stopped by adding 20 ml of diluted aqueous hydrochloric acid solution. After the reaction solvent was removed under reduced pressure, the remaining aqueous solution was extracted with dichloromethane (30 mL x 3). The organic layer was concentrated under reduced pressure, and the remaining residue was purified by column chromatography (hexane / ethyl acetate = 1: 1) to obtain solid 1- [3-hydroxy-3- {4- (methylthio) phenyl} -prop-. 3.48 g of 1-ynyl] -cyclopentanol were obtained. mp: 118-120 o C. NMR: δ 0.73 (m, 4H), 1.87 (m, 4H), 2.16 (s, 1H), 2.48 (s, 3H), 2.55 (s, 1H), 5.43 (d, J = 5.7 Hz, 1H), 7.24 (d, J = 8.4 Hz, 2H), 7.42 (d, J = 8.4 Hz, 2H).
    [1096] Step 2: Preparation of 3- (1-hydroxy-cyclopentyl) -1- {4- (methylthio) phenyl} -propynone
    [1097]
    [1098] 1.54 g of 1- [3-hydroxy-3- {4- (methylthio) phenyl} -prop-1-ynyl] -cyclopentanol was dissolved in 20 ml of dichloromethane, followed by 3.32 g of pyridinium dichromate and 3 g of celite was added. The suspension was stirred overnight at room temperature and then the insoluble material was removed by filtration with Florisil. The filtrate was column chromatography (hexane / ethyl acetate) to obtain 1.0 g of 3- (1-hydroxy-cyclopentyl) -1- {4- (methylthio) phenyl} -propynone. NMR: δ 1.85 (m, 4H), 2.12 (m, 4H), 2.53 (s, 3H), 5.95 (s, 1H), 7.27 (m, 2H), 8.01 (m, 2H).
    [1099] Step 3: Preparation of 2- {4- (methylthio) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one
    [1100]
    [1101] 1.54 g of 3- (1-hydroxy-cyclopentyl) -1- {4- (methylthio) phenyl} -propynone was dissolved in 50 ml of ethanol, and 0.75 ml of diethylamine diluted with 50 ml of ethanol was added dropwise. . After the reaction solution was stirred at room temperature for 4 hours, the solvent was removed under reduced pressure. The remaining residue was extracted with 20 mL of water and dichloromethane (30 mL x 3). The organic layer was concentrated and separated by column chromatography (hexane / ethyl acetate) to give 2- {4- (methylthio) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one. 858 mg was obtained. NMR: δ1.89 (m, 6H), 1.92 (m, 2H), 2.47 (s, 3H), 5.89 (s, 1H), 7.24 (d, J = 8.4 Hz, 2H), 7.42 (d, J = 8.7 Hz, 2H).
    [1102] Step 4: Preparation of 3-bromo-2- {4- (methylthio) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one
    [1103]
    [1104] After dissolving 147 mg of 2- {4- (methylthio) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one in 30 ml of carbon tetrachloride, 1 ml of bromine and 0.1 ml of acetic acid were added. Added. The reaction mixture was stirred at room temperature for 1 hour. Then, the reaction was stopped by adding a saturated aqueous sodium thiosulfate solution until the intrinsic color of bromine disappeared. The solution was stopped and extracted with dichloromethane (10 mL x 3). The organic layer was concentrated under reduced pressure, and the residue was purified by column chromatography (hexane / ethyl acetate) to give 3-bromo-2- {4- (methylthio) phenyl} -1-oxa-spiro [4,4 ] 50 mg of non-2-en-4-one were obtained. NMR: δ 1.98 (m, 4H), 2.11 (m, 4H), 2.55 (s, 3H), 7.32 (d, J = 8.7 Hz, 2H), 8.13 (d, J = 8.7 Hz, 2H).
    [1105] Step 5: Preparation of 3-bromo-2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one
    [1106]
    [1107] 50 mg of 3-bromo-2- {4- (methylthio) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one in 5 ml of ethanol, 5 ml of THF and 5 ml of water Stirred overnight at room temperature with 292 mg of oxone. Insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The remaining aqueous layer was extracted with dichloromethane, and the organic layer was concentrated under reduced pressure. The remaining residue was purified by column chromatography (hexane / ethyl acetate) to give solid 3-bromo-2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,4] non-2. 68 mg of -en-4-one was obtained. mp: 127-128 o C. NMR: δ 1.98 (m, 6H), 2.12 (m, 2H), 3.11 (s, 3H), 8.09 (d, J = 8.7 Hz, 2H), 8.37 (d, J = 8.7 Hz, 2H).
    [1108] Step 6: Preparation of 2- {4- (methylsulfonyl) phenyl} -3-phenyl-1-oxa-spiro [4,4] non-2-en-4-one
    [1109] 3-bromo-2- (4- (methylsulfonyl) phenyl) -1-oxa-spiro [4,4] non-2-en-4-one (77 mg) was added to 5 ml of toluene and 15 ml of ethanol. 15 mg of tetrakis (triphenylphosphine) palladium (0), 5 ml of 2M aqueous sodium carbonate solution and 27 mg of benzeneboronic acid were added to the dissolved and stirred solution. Next, the reaction solution was stirred at 90 ° C. for 12 hours. The reaction solvent was removed by evaporation under reduced pressure, and the remaining residue was extracted with 20 mL of water and dichloromethane (30 mL × 1). The organic layer was concentrated under reduced pressure, and the remaining crude mixture was purified by column chromatography (hexane / ethyl acetate) to yield solid 2- {4- (methylsulfonyl) phenyl} -3-phenyl-1-oxa-spiro [4. , 4] non-2-en-4-one 57 mg was obtained. mp: 184-185 o C. NMR: δ 2.09 (m, 6H), 2.17 (m, 2H), 3.06 (s, 3H), 7.26 (m, 2H), 7.35 (m, 3H), 7.81 (d, J = 8.1 Hz, 2H), 7.92 (d, J = 8.1 Hz, 2H). IR (cm- 1 ): 2925, 1695, 1591, 1403, 1150, 771.
    [1110] Example 54
    [1111] 3- (4-isopropylphenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one
    [1112]
    [1113] 3-bromo-2- (4-methylsulfonylphenyl) -1-oxa-spiro [4,4] non-2-en-4-one (105 mg) was dissolved in 5 ml of toluene and 15 ml of ethanol. To the stirred solution, 20 mg of tetrakis (triphenylphosphine) palladium (0), 5 ml of 2M aqueous sodium carbonate solution and 50 mg of 4-isopropylbenzeneboronic acid were added. The reaction solution was then stirred at 90 ° C. for 12 hours. The solvent was removed under reduced pressure, and the remaining residue was extracted with 20 mL of water and dichloromethane (30 mL x 3). The organic layer was concentrated under reduced pressure, and the remaining crude product was purified by column chromatography (hexane / ethyl acetate) to obtain solid 3- (4-isopropylphenyl) -2- {4- (methylsulfonyl) phenyl} -1. 87 mg of oxa-spiro [4,4] non-2-en-4-one was obtained. mp: 139-140 o C. NMR: δ 1.25 (s, 3H), 1.27 (s, 3H), 2.04 (m, 6H), 2.15 (m, 2H), 2.92 (m, 1H), 3.06 (s, 3H), 7.21 (m, 4H), 7.83 (d, J = 8.7 Hz, 2H), 7.93 (d, J = 8.7 Hz, 2H). IR (cm- 1 ): 2960, 1694, 1622, 1386, 1318, 1161, 768.
    [1114] Example 55
    [1115] 3- (4-acetylphenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one
    [1116]
    [1117] 110 mg of 3-bromo-2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one similar to the synthesis method in Example 54 Combined with 55 mg of (4-acetylbenzene) boronic acid to form solid 3- (4-acetylphenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,4] non 93 mg of 2-en-4-one were obtained. mp: 126-130 o C. NMR: δ 2.04 (m, 6H), 2.17 (m, 2H), 2.61 (s, 3H), 3.08 (s, 3H), 7.39 (d, J = 8.4 Hz, 2H) , 7.81 (d, J = 8.4 Hz, 2H), 7.94 (m, 4H). IR (cm- 1 ): 2963, 1689, 1317, 1150, 771.
    [1118] Example 56
    [1119] 2- {4- (methylsulfonyl) phenyl} -3-phenyl-1-oxa-spiro [4,5] dec-2-en-4-one
    [1120]
    [1121] Step 1: Preparation of 1- [3-hydroxy-3- (methylthiophenyl) -prop-1-ynyl] -cyclohexan-1-ol
    [1122]
    [1123] In a solution of 1-ethynyl-cyclohexane-1-ol (3.2 g) dissolved in anhydrous THF 80 ml under an argon atmosphere at -78 ° C, 35 ml of 2.5M butyllithium in hexane was stirred for 10 minutes. Added dropwise. The reaction solution was further stirred for 20 minutes, and then 4-methylthiobenzaldehyde (3.2 mL) was added dropwise. After further stirring for 2 hours, dilute hydrochloric acid solution was added to stop the reaction. The reaction solvent was removed under reduced pressure, and the remaining aqueous solution was extracted with dichloromethane. The organic layer was concentrated under reduced pressure, and the remaining residue was purified by column chromatography (hexane / ethyl acetate) to give 1- [3-hydroxy- {4- (methylthio) phenyl} -prop-1-ynyl] -cyclo 4.67 g of hexanol were obtained. NMR: δ 1.45 (m, 6H), 1.70 (m, 2H), 1.90 (m, 2H), 2.17 (d, 1H), 2.49 (s, 3H), 3.57 (s, 1H), 5.48 (d, J = 6.0 Hz 1H), 7.26 (d, J = 8.4 Hz, 2H), 7.46 (d, J = 8.4 Hz, 2H). IR (cm- 1 ): 3343, 2934, 1445, 1091.
    [1124] Step 2: Preparation of 3- (1-hydroxycyclohexyl) -1- {4- (methylthio) phenyl} propinone
    [1125]
    [1126] 3.56 g of 1- [3-hydroxy- {4- (methylthio) phenyl-prop-1-ynyl] -cyclohexanol was dissolved in 60 ml of dichloromethane, followed by addition of 1.79 g of chromium oxide. The reaction mixture was stirred overnight at room temperature, after which the insoluble material was removed by filtration with Florisil. The filtrate was concentrated under reduced pressure, and the remaining residue was purified by column chromatography (hexane / ethyl acetate) to give 3- (1-hydroxycyclohexyl) -1- {4- (methylthio) phenyl} -propynone. 1.42 g were obtained. NMR: δ 1.56 (m, 4H), 1.76 (m, 4H), 2.03 (m, 2H), 2.33 (s, 1H), 2.53 (s, 3H), 7.26 (d, J = 8.7 Hz, 2H), 8.01 (d, J = 8.7 Hz, 2H). IR (cm- 1 ): 3416, 2936, 1637, 1588, 1263, 1096.
    [1127] Step 3: Preparation of 2- {4- (methylthio) phenyl} -1-oxa-spiro [4,5] dec-2-en-4-one
    [1128]
    [1129] 1.3 g of 3- (1-hydroxycyclohexyl) -1- {4- (methylthio) phenyl} -propynone was reacted with 0.6 ml of diethylamine in a similar manner to step 3 of Example 53, whereby 2- 858 mg of {4- (methylthio) phenyl} -1-oxa-spiro [4,5] dec-2-en-4-one were obtained. NMR: δ 1.62-1.82 (m, 10H), 2.54 (s, 3H), 5.92 (s, 1H), 7.30 (d, J = 8.1 Hz, 2H), 7.75 (d, J = 8.4 Hz, 2H). IR (cm −1 ): 2933, 1686, 1588, 1408, 1095, 744.
    [1130] Step 4: Preparation of 2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,5] dec-2-en-4-one
    [1131]
    [1132] 486 mg of 2- {4- (methylthio) phenyl} -1-oxa-spiro [4,5] dec-2-en-4-one was reacted with 1 g of oxone in a similar manner to step 4 of Example 53 470 mg of 2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,5] dec-2-en-4-one were obtained. NMR: δ 1.77 (m, 10H), 3.09 (s, 3H), 6.10 (s, 1H), 8.05 (m, 4H). IR (cm- 1 ): 2935, 1694, 1589, 1408, 1315, 1153, 775.
    [1133] Step 5: Preparation of 3-bromo-2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,5] dec-2-en-4-one
    [1134]
    [1135] 50 mg of 2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,5] dec-2-en-4-one in a similar manner to step 5 of Example 53, with 0.1 ml of acetic acid Reaction with bromine (0.5 mL) at the bottom gives 68 mg of 3-bromo-2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,5] dec-2-en-4-one Obtained. mp: 163-164 o C NMR: δ 1.79 (m, 10H), 3.11 (s, 3H), 8.10 (d, J = 8.1 Hz, 2H), 8.40 (d, J = 8.1 Hz, 2H). IR (cm- 1 ): 2936, 1709, 1583, 1316, 1149, 912, 744.
    [1136] Step 6: Preparation of 2- {4- (methylsulfonyl) phenyl} -3-phenyl-1-oxa-spiro [4,5] dec-2-en-4-one
    [1137] 102 mg of 3-bromo-2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,5] dec-2-en-4-one was dissolved in 3 ml of toluene and 15 ml of ethanol. Then, 16 mg of tetrakis (triphenylphosphine) palladium (0), 3 ml of a 2M sodium carbonate aqueous solution and 35 mg of benzeneboronic acid were added. The reaction mixture was stirred at 90 ° C. for 12 hours and purified in a similar manner to step 6 of Example 53 to give solid 2- {4- (methylsulfonyl) phenyl} -3-phenyl-1-oxa-spiro 50 mg of [4,5] dec-2-en-4-one were obtained. mp: 126-127 o C. NMR: δ 1.77-1.85 (m, 10H), 3.06 (s, 3H), 7.27 (m, 2H), 7.35 (m, 3H), 7.83 (d, J = 8.1 Hz, 2H), 7.94 (d, J = 8.1 Hz, 2H). IR (cm −1 ): 2936, 1693, 1621, 1404, 1318, 1147, 1129, 730.
    [1138] Example 57
    [1139] 3- (4-acetylphenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,5] dec-2-en-4-one
    [1140]
    [1141] 84 mg of 3-bromo-2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,5] dec-2-en-4-one was dissolved in 3 ml of toluene and 15 ml of ethanol. Then 15 mg of tetrakis (triphenylphosphine) palladium (0), 3 ml of 2M aqueous sodium carbonate solution and 40 mg of (4-acetylbenzene) boronic acid were added. The reaction mixture was stirred at 90 ° C. for 12 hours. The reaction mixture was purified in a similar manner to step 6 of Example 56, whereby 3- (4-acetylphenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,5] dec- 35 mg of 2-en-4-one were obtained. NMR: δ 1.78-1.86 (m, 10H), 2.61 (s, 3H), 3.08 (s, 3H), 7.37 (d, J = 8.4 Hz, 2H), 7.84 (d, J = 8.4 Hz, 2H), 7.97 (m, 4 H). IR (cm- 1 ): 2963, 1689, 1621, 1317, 1150, 771.
    [1142] The compounds of Examples 58-103 were synthesized in a similar manner to the synthesis of Example 2.
    [1143] [Example 58] to [Example 103]
    [1144]
    [1145]
    [1146]
    [1147]
    [1148]
    [1149]
    [1150] Example 104
    [1151] 2,2-dimethyl-4- (4-hydroxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [1152]
    [1153] 30 mg of 2,2-dimethyl-4- (4-methoxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone (Example 3) was dissolved in 30 ml of dichloromethane. And 0.1 ml of boron tribromide salt (1.0 M solution in CH 2 Cl 2 ) was stirred at room temperature for 4 hours. Next, 10 ml of sodium thiosulfate aqueous solution was added to the reaction mixture. The reaction solution was concentrated under reduced pressure, and extracted with 50 mL of water and dichloromethane (50 mL x 3). The organic layer was concentrated under reduced pressure and purified by column chromatography (ethyl acetate) to give 2,2-dimethyl-4- (4-hydroxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 (2H 25 mg of furanone were obtained. mp: 150-152 o C. NMR: δ 1.56 (s, 6H), 2.77 (s, 1H), 3.07 (s, 3H), 6.81 (d, J = 8.7 Hz, 2H), 7.14 (d, J = 8.7 Hz, 2H), 7.90 (m, 4H). IR (cm <-1> ): 3492, 2929, 1696, 1597, 1393, 1151, 914, 744.
    [1154] The compounds of Examples 105 and 107 were prepared from the corresponding methoxy compounds in a similar manner to the synthesis of Example 104.
    [1155] [Example 105] to [Example 107]
    [1156]
    [1157]
    [1158] Example 108
    [1159] 4- {3- (acetylamino) phenyl} -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [1160]
    [1161] 20 mg of 4- (3-aminophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone (Example 66) were dissolved in 10 ml of anhydrous dichloromethane. 0.3 ml of acetic anhydride was added at 0 ° C. and stirred at room temperature for 1 hour. The reaction mixture was then concentrated under reduced pressure and extracted with water and dichloromethane. The organic layer was concentrated under reduced pressure and purified by column chromatography (hexane / ethyl acetate = 2: 1) to obtain 4- {3-N- (acetylamino) phenyl} -2,2-dimethyl-5- {4- (methylsulfur 15 mg of phonyl) phenyl} -3 ( 2H ) -furanone were obtained. mp: 217-218 ° C. NMR: δ 1.55 (s, 6H), 2.11 (s, 3H), 3.05 (s, 3H), 6.96 (d, J = 7.5 Hz, 1H), 7.31 (d, J = 8.1 Hz, 1H), 7.40 ( s, 1H), 7.49 (d, J = 8.1 Hz), 7.84 (d, J = 8.4 Hz, 2H), 7.91 (d, J = 8.4 Hz, 2H). IR (cm −1 ): 3341, 1690, 1424, 1316, 1149, 959, 770.
    [1162] Example 109
    [1163] 2,2-dimethyl-4,5-di {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [1164]
    [1165] 50 mg of 2,2, -dimethyl-5- {4- (methylsulfonyl) phenyl} -4- {4- (methylthio) phenyl} -3 ( 2H ) -furanone (Example 72) was added to dichloromethane 10 Was dissolved in 2 ml of methanol and stirred with 300 mg of oxone at room temperature for 4 hours. Undissolved material was removed by filtration and the filtrate was washed with aqueous sodium bicarbonate solution. The organic layer was concentrated under reduced pressure, and then purified by column chromatography (ethyl acetate) to give 2,2-dimethyl-4,5-di {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone 45 Mg was obtained. mp: 245-257 degreeC. NMR: δ 1.60 (s, 6H), 3.08 (s, 3H), 3.10 (s, 3H), 7.50-7.53 (m, 2H), 7.79-7.82 (m, 2H), 7.94-8.00 (m, 4H) . IR (cm −1 ): 2931, 1698, 1510, 1387, 1258, 1150, 960, 846, 770.
    [1166] Example 110
    [1167] 2,2-dimethyl-4- {4- (ethylsulfonyl) phenyl} -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [1168]
    [1169] 100 mg of 2,2-dimethyl-4- {4- (ethylthio) phenyl} -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone (Example 88) 10 ml of dichloromethane And dissolved in 2 ml of methanol and stirred with 400 mg of oxone for 12 hours at room temperature. Undissolved material was removed by filtration and the filtrate was washed with aqueous sodium bicarbonate solution. The organic layer was concentrated under reduced pressure and purified by column chromatography (ethyl acetate) to give 2,2-dimethyl-4- {4- (ethylsulfonyl) phenyl} -5- {4- (methylsulfonyl) phenyl} -3 ( 70 mg of 2H ) -furanone was obtained. mp: 198-203 degreeC. NMR: δ 1.29-1.34 (t, J = 7.2 Hz, 3H), 1.60 (s, 6H), 3.10 (s, 3H), 3.10-3.18 (q, J = 7.5 Hz, 2H), 7.49-7.52 ( m, 2H), 7.79-7.82 (m, 2H), 7.90-7.93 (m, 2H), 7.97-7.99 (m, 2H). IR (cm −1 ): 1697, 1619, 1384, 1315, 1150, 960, 770.
    [1170] Example 111
    [1171] 2,2-dimethyl-4- {4- (1-hydroxyethyl) phenyl} -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [1172]
    [1173] 4- (4-acetylphenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone (150 mg, Example 10) in 40 ml of methanol, sodium boro A mixture of hydride (35 mg) and cerium (III) chloride (20 mg) was stirred at room temperature for 12 hours before water was added. After methanol was removed under reduced pressure, and the remaining aqueous solution was extracted with ethyl acetate. The ethyl acetate layer was concentrated under reduced pressure and purified by column chromatography (hexane / ethyl acetate = 1: 1) to give 2,2-dimethyl-4- {4- (1-hydroxyethyl) phenyl} -5- {4- 100 mg of (methylsulfonyl) phenyl} -3 ( 2H ) -furanone were obtained. NMR: δ 1.51-1.53 (d, J = 6.3 Hz, 3H), 1.58 (s, 6H), 3.07 (s, 3H), 4.90-4.97 (q, J = 6.3 Hz, 1H), 7.25-7.28 (m , 2H), 7.39-7.42 (m, 2H), 7.84-7.86 (m, 2H), 7.92-7.95 (m, 2H). IR cm <-1> : 3502, 2977, 1696, 1594, 1317, 1149,960, 771.
    [1174] The compounds of Examples 112-124 were prepared in a similar manner to the synthesis of Example 15.
    [1175] [Example 112] to [Example 124]
    [1176]
    [1177]
    [1178]
    [1179] The compounds of Examples 125-159 were prepared in a similar manner to Step 4 of Example 22.
    [1180] [Example 125] to [Example 159]
    [1181]
    [1182]
    [1183]
    [1184]
    [1185] The compounds of Examples 160-165 were prepared in a similar manner to the synthesis of Example 28.
    [1186] [Example 160] to [Example 165]
    [1187]
    [1188]
    [1189] Example 166
    [1190] 2,2-dimethyl-4- (3-fluorophenyl) -5- {4- (methylthio) phenyl} -3 ( 2H ) -Furanone
    [1191]
    [1192] Step 1: Preparation of 2- (3-fluorophenyl) -1- {4- (methylthio) phenyl} -ethanone
    [1193]
    [1194] To 68 ml of thianiazole was dissolved in 600 ml of dichloromethane at 0 ° C., aluminum chloride (77.3 g) and (3-fluorophenyl) acetyl chloride (100 g) were slowly and continuously added to the stirred solution. After stirring the reaction mixture for 1 hour, 1 L aqueous hydrochloric acid solution was slowly added to the reaction mixture. The mixture was stopped for 1 hour, and then extracted with methylene chloride. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The magnesium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure. The remaining residue was purified by recrystallization with hexane / dichloromethane to give 142.9 g of 2- (3-fluorophenyl) -1- {4- (methylthio) -phenyl} -ethanone. mp: 94.5-95.5 o C. NMR: δ 2.52 (s, 3H), 4.23 (s, 2H), 6.95-7.05 (m, 3H), 7.25-7.30 (m, 3H), 7.92 (d, J = 8.7 Hz, 2H).
    [1195] Step 2: 2,2-dimethyl-4- (3-fluorophenyl) -5- {4- (methylthio) phenyl} -3 ( 2H) -Production of Furanone
    [1196] To a solution of 2- (3-fluorophenyl) -1- {4- (methylthio) phenyl} -ethan-1-one (100 g) dissolved in anhydrous THF 1 liter and stirred, 26 g of 95% sodium hydride was added. Subsequently added at 0 o C. The reaction solution was stirred at the same temperature as above for 1 hour. 69 g of α -bromo-isobutyryl cyanide was diluted in 25 mL of anhydrous THF and then added dropwise to the stirred solution at 0 ° C. The reaction mixture was stirred overnight while slowly raising the temperature to room temperature. The solution was concentrated under reduced pressure, and then 50 ml of water was added. The aqueous layer was extracted with ethyl acetate (1 L). The organic layer was concentrated under reduced pressure, and then purified by column chromatography (hexane / ethyl acetate = 6: 1) to give 2,2-dimethyl-4- (3-fluorophenyl) -5- {4- (methylthio) phenyl } 102 g of 3 ( 2H ) -furanone were obtained. mp: 106 ° C. NMR: δ1.55 (s, 6H), 2.50 (s, 3H), 6.97-7.11 (m, 3H), 7.18 (d, J = 9.0 Hz, 2H), 7.26-7.36 (m , 1H), 7.55 (d, J = 9.0 Hz, 2H).
    [1197] The compounds of Examples 167-173 were prepared in a similar manner to the synthesis method in Example 166.
    [1198] Example 167 to Example 173
    [1199]
    [1200]
    [1201] Example 174
    [1202] 2,2-dimethyl-5- {4- (methylthio) phenyl} -4- (2-thienyl) -3 ( 2H ) -Furanone
    [1203]
    [1204] 2,2-dimethyl-5- {4- (methylthio) phenyl} -4- (2-thienyl) -3 ( 2H ) -furanone was synthesized in a similar manner to the synthesis in Example 166. mp: 113-114 ° C. NMR; δ 1.55 (s, 6H), 2.51 (s, 3H), 7.05 (dd, J = 5.1, 3.9 Hz, 1H), 7.11 (dd, J = 3.6, 1.2 Hz, 1H), 7.22 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 5.1 Hz, 1H), 7.68 (d, J = 9.0 Hz, 2H).
    [1205] Example 175
    [1206] 2,2-dimethyl-4- (fluorophenyl) -5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -Furanone
    [1207]
    [1208] Step 1: 4-bromo-2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -3 ( 2H) -Production of Furanone
    [1209]
    [1210] 2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone (135 mg) was dissolved in 25 ml of carbon tetrachloride, and then 1 ml of acetic acid and 0.1 ml of bromine were added dropwise. The reaction mixture was stirred at room temperature for 2.5 hours. 10 ml of saturated aqueous sodium thiosulfate solution was added to stop the reaction. The volatiles were removed under reduced pressure and then extracted with dichloromethane (50 mL x 3). The organic layer was dried over anhydrous magnesium sulfate, and the magnesium sulfate salt was filtered off. The filtrate was concentrated under reduced pressure, and the crude product was purified by column chromatography (hexane / ethyl acetate = 1/1) to give 4-bromo-2,2-dimethyl-5- {4- (methylsulfinyl) phenyl}. 68 mg of -3 ( 2H ) -furanone was obtained. mp: 117-118 o C. NMR: δ 1.55 (s, 6H), 2.79 (s, 3H), 7.81 (d, J = 8.2 Hz, 2H), 8.38 (d, J = 8.2 Hz, 2H). IR (cm -1 ): 1706, 1601, 1555, 1191, 1052.
    [1211] Step 2: 2,2-dimethyl-4- (4-fluorophenyl) -5- {4- (methylsulfinyl) phenyl} -3 ( 2H) -Production of Furanone
    [1212] Pd (Ph 3 ) 4 25 in a solution of 53 mg of 4-bromo-2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone dissolved in 30 ml of benzene. 25.4 mg of (4-fluorobenzene) boronic acid and 0.22 mL of 2M aqueous sodium carbonate solution were added. The reaction mixture was stirred at 80-90 ° C. for 12 hours. Thereafter, the reaction mixture was concentrated under reduced pressure, and the remaining residue was extracted with dichloromethane and brine. The organic layer was dried over anhydrous magnesium sulfate and then removed by evaporation under reduced pressure. The crude product was purified by column chromatography (hexane / ethyl acetate) to give 2,2-dimethyl-4- (4-fluorophenyl) -5- {4- (methylsulfinyl) phenyl} -3 ( 2H )- 15 mg of furanone was obtained. mp: 134-136 o C. NMR: δ 1.57 (s, 6H), 2.75 (s, 3H), 7.08 (m, 2H) 7.27 (m, 2H), 7.65 (d, J = 8.2 Hz, 2H), 7.80 (d, J = 8.2 Hz, 2H). IR (cm- 1 ): 2925, 2854, 1695, 1618, 1590, 1237, 1051, 758.
    [1213] Example 176
    [1214] 2,2-dimethyl-4- (3-fluorophenyl) -5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -Furanone
    [1215]
    [1216] Dissolve 2,2-dimethyl-4- (3-fluorophenyl) -5- {4- (methylthio) phenyl} -3 ( 2H ) -furanone (2.0 g, Example 166) in 50 ml of dichloromethane. To the stirred solution, 1.5 g of m -chloroperoxybenzoic acid was added at 0 ° C. The reaction solution was stirred at the same temperature as above for 1.5 hours, and then 30 ml of 5% aqueous sodium bicarbonate solution was added. The solution was stirred for another 10 minutes. The reaction mixture was concentrated under reduced pressure, and the remaining residue was extracted with 50 mL of water and dichloromethane (30 mL x 3). The organic layer was concentrated under reduced pressure, purified by column chromatography (hexane / ethyl acetate = 1: 1), and 2,2-dimethyl-4- (3-fluorophenyl) -5- {4- (methylsulfinyl) phenyl } -3 g ( 2H ) -furanone was obtained. mp: 143-144 o C. NMR: δ 1.58 (s, 6H), 2.76 (s, 3H), 7.26-7.08 (m, 3H), 7.30-7.38 (m, 1H), 7.65 (d, J = 8.2 Hz, 2H), 7.80 (d, J = 8.2 Hz, 2H).
    [1217] Example 177
    [1218] 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -Furanone
    [1219]
    [1220] 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone analogous to the synthesis method in Example 176 It was prepared by. mp: 133-134 o C. NMR: δ 1.57 (s, 6H), 2.77 (s, 3H), 6.75-6.87 (m, 3H), 7.69 (d, J = 8.2 Hz, 2H), 7.80 (d, J = 8.2 Hz, 2H).
    [1221] Example 178
    [1222] 4- (3-chloro-4-fluorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furan-3-thione
    [1223]
    [1224] 4- (3-chloro-4-fluorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone (Example 2) 90 mg toluene 30 Dissolve in mL and stir at reflux for 12 h in the presence of 60 mg Lawson's reagent. After the solvent was removed under reduced pressure, the remaining residue was extracted with 50 mL of water and ethyl acetate (50 mL x 3). The organic layer was concentrated under reduced pressure, purified by column chromatography (hexane / ethyl acetate = 4: 1), and the solid 4- (3-chloro-4-fluorophenyl) -2,2-dimethyl-5- {4- 30 mg of (methylsulfonyl) phenyl} -3 ( 2H ) -furan-3-thione was obtained. mp: 165-166 o C. NMR: δ 1.71 (s, 6H), 3.07 (s, 3H), 7.12 (m, 1H), 7.21 (d, 1H), 7.36 (dd, 1H), 7.81 (d, J = 8.4 Hz, 2H), 7.95 (d, J = 8.4 Hz, 2H). IR (cm -1 ): 1580, 1553, 1502, 1319, 1261, 1154, 957, 760.
    [1225] The compounds of Examples 179-181 were synthesized in a similar manner to the synthesis in Example 178.
    [1226] [Example 179] to [Example 181]
    [1227]
    [1228]
    [1229] Example 182
    [1230] 5- [4-{(acetylamino) sulfonyl} phenyl] -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -Furanone
    [1231]
    [1232] 360 mg of 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone (Example 129) were dissolved in 30 ml of dichloromethane. After the reaction, 0.5 ml of triethylamine and 50 mg of 4- (N, N-dimethylamino) pyridine were reacted with 0.8 ml of acetic anhydride for 12 hours at room temperature. The reaction mixture was concentrated under reduced pressure and extracted with 30 mL of water and dichloromethane (30 mL x 3). The organic layer was concentrated under reduced pressure, and then purified by column chromatography (hexane / ethyl acetate = 2: 1) to give a solid 5- [4-{(acetylamino) sulfonyl} phenyl] -2,2-dimethyl-4- (3 397 mg of -fluoro-phenyl) -3 ( 2H ) -furanone were obtained. mp: 178-179 o C. NMR: δ 1.57 (s, 6H), 2.08 (s, 3H), 7.05 (m, 3H), 7.34 (m, 1H), 7.82 (d, J = 8.4 Hz, 2H) , 8.05 (d, J = 8.4 Hz, 2H), 8.20 (br s, 1H). IR (cm- 1 ): 3198, 3238, 1698, 1431, 1261, 1159.
    [1233] Example 183
    [1234] 5- [4-{( n -Butyrylamino) sulfonyl} phenyl] -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -Furanone
    [1235]
    [1236] 360 mg of 5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone ( Example 129) were dissolved in 30 ml of dichloromethane. After the reaction, 0.5 ml of triethylamine and 50 mg of 4- (N, N-dimethylamino) pyridine were reacted with 0.8 ml of butyric anhydride for 12 hours at room temperature. The reaction mixture was concentrated under reduced pressure, and extracted with 30 mL of water and dichloromethane (30 mL x 3). The organic layer was concentrated under reduced pressure, and then purified by column chromatography (hexane / ethyl acetate = 2: 1) to give a solid 5- [4-{( n -butyrylamino) sulfonyl} phenyl] -2,2-dimethyl 363 mg of 4- (3-fluorophenyl) -3 ( 2H ) -furanone were obtained. mp: 188-189 o C. NMR: δ 0.89 (t, J = 7.5 Hz, 3H), 1.58 (s, 6H), 1.60 (m, 2H), 2.24 (t, J = 7.5 Hz, 2H), 7.05 (m, 3H), 7.34 (m, 1H), 7.82 (d, J = 8.4 Hz, 2H), 8.06 (d, J = 8.4 Hz, 2H), 8.19 (br s, 1H). IR (cm- 1 ): 3195, 3140, 1698, 1435, 1350, 1190.
    [1237] Example 184
    [1238] 2,2-dimethyl-5- {4- ( N -Methylaminosulfonyl) phenyl} -4- (3-fluorophenyl) -3 ( 2H ) -Furanone
    [1239]
    [1240] 500 mg of 2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -4- (3-fluorophenyl) -3 ( 2H ) -furanone (Example 166) was added 15 mg of trifluoroacetic anhydride. After stirring for 1 hour at 0 ° C. in mL, the solvent was removed under reduced pressure. The remaining residue was dissolved in 10 ml of a mixed solution of methanol / triethylamine 1: 1 and then stirred at 0 ° C. for 1 hour. The solution was concentrated under reduced pressure, and the remaining residue was stirred in 15 mL of dichloromethane, followed by addition of 5 mL of acetic acid saturated with chlorine. The solution was stirred at 0 ° C. for 30 minutes, then the solvent and unreacted chlorine were removed under reduced pressure. The remaining residue was dissolved in 5 ml of toluene and then the toluene was evaporated under reduced pressure. The remaining residue was dissolved in 20 mL of THF and reacted with 1 mL of 40% aqueous methylamine solution at 0 ° C. for 2 hours. The reaction solution was concentrated under reduced pressure, and extracted with 30 mL of water and dichloromethane (30 mL x 3). The organic layer was washed with brine, and then concentrated under reduced pressure. The remaining residue was purified by column chromatography (hexane / ethyl acetate = 3: 2) to give solid 2,2-dimethyl-5- {4- ( N -methylaminosulfonyl) phenyl} -4- (3- 155 mg of fluorophenyl) -3 ( 2H ) -furanone were obtained. mp: 176-177 o C. NMR: δ 1.58 (s, 6H), 2.70 (d, J = 5.1 Hz, 3H), 4.35 (q, J = 5.4 Hz, 1H), 7.04 (m, 3H), 7.33 (m, 1H), 7.89 (d, J = 8.7 Hz, 2H), 7.86 (d, J = 8.7 Hz, 2H). IR (cm- 1 ): 3285, 1696, 1402, 1388, 1261, 1160.
    [1241] Example 185
    [1242] 2,2-dimethyl-5- {4- ( N -Ethylaminosulfonyl) phenyl} -4- (3-fluorophenyl) -3 ( 2H ) -Furanone
    [1243]
    [1244] The title compound was prepared following the reaction procedure of Example 184, except for using an aqueous 70% ethylamine solution. mp: 113-114 o C. NMR: δ 1.13 (t, J = 7.2 Hz, 3H), 1.57 (s, 6H), 3.06 (m, 2H), 4.34 (t, J = 6.0 Hz, 1H), 7.03 (m, 3H), 7.32 (m, 1H), 7.78 (d, J = 8.7 Hz, 2H), 7.86 (d, J = 9.0 Hz, 2H). IR (cm- 1 ): 3271, 1694, 1619, 1592, 1387, 1260, 1159.
    [1245] The compounds of Examples 186-218 were prepared in a similar manner to the synthesis in step 6 of Example 31.
    [1246] [Example 186] to [Example 218]
    [1247]
    [1248]
    [1249]
    [1250]
    [1251]
    [1252] The compounds of Examples 219-226 were prepared by methods analogous to those in Example 34.
    [1253] Example 219 to Example 226
    [1254]
    [1255]
    [1256] The compounds of Examples 227-236 were prepared in a similar manner to the synthesis in Step 4 of Example 43.
    [1257] [Example 227] to [Example 236]
    [1258]
    [1259]
    [1260]
    [1261] Example 237
    [1262] 5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- (2-furanyl) -2-methyl-3 ( 2H ) -Furanone
    [1263]
    [1264] 5- {4- (aminosulfonyl) phenyl} -2-ethyl-4-iodine-2-methyl-3 ( 2H ) -furanone was combined with 2-furan boronic acid in a similar manner as in Example 44. mp: 154-155 o C. NMR: δ 0.92 (t, J = 7.5 Hz, 3H), 1.52 (s, 3H), 1.95 (m, 2H), 5.03 (br s, 2H), 6.51 (dd, J = 3.0, 1.8 Hz, 1H), 6.87 (d, J = 3.0 Hz, 2H), 7.37 (d, J = 1.5 Hz, 1H), 7.94 (d, J = 8.7 Hz, 2H), 8.02 (d, J = 8.7 Hz, 2H). IR (cm -1 ): 3347, 3257, 1692, 1545, 1341, 1164.
    [1265] The compounds of Examples 238 to 254 were prepared by methods analogous to those in step 6 of Example 47.
    [1266] Example 238 to Example 254
    [1267]
    [1268]
    [1269]
    [1270] The compounds of Examples 255 to 259 were prepared in a similar manner to the synthesis in Step 6 of Example 53.
    [1271] [Example 255] to [Example 259]
    [1272]
    [1273]
    [1274] Example 260
    [1275] 3- (3-methylphenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,5] dec-2-en-4-one
    [1276]
    [1277] 3- (3-methylphenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,5] dec-2-ene in a similar manner to the synthesis in step 6 of Example 56 4-one was prepared. mp: 154-155 o C. NMR: δ 1.82 (m, 10H), 2.34 (s, 3H), 3.06 (s, 3H), 6.99 (d, J = 8.4 Hz, 1H), 7.13 (m, 2H) , 7.25 (m, 1H), 7.86 (m, 2H), 7.93 (d, J = 8.7 Hz, 2H). IR (cm- 1 ): 2934, 1693, 1621, 1403, 1147, 1129, 716.
    [1278] Example 261
    [1279] 3- (3-fluorophenyl) -2- {4- (methylsulfonyl) phenyl} -1,8-dioxa-spiro [4,5] dec-2-en-4-one
    [1280]
    [1281] Step 1: 4-ethynyl-4-hydroxy-tetrahydro- ( 4H)-Preparation of Piran
    [1282]
    [1283] To 29.8 g of cerium (III) chloride dried at 140 ° C. and 0.1 torr for 2 hours, 200 ml of dry THF was added under argon. The suspension was stirred for 2 hours and then cooled to -78 ° C. To the stirred cerium chloride solution, 48 ml of 25% lithium acetylide / ethylene diamine dissolved in toluene solution was added dropwise over 30 minutes, followed by 10 g of tetrahydro- ( 4H ) -pyran-4-one in 100 ml of THF. Dissolved in water and added dropwise [Tetrahedron Lett. 25 , 4233 (1984). Then the temperature of the reaction mixture was slowly raised to room temperature and stirred for 18 hours. After stopping the reaction by adding a small amount of saturated aqueous ammonium chloride solution, the remaining material was dissolved by filtration through celite. The filtrate was concentrated under reduced pressure, and the remaining residue was extracted with brine and 200 ml of ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and then the magnesium sulfate was filtered off. The filtrate was concentrated to give 2.6 g of 4-ethynyl-4-hydroxy-tetrahydro- ( 4H ) -pyran. NMR: δ 1.77-1.86 (m, 2H), 1.91-1.99 (m, 2H), 2.51 (t, J = 6.0 Hz, 1H), 2.55 (s, 1H), 3.62-3.70 (m, 2H), 3.87 -4.00 (m, 2 H). IR (cm -1 ): 3388, 2960, 2865, 2109, 1717, 1338, 1085, 840.
    [1284] Step 2: 1- {4- (methylthio) phenyl} -4,4- {tetrahydro- ( 4H) -Pyranylidenyl} -2-butyne-1,4-diol
    [1285]
    [1286] In a solution of 4-ethynyl-4-hydroxy-tetrahydro- ( 4H ) -pyran (2 g) dissolved in 90 mL of dry THF and stirred, 21.8 mL of 1.6M butyllithium in hexane was added at -78 ° C. Slowly added. The mixture was stirred for 50 minutes and then p- (methylthio) benzaldehyde (2.41 g) was added. The temperature of the reaction solution was slowly raised to room temperature, followed by stirring for 2 hours. 100 ml of ice / water was added to stop the reaction, followed by extraction with 100 ml of methylene chloride. The organic layer was dried over anhydrous magnesium sulfate, and the magnesium sulfate was filtered off. The filtrate was concentrated under reduced pressure, and the remaining crude product was purified by column chromatography (hexane / ethyl acetate) to give 1- {4- (methylthio) phenyl} -4,4- {tetrahydro- ( 4H ) -pyranili 2.3 g of denyl} -2-butyne-1,4-diol were obtained. NMR: δ 1.79-1.88 (m, 2H), 2.20-2.35 (m, 2H), 2.50 (s, 3H), 3.61-3.70 (m, 2H), 3.83-3.88 (m, 2H), 4.40 (s, 1H), 5.49 (d, J = 6 Hz, 1H), 5.80 (s, 1H), 7.27 (d, J = 8.4 Hz, 2H), 7.45 (d, J = 8.4 Hz, 2H). IR (cm- 1 ): 3370, 2975, 2863, 2209, 1633, 1426, 1180, 743.
    [1287] Step 3: 4-hydroxy-1- {4- (methylthio) phenyl} -4,4- {4-tetrahydro- ( 4H) -Pyranylidenyl} -2-butyn-1-one
    [1288]
    [1289] Pyridinium dichromate (4.7 g) and 1- {4- (methylthio) -phenyl} -4,4- {4-tetrahydro- ( 4H ) -pyranylideneyl} -2-butyne-1,4-diol 2.3 g of the mixture was dissolved under 120 mL of dichloromethane, stirred at room temperature for 22 hours, and then 40 mL of ether was added. The reaction mixture was filtered through Florisil, and the filtrate was concentrated under reduced pressure. The crude product was purified by column chromatography (hexane / ethyl acetate) to give 4-hydroxy-1- {4- (methylthio) phenyl} -4,4- {4-tetrahydro- ( 4H ) -pyranylideneyl } 1.2 g of 2-butyn-1-one was obtained. NMR: δ 1.93-1.99 (m, 2H), 1.98-2.15 (m, 2H), 2.52 (s, 1H), 2.54 (s, 3H), 3.70-3.78 (m, 2H), 3.93-4.00 (m, 2H), 7.29 (d, J = 9.0 Hz, 2H), 8.02 (d, J = 9.0 Hz, 2H). IR (cm -1 ): 3400, 2957, 2862, 2208, 1568, 1263, 840.
    [1290] Step 4: Preparation of 2- {4- (methylthio) phenyl} -1,8-dioxa-spiro [4,5] dec-2-en-4-one
    [1291]
    [1292] 1.20 g of 4-hydroxy-1- {4- (methylthio) phenyl} -4,4- {4-tetrahydro- ( 4H ) -pyranylidenyl} -2-butyn-1-one in 170 ml of ethanol After dissolution, 0.48 g of diethylamine was added dropwise by diluting with 60 mL of ethanol. The mixture was stirred at rt for 1 h and then concentrated under reduced pressure. The remaining residue was extracted with water and dichloromethane (100 mL x 2), and then the organic layer was dried over anhydrous magnesium sulfate. The magnesium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure. The crude product was purified by column chromatography (hexane / ethyl acetate) to give solid 2- {4- (methylthio) phenyl} -1,8-dioxa-spiro [4,5] dec-2-ene-4 0.6 g of-temperature was obtained. mp: 135-138 o C. NMR: δ 1.58-1.63 (m, 2H), 2.07-2.18 (m, 2H), 2.55 (s, 3H), 3.81-3.91 (m, 2H), 4.04-4.10 (m , 2H), 5.97 (s, 1H), 7.32 (d, J = 9.0 Hz, 2H), 7.75 (d, J = 9.0 Hz, 2H). IR (cm- 1 ): 2954, 2860, 1691, 1598, 1583, 1468, 1096.
    [1293] Step 5: Preparation of 2- {4- (methylsulfonyl) phenyl} -1,8-dioxa-spiro [4,5] dec-2-en-4-one
    [1294]
    [1295] 2- {4- (methylthio) phenyl} -1,8-dioxa-spiro [4,5] dec-2-en-4-one (0.6 g) was dissolved in 10 ml of THF and 10 ml of ethanol and stirred To one solution, 2.67 g of oxone was dissolved in 5 ml of water and added. The mixture was stirred at rt for 26 h. After evaporating the volatile solvent under reduced pressure, the aqueous solution was extracted with dichloromethane. The organic layer was concentrated under reduced pressure, and the remaining crude product was purified by recrystallization with hexane / dichloromethane to give 2- {4- (methylsulfonyl) phenyl} -1,8-dioxa-spiro [4,5] dec-2 0.55 g of -en-4-one was obtained. mp: 163-165 o C. NMR: δ 1.58-1.70 (m, 2H), 2.09-2.20 (m, 2H), 3.11 (s, 3H), 3.82-3.92 (m, 2H), 4.04-4.14 (m , 2H), 6.16 (s, 1H), 8.05 (d, J = 8.7 Hz, 2H), 8.10 (d, J = 8.7 Hz, 2H). IR (cm- 1 ): 2862, 1694, 1314, 1152, 961.
    [1296] Step 6: Preparation of 3-iodine-2- {4- (methylsulfonyl) phenyl} -1,8-dioxa-spiro [4,5] dec-2-en-4-one
    [1297]
    [1298] 2- {4- (methylsulfonyl) phenyl} -1,8-dioxa-spiro [4,5] dec-2-en-4-one (0.55 g) in 50 ml of dichloromethane, [bis (trifluor Low acetoxy) iodide] benzene (0.84 g) and iodine (0.45 g) mixed solution were stirred at room temperature for 6 hours. Thereafter, 10 ml of saturated aqueous sodium thiosulfate solution was added to stop the reaction. The organic layer was washed with brine, and then concentrated under reduced pressure. The remaining crude product was purified by column chromatography (hexane / ethyl acetate) to give 3-iodine-2- {4- (methylsulfonyl) phenyl} -1,8-dioxa-spiro [4,5] dec-2 0.6 g of -en-4-one was obtained. mp: 210-213 o C. NMR: δ 1.60-1.72 (m, 2H), 2.11-2.44 (m, 2H), 3.12 (s, 3H), 3.80-3.90 (m, 2H), 4.04-4.14 (m , 2H), 8.21 (d, J = 9 Hz, 2H), 8.41 (d, J = 9 Hz, 2H). IR (cm -1 ): 1690, 1580, 1146, 912, 744.
    [1299] Step 7: Preparation of 3- (3-fluorophenyl) -2- {4- (methylsulfonyl) phenyl} -1,8-dioxa-spiro [4,5] dec-2-en-4-one
    [1300] 120 mg of 3-iodine-2- {4- (methylsulfonyl) phenyl} -1,8-dioxa-spiro [4,5] dec-2-en-4-one in 5 ml of toluene and 5 ml of ethanol To the solution which was dissolved and stirred, 16 mg of tetrakis (triphenylphosphine) palladium (0), 0.3 ml of 2M aqueous sodium carbonate solution and 43 mg of 3-fluorobenzeneboronic acid were added at room temperature. The reaction mixture was stirred at 100 ° C. for 3 hours and purified in a similar manner to the method used in Example 2, where 3- (3-fluorophenyl) -2- {4- (methylsulfonyl) phenyl} 84 mg of -1,8-dioxa-spiro [4,5] dec-2-en-4-one was obtained. mp: 164-166 o C. NMR: δ 1.70-1.75 (m, 2H), 2.15-2.26 (m, 2H), 3.09 (s, 3H), 3.84-3.94 (m, 2H), 4.08-4.14 (m , 2H), 7.02-7.10 (m, 3H), 7.31-7.40 (m, 1H), 7.86 (d, J = 8.4 Hz, 2H), 7.97 (d, J = 8.4 Hz, 2H). IR (cm −1 ): 2862, 1694, 1623, 1430, 1318, 1148, 1103, 770.
    [1301] The compounds of Examples 262 and 263 were prepared in a manner similar to the synthesis in step 7 of Example 261.
    [1302] Example 262 and Example 263
    [1303]
    [1304]
    [1305] Example 264
    [1306] 2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -4-phenyl-3 ( 2H ) -Furanone
    [1307]
    [1308] Step 1: Preparation of 1- {3-fluoro-4- (methylthio) phenyl} -2-phenyl-ethan-1-one
    [1309]
    [1310] 1.5 g of 2-fluorothioanisole was dissolved in 50 ml of dichloromethane, and 1.2 g of aluminum chloride and 1 ml of phenylacetyl chloride were added to the stirred solution at 0 ° C. The reaction mixture was stirred at rt for 12 h. Thereafter, an appropriate amount of ice and hydrochloric acid was added to stop the reaction. The mixture was quenched with dichloromethane (50 mL x 3) and the organic layer was washed with brine. The organic layer was dried over anhydrous magnesium sulfate, and the magnesium sulfate was filtered off. The filtrate was concentrated under reduced pressure and recrystallized with methanol to obtain 1.8 g of purified 1- {3-fluoro-4- (methylthio) phenyl} -2-phenyl-ethan-1-one. mp: 71-72 ° C. NMR: δ 2.50 (s, 3H), 4.22 (s, 2H), 7.20-7.33 (m, 6H), 7.64 (m, 1H), 7.77 (m, 1H).
    [1311] Step 2: 2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -4-phenyl-3 ( 2H) -Production of Furanone
    [1312] 1- {3-fluoro-4- (methylthio) phenyl} -2-phenyl-ethan-1-one (1.68 g) was dissolved in 100 ml of anhydrous THF and stirred in a 60% sodium hydride oil dispersion ( 270 mg) was added dropwise at 0 ° C in portions. After the reaction solution was stirred at the same temperature for 1 hour, 1.2 mL of α-bromo-isobutyryl cyanide diluted with 25 mL of anhydrous THF was added dropwise to the stirring solution at 0 ° C. The reaction mixture was stirred overnight while gradually raising the temperature to room temperature. The solution was concentrated under reduced pressure and 50 ml of water was added. The aqueous solution was extracted with dichloromethane (50 mL × 3). The organic layer was concentrated under reduced pressure, and then purified by column chromatography (hexane / ethyl acetate = 6: 1) to give 2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -4-phenyl 1.21 g of -3 ( 2H ) -furanone were obtained. NMR: δ 1.55 (s, 6H), 2.48 (s, 3H), 7.26-7.39 (m, 7H), 7.67 (m, 1H), 7.81 (m, 1H). IR cm <-1> : 1696, 1421, 1388, 1238.
    [1313] The compounds of Examples 265-272 were synthesized in a similar manner to the series of methods used for the synthesis of Example 264.
    [1314] [Example 265] to [Example 272]
    [1315]
    [1316]
    [1317]
    [1318] Example 273
    [1319] 2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -4-phenyl-3 ( 2H ) -Furanone
    [1320]
    [1321] 2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -4-phenyl-3 ( 2H ) -furanone (1.21 g: Example 264) was added methanol / THF / water 1: After dissolving in 150 ml of 1: 1 mixed solution, 2.77 g of oxone was added thereto. The mixture was stirred for 4 hours at room temperature. The volatile solvent was removed under reduced pressure, and the remaining solution was diluted with 50 mL of water. The aqueous solution was extracted with dichloromethane (30 mL x 3). The organic layer was concentrated under reduced pressure, purified by column chromatography (hexane / ethyl acetate = 4: 1), and solid 2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -4 520 mg of -phenyl-3 ( 2H ) -furanone was obtained. mp: 190-191 o C. NMR: δ 1.55 (s, 6H), 3.23 (s, 3H), 7.26 (m, 2H), 7.38 (m, 3H), 7.56 (m, 2H), 7.92 (m, 1H). IR (cm- 1 ): 1700, 1427, 1324, 1160, 1147. MS (FAB): 361 ( m + 1).
    [1322] The compounds of Examples 274-287 were synthesized in a similar manner to those in Example 273.
    [1323] [Example 274] to [Example 287]
    [1324]
    [1325]
    [1326]
    [1327] Example 288
    [1328] 4- (4-aminophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [1329]
    [1330] 200 mg of 2,2-dimethyl-4- (4-nitrophenyl) -5- {3-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone (Example 287) After dissolving in ml and 1 ml of water, 0.5 ml of concentrated hydrochloric acid and 0.2 g of Fe powder were added. The mixture was stirred at 70 ° C. for 12 hours. After the reaction mixture was cooled to room temperature, unreacted Fe was filtered off. The filtrate was concentrated under reduced pressure, and the remaining residue was neutralized with 1N aqueous sodium hydroxide solution, and then extracted with 30 mL of dichloromethane. The organic layer was concentrated under reduced pressure, purified by column chromatography (hexane / ethyl acetate = 1: 1), and the solid 4- (4-aminophenyl) -2,2-dimethyl-5- {3-fluoro-4- 102 mg of (methylsulfonyl) phenyl} -3 ( 2H ) -furanone were obtained. mp: 199-200 o C. NMR: δ 1.54 (s, 6H), 3.24 (s, 3H), 3.80 (br s, 2H), 6.71 (d, J = 8.7 Hz, 2H), 7.06 (d, J = 8.7 Hz, 2H), 7.61 (dd, J = 10.5, 1.8 Hz, 1H), 7.64 (dd, J = 8.4, 1.8 Hz, 1H), 7.92 (dd, J = 8.1, 7.2 Hz, 1H). IR (cm- 1 ): 3468, 3374, 1694, 1517, 1386, 1320, 1159, 1147.
    [1331] Example 289
    [1332] 4- {4- N -(Acetylamino) phenyl} -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [1333]
    [1334] 60 mg of 4- (4-aminophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone (Example 288), N In the presence of 10 mg of N-dimethylaminopyridine, it was reacted with 0.2 ml of acetic anhydride dissolved in 10 ml of dichloromethane and 0.5 ml of triethylamine for 12 hours at room temperature. The solvent was evaporated under reduced pressure, and the remaining residue was extracted with 30 mL of water and 30 mL of dichloromethane. The organic layer was concentrated under reduced pressure, and then purified by column chromatography (hexane / ethyl acetate = 1: 1) to obtain solid 4- {4- N- (acetylamino) phenyl} -2,2-dimethyl-5- {3. 38 mg of -fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone were obtained. mp: 170-171 ° C. NMR: δ 1.57 (s, 6H), 2.21 (s, 3H), 3.25 (s, 3H), 7.23 (d, J = 9.9 Hz, 2H), 7.56 (m, 3H), 7.60 (dd, J = 8.4 , 1.8 Hz, 1H), 7.93 (dd, J = 7.8, 7.2 Hz, 1H). IR (cm- 1 ) 3335, 1697, 1596, 1524, 1319, 1159, 1147.
    [1335] Example 290
    [1336] 2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -4- (3-fluorophenyl) -3 ( 2H ) -Furanone
    [1337]
    [1338] 2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -4- (3-fluorophenyl) -3 ( 2H ) prepared in a similar manner to that used in Example 264 To furanone (1.6 g) was dissolved in 50 ml of dichloromethane and stirred, 1.25 g of m -chloroperoxybenzoic acid was added at 0 ° C. The reaction solution was stirred at the above temperature for 1.5 hours, 30 ml of 5% aqueous sodium bicarbonate solution was added to the solution, followed by further stirring for 10 minutes. The reaction mixture was concentrated under reduced pressure, and the remaining residue was extracted with 50 ml of water and dichloromethane (30 ml × 3). The organic layer was concentrated under reduced pressure, and then purified by column chromatography (hexane / ethyl acetate = 1: 1) to obtain solid 2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl}-. 1.6 g of 4- (3-fluorophenyl) -3 ( 2H ) -furanone were obtained. mp: 148-149 o C. NMR: δ 1.58 (s, 6H), 2.87 (s, 3H), 7.06 (m, 3H), 7.36 (m, 1H), 7.42 (dd, J = 10.5, 1.8 Hz, 1H), 7.66 (dd, J = 8.4, 1.8 Hz, 1H), 7.87 (dd, J = 8.1, 6.9 Hz, 1H). IR (cm −1 ): 1700, 1623, 1420, 1261, 1216, 1192, 1135, 1077.
    [1339] The compounds of Examples 291-299 were synthesized in a manner similar to the method used in the synthesis of Example 290.
    [1340] [Example 291] to [Example 299]
    [1341]
    [1342]
    [1343] Example 300
    [1344] 5- {4- (aminosulfonyl) -3-fluorophenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -Furanone
    [1345]
    [1346] 220 mg of 2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -4-phenyl-3 ( 2H ) -furanone (Example 291), trifluoroacetic anhydride 30 Dissolve in mL and stir at 0 ° C. for 2 h. The volatiles were removed under reduced pressure, and 30 ml of methanol and triethylamine 1: 1 mixed solution was added to the remaining residue. The solution was concentrated under reduced pressure, and the remaining residue was dissolved in 30 mL of dichloromethane, followed by the slow addition of 5 mL of acetic acid saturated with chlorine. The reaction mixture was stirred at room temperature for 5 minutes and then the volatiles were removed under reduced pressure. The remaining residue was dissolved in 30 ml of toluene and then concentrated under reduced pressure again. The residue was diluted with 30 mL of THF and reacted with 3 mL of aqueous ammonia solution at room temperature overnight. The reaction solution was concentrated under reduced pressure, and the remaining residue was extracted with 30 mL of water and dichloromethane (30 mL × 3). The organic layer was concentrated under reduced pressure, and then purified by column chromatography (hexane / ethyl acetate = 3: 2) to give 5- {4- (aminosulfonyl) -3-fluorophenyl} -2,2-dimethyl-4- 65 mg of phenyl-3 ( 2H ) -furanone were obtained. NMR: δ 1.57 (s, 6H), 5.11 (br s, 2H), 7.27 (m, 2H), 7.40 (m, 3H), 7.52 (m, 2H), 7.86 (dd, J = 8.1, 6.9 Hz, 1H). IR (cm- 1 ): 3404, 3227, 1685, 1560, 1356, 1150. MS (FAB): 362 ( m + 1).
    [1347] The compounds of Examples 301-313 were prepared in a similar manner to the method used in the synthesis of Example 300.
    [1348] [Example 301] to [Example 313]
    [1349]
    [1350]
    [1351]
    [1352] Example 314
    [1353] 2,2-dimethyl-5- {2-fluoro-4- (methylthio) phenyl} -4-phenyl-3 ( 2H ) -Furanone
    [1354]
    [1355] 1- {2-fluoro-4- (methylthio) phenyl} -2-phenyl-ethan-1-one (675 mg) prepared in a similar manner to step 1 of Example 264 was dissolved in 50 mL of dry THF and 120 mg of sodium hydride was added. The reaction mixture was stirred at 0 ° C. for 1 hour and then 0.35 ml of α-bromoisobutyryl cyanide diluted with 20 ml THF was added dropwise. The reaction mixture was stirred overnight while raising the temperature to room temperature. The reaction solvent was removed under reduced pressure, and the remaining residue was extracted with 50 mL of water and dichloromethane (30 mL × 3). The organic layer was concentrated under reduced pressure, and then purified by column chromatography (hexane / ethyl acetate = 6: 1) to give 2,2-dimethyl-5- {2-fluoro-4- (methylthio) phenyl} -4-phenyl 353 mg of -3 ( 2H ) -furanone were obtained. NMR: δ 1.54 (s, 6H), 2.49 (s, 3H), 6.90 (dd, J = 10.8, 1.8 Hz, 1H), 7.00 (dd, J = 8.4, 1.8 Hz, 1H), 7.22-7.29 (m , 5H), 7.40 (dd, J = 8.4, 7.2 Hz, 1H). IR (cm −1 ): 1699, 1610, 1388, 1175, 1049.
    [1356] The compounds of Examples 315-320 were synthesized in a similar manner to the synthesis of Example 314.
    [1357] [Example 315] to [Example 320]
    [1358]
    [1359]
    [1360] Example 321
    [1361] 2,2-dimethyl-5- {2-fluoro-4- (methylsulfonyl) phenyl} -4-phenyl-3 ( 2H ) -Furanone
    [1362]
    [1363] 305 mg of 2,2-dimethyl-5- {2-fluoro-4- (methylthio) phenyl} -4-phenyl-3 ( 2H ) -furanone (Example 314) was charged with 30 ml of methanol, 20 ml of THF and After dissolving in 20 ml of water, 1.4 g of oxone was added thereto. The reaction mixture was stirred at rt overnight. After the solvent was removed under reduced pressure, the remaining residue was extracted with 50 mL of water and dichloromethane (30 mL x 3). The organic layer was concentrated under reduced pressure, and then purified by column chromatography (hexane / ethyl acetate = 3: 2) to obtain solid 2,2-dimethyl-5- {2-fluoro-4- (methylsulfonyl) phenyl}- 70 mg of 4-phenyl-3 ( 2H ) -furanone was obtained. mp: 175-176 o C. NMR: δ 1.57 (s, 6H), 3.10 (s, 3H), 7.22 (m, 2H), 7.28 (m, 3H), 7.75 (dd, J = 8.7, 1.8 Hz, 1H), 7.77 (m, 2H). IR (cm- 1 ): 1702, 1408, 1321, 1147. MS (FAB): 361 ( m + 1).
    [1364] The compounds of Examples 322-326 were prepared by methods similar to those of Example 321.
    [1365] [Example 322] to [Example 326]
    [1366]
    [1367]
    [1368] Example 327
    [1369] 2,2-dimethyl-5- {2-fluoro-4- (methylsulfinyl) phenyl} -4-phenyl-3 ( 2H ) -Furanone
    [1370]
    [1371] 241 mg of 2,2-dimethyl-5- {2-fluoro-4- (methylthio) phenyl} -4-phenyl-3 ( 2H ) -furanone (Example 314) was dissolved in 50 ml of dichloromethane. 138 mg, 70% m -chloroperoxybenzoic acid was added. The mixture was stirred for 1.5 h at 0 ° C., then 30 ml of 5% aqueous sodium bicarbonate solution was added. The mixture was then stirred for 10 minutes and the volatiles were removed under reduced pressure. The residue was extracted with 50 mL of water and dichloromethane (30 mL x 3). The organic layer was concentrated under reduced pressure, and then purified by column chromatography separation (hexane / ethyl acetate = 1: 1) to give a solid 2,2-dimethyl-5- {2-fluoro-4- (methylsulfinyl) phenyl } 187 mg of 4-phenyl-3 ( 2H ) -furanone were obtained. mp: 149-150 o C. NMR: δ 1.55 (s, 6H), 2.78 (s, 3H), 7.26 (m, 5H), 7.47 (m, 2H), 7.69 (dd, J = 8.4, 6.6 Hz, 2H). IR (cm -1 ): 1700, 1621, 1380, 1223, 1161, 1075.
    [1372] The compounds of Examples 328-331 were synthesized in a similar manner to the synthesis method used in Example 327.
    [1373] [Example 328] to [Example 331]
    [1374]
    [1375]
    [1376] Example 332
    [1377] 5- {4- (aminosulfonyl) -2-fluorophenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -Furanone
    [1378]
    [1379] 2,2-dimethyl-5- {2-fluoro-4- (methylsulfinyl) phenyl} -4-phenyl-3 (2H) -Furanone (Example 327) 154 mg was dissolved in 30 ml of anhydrous trifluoroacetic acid and stirred at 0 ° C. for 2 hours. After the volatiles were removed under reduced pressure, 50 mL of a 1: 1 mixed solution of methanol and triethylamine was added. After the solution was stirred at 0 ° C. for 20 minutes, the solvent was removed under reduced pressure. The remaining residue was dissolved in 40 mL of dichloromethane and 15 mL of acetic acid saturated with chlorine was added dropwise. The reaction solution was stirred at 0 ° C. for 20 minutes. Since chlorine did not react with the solvent was removed under reduced pressure. The remaining residue was dissolved in 30 ml of toluene and the toluene was evaporated under reduced pressure. The remaining residue was then dissolved in 40 mL of THF and reacted with 5 mL of ammonia water with stirring overnight. The solvent was removed under reduced pressure, and the remaining residue was extracted with 30 mL of water and dichloromethane (30 mL x 3). The organic layer was concentrated under reduced pressure, and then purified by column chromatography (hexane / ethyl acetate = 3: 2) to obtain solid 5- {4- (aminosulfonyl) -2-fluorophenyl} -2,2-dimethyl- 4-phenyl-3 (2H42 mg of furanone were obtained. mp: 79-81oC. NMR: δ 1.58 (s, 6H), 5.01 (br s, 2), 7.20-7.31 (m, 5H), 7.69-7.76 (m, 3H). IR (cm-One): 3340, 3274, 1591, 1526, 1328. MS (FAB): 362 (m + 1).
    [1380] The compounds of Examples 333-335 were synthesized in a manner similar to that used in Example 332.
    [1381] [Example 333] to [Example 335]
    [1382]
    [1383]
    [1384] Example 336
    [1385] 5- {3-bromo-4- (methylthio) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -Furanone
    [1386]
    [1387] 232 mg of 60% sodium hydride oil dispersion in a solution of 1- {3-bromo-4- (methylthio) phenyl} -2-phenyl-ethan-1-one (1.54 g) dissolved in 50 ml of THF and stirred Was added. The mixture was stirred for 1 h at 0 ° C. and 1.1 ml of α-bromoisobutyryl cyanide diluted with 20 ml THF was added dropwise. The reaction mixture was slowly raised to room temperature and stirred overnight. The solvent was removed under reduced pressure, and the remaining residue was extracted with 50 mL of water and dichloromethane (30 mL x 3). The organic layer was concentrated under reduced pressure, purified by column chromatography (hexane / ethyl acetate = 6: 1), and 5- {3-bromo-4- (methylthio) phenyl} -2,2-dimethyl-4-phenyl- 1.1 g of 3 ( 2H ) -furanone was obtained. NMR: δ 1.55 (s, 6H), 2.47 (s, 3H), 6.99 (d, J = 8.7 Hz, 1H), 7.32 (m, 5H), 7.48 (dd, J = 8.7, 2.1 Hz, 1H), 7.88 (d, J = 1.8 Hz, 1H).
    [1388] The compounds of Examples 337-340 were prepared by methods analogous to those in Example 336.
    [1389] [Example 337] to [Example 340]
    [1390]
    [1391]
    [1392] Example 341
    [1393] 5- {3-bromo-4- (methylsulfonyl) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -Furanone
    [1394]
    [1395] 350 mg of 5- {3-bromo-4- (methylthio) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone (Example 336) were dissolved in 50 ml of methanol, THF and water, respectively. The solution was dissolved in a mixed solution of and then reacted with 1.5 g of oxone while stirring at room temperature for 15 hours. The solvent was then removed under reduced pressure, and the remaining residue was extracted with 50 mL of water and dichloromethane (30 mL x 3). The organic layer was concentrated under reduced pressure, purified by column chromatography (hexane / ethyl acetate = 3: 2), and the solid 5- {3-bromo-4- (methylsulfonyl) phenyl} -2,2-dimethyl-4 173 mg of -phenyl-3 ( 2H ) -furanone was obtained. mp: 154-155 o C. NMR: δ 1.58 (s, 6H), 3.29 (s, 3H), 7.26 (m, 3H), 7.38 (m, 2H), 8.07 (d, J = 1.8 Hz, 1H) , 8.10 (d, J = 8.1 Hz, 2H). IR (cm- 1 ): 1698, 1585, 1318, 1150.
    [1396] The compounds of Examples 342-345 were synthesized in a manner similar to that used in Example 341.
    [1397] [Example 342] to [Example 345]
    [1398]
    [1399]
    [1400] Example 346
    [1401] 5- {3-bromo-4- (methylsulfinyl) phenyl} -2,2-dimethyl-4-phenyl-3 (2 H ) -Furanone
    [1402]
    [1403] 5- {3-bromo-4- (methylthio) phenyl} -2,2-dimethyl-4-phenyl-3 (2H) -Furanone (Example 336) 391 mg were dissolved in 50 ml of dichloromethane, then 183 mg of 70% m-chloroperoxybenzoic acid was added and stirred at 0 ° C. for 50 minutes. 10 ml of 5% aqueous sodium hydroxide solution was added to the reaction mixture, which was further stirred for 10 minutes. After dichloromethane was removed under reduced pressure, the remaining residue was extracted with 50 mL of water and dichloromethane (30 mL x 3). The organic layer was concentrated under reduced pressure, and then purified by column chromatography (hexane / ethyl acetate = 1: 1) to give 5- {3-bromo-4- (methylsulfinyl) phenyl} -2,2-dimethyl-4- Phenyl-3 (2H310 mg of) -furanone were obtained. NMR: δ 1.58 (s, 6H), 2.84 (s, 3H), 7.30 (m, 2H), 7.38 (m, 3H), 7.78 (dd,J =8.4, 1.8 Hz, 1H), 7.88 (d,J =5.4 Hz, 1H), 7.90 (d,J =2.7 Hz, 1H). IR (cm-One): 1698, 1619, 1388, 1064.
    [1404] The compounds of Examples 347-350 were prepared by methods similar to those disclosed in Example 346.
    [1405] [Example 347] to [Example 350]
    [1406]
    [1407]
    [1408] Example 351
    [1409] 5- {4- (aminosulfonyl) -3-bromophenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -Furanone
    [1410]
    [1411] 287 mg of 5- {3-bromo-4- (methylsulfinyl) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone (Example 346) 40 ml of anhydrous trifluoroacetic acid Dissolved in and stirred at 0 ° C. for 1 h. The solvent was then removed under reduced pressure, and the remaining residue was dissolved in 50 mL of a 1: 1 mixed solution of methanol and triethylamine. The solution was stirred at 0 ° C. for 1 h and then the solvent was removed under reduced pressure. The remaining residue was stirred in 30 mL of dichloromethane and then 15 mL of acetic acid saturated with chlorine was added dropwise. The reaction solution was stirred at 0 ° C. for 30 minutes. Acetic acid and unreacted chlorine were evaporated under reduced pressure. The remaining residue was stirred overnight in 30 mL of THF and 5 mL of ammonia water. The reaction mixture was concentrated under reduced pressure and extracted with 30 mL of water and dichloromethane (30 mL x 3). The organic layer was concentrated under reduced pressure, and then purified by column chromatography (hexane / ethyl acetate = 3: 2) to obtain solid 5- {4- (aminosulfonyl) -3-bromophenyl} -2,2-dimethyl- 89 mg of 4-phenyl-3 ( 2H ) -furanone was obtained. mp: 128-132 o C. NMR: δ 1.63 (s, 6H), 5.32 (br s, 2H), 7.12 (m, 2H), 7.40 (m, 3H), 7.69 (m, 1H), 7.98 (m , 2H). IR (cm- 1 ): 3400, 3282, 1686, 1556, 1171.
    [1412] The compounds of Examples 352 to 353 were prepared in a similar manner to the preparation of Example 351.
    [1413] [Example 352] to [Example 353]
    [1414]
    [1415]
    [1416] Example 354
    [1417] 5- {3-chloro-4- (methylthio) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -Furanone
    [1418]
    [1419] Step 1: Preparation of 1- {3-chloro-4- (methylthio) phenyl} -2-phenyl-ethanone
    [1420]
    [1421] 2-chlorothioanisole (3.0 g) was dissolved in 120 ml of dichloromethane and stirred. The solution was first added slowly 2.8 g of aluminum chloride and then 3.0 g of phenylacetyl chloride at 0 ° C. The reaction mixture was stirred at this temperature for 12 hours. Thereafter, the reaction solution was poured into ice and hydrochloric acid aqueous solution, and the reaction was stopped for 30 minutes, and then extracted with dichloromethane (80 mL × 3). The organic layer was washed with brine and dried over anhydrous magnesium sulfate. After magnesium sulfate was filtered off, the filtrate was concentrated under reduced pressure. The remaining residue was recrystallized from hexane and dichloromethane to give 3.6 g of 1- {3-chloro-4- (methylthio) phenyl} -2-phenyl-ethan-1-one. mp: 101-102 o C. NMR: δ 2.51 (s, 3H), 4.22 (s, 2H), 7.17 (d, J = 8.4 Hz, 1H), 7.25 (m, 3H), 7.32 (m, 2H) , 7.87 (dd, J = 8.4, 1.8 Hz, 1H), 7.97 (d, J = 1.8 Hz, 1H).
    [1422] Step 2: 5- {3-chloro-4- (methylthio) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H) -Production of Furanone
    [1423] 3.6 g of 1- {3-chloro-4- (methylthio) phenyl} -2-phenyl-ethan-1-one are dissolved in 100 mL of anhydrous THF and 0 in the presence of 60% sodium hydride oil dispersion (1.5 g). Stir at 20 ° C. for 20 minutes. Thereafter, α-bromoisobutyryl cyanide (3.0 mL) diluted with 50 mL THF was added dropwise. The temperature of the reaction solution was slowly raised to room temperature and then stirred overnight. The solvent was then removed under reduced pressure and extracted with 30 mL of water and diethyl ether (50 mL × 3). The organic layer was concentrated under reduced pressure, purified by column chromatography (hexane / ethyl acetate = 8: 1), and 5- {3-chloro-4- (methylthio) phenyl} -2,2-dimethyl-4-phenyl-3 3.2 g of ( 2H ) -furanone were obtained. NMR: δ 1.52 (s, 6H), 2.45 (s, 3H), 7.17 (d, J = 8.4 Hz, 1H), 7.25 (m, 3H), 7.32 (m, 2H), 7.87 (dd, J = 8.4 , 1.8 Hz, 1H), 7.97 (d, J = 1.8 Hz, 1H). IR (cm −1 ): 1694, 1613, 1592, 1389, 1252, 1145, 1128.
    [1424] The compounds of Examples 355-356 were prepared by methods similar to those used in Example 354.
    [1425] [Example 355] to [Example 356]
    [1426]
    [1427]
    [1428] Example 357
    [1429] 5- {3-chloro-4- (methylsulfonyl) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -Furanone
    [1430]
    [1431] 1.2 g of 5- {3-chloro-4- (methylthio) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone (Example 354) was added to methanol / THF / water 1: 1: After dissolving in 150 ml of the mixed solution of 1, 2.8 g of oxone was added thereto. The reaction mixture was stirred for 6 hours at room temperature. The reaction mixture was concentrated under reduced pressure, and the remaining residue was extracted with 50 ml of water and ethyl acetate (100 ml x 3). The organic layer was concentrated under reduced pressure, purified by column chromatography (hexane / ethyl acetate = 3: 1) and solid. 1.1 g of 5- {3-chloro-4- (methylsulfonyl) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone was obtained. mp: 174-175 o C. NMR: δ 1.58 (s, 6H), 3.28 (s, 3H), 7.27 (m, 3H), 7.39 (m, 2H), 7.66 (dd, J = 8.4, 1.8 Hz, 1H), 7.86 (d, J = 1.8 Hz, 1H), 8.09 (d, J = 8.4 Hz, 1H). IR (cm- 1 ): 1700, 1587, 1391, 1321, 1241, 1152.
    [1432] The compounds of Examples 358-362 were prepared by methods similar to those in Example 357.
    [1433] Example 358 to Example 362
    [1434]
    [1435]
    [1436]
    [1437] Example 363
    [1438] 5- {3-chloro-4- (methylsulfinyl) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -Furanone
    [1439]
    [1440] 5- {3-chloro-4- (methylthio) phenyl} -2,2-dimethyl-4-phenyl-3 (2H) -Furanone (Example 354) 3.5 g was dissolved in 80 ml of dichloromethane and stirred in a solution of 70%m2.5 g of chloroperoxybenzoic acid were added and stirred at 0 ° C for 2 h. 40 ml of 5% aqueous sodium bicarbonate solution was added to the solution and stirred for a further 10 minutes. The solution was extracted with dichloromethane (50 mL × 3). The organic layer was concentrated under reduced pressure, purified by column chromatography (hexane / ethyl acetate = 1: 1), and the solid 5- {3-chloro-4- (methylsulfinyl) phenyl} -2,2-dimethyl-4- Phenyl-3 (2H2.43 g of) -furanone were obtained. mp: 120-121oC. NMR: δ 1.57 (s, 6H), 2.84 (s, 3H), 7.30 (m, 3H), 7.38 (m, 2H), 7.72 (s, 1H), 7.74 (d,J =8.1 Hz, 1H), 7.91 (d,J =8.1 Hz, 1H). IR (cm-One): 1699, 1619, 1319, 1239, 1169, 1145, 1068.
    [1441] The compounds of Examples 364-366 were synthesized using methods similar to those in Example 363.
    [1442] [Example 364] to [Example 366]
    [1443]
    [1444]
    [1445] Example 367
    [1446] 5- {4- (aminosulfonyl) -3-chlorophenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -Furanone
    [1447]
    [1448] 5- {3-chloro-4- (methylsulfinyl) phenyl} -2,2-dimethyl-4-phenyl-3 (2H) -Furanone (Example 363) 1.2 g was stirred in 30 ml of anhydrous trifluoroacetic acid at 0 ° C. for 2 hours. After the solvent was removed under reduced pressure, 30 ml of a 1: 1 mixed solution of methanol / triethylamine was added to the remaining residue. The mixture was stirred at 0 ° C. for 1 hour and the solvent was removed under reduced pressure. After the remaining residue was dissolved, 30 ml of acetic acid saturated with chlorine were added. The reaction mixture was stirred at 0 ° C. for 30 minutes. Thereafter, the solvent and unreacted chlorine were evaporated under reduced pressure, and the remaining residue was stirred in 30 ml of THF and 3 ml of ammonia water overnight. The reaction mixture was concentrated under reduced pressure, and the remaining residue was extracted with 30 mL of water and dichloromethane (30 mL x 3). The organic layer was washed with brine, and then concentrated under reduced pressure. The remaining residue was purified by column chromatography (hexane / ethyl acetate = 3: 2) to give solid 5- {4- (aminosulfonyl) -3-chlorophenyl} -2,2-dimethyl-4-phenyl- 3 (2H512 mg of) -furanone was obtained. mp: 193-194oC. NMR: δ 1.58 (s, 6H), 5.14 (br s, 2H), 7.26 (m, 3H), 7.39 (m, 2H), 7.62 (dd,J =8.4, 1.8 Hz, 1H), 7.84 (d,J =1.8 Hz, 1H), 8.04 (d,J =8.1 Hz, 1H). IR (cm-One): 3379, 3263, 1691, 1586, 1347,1219, 1156.
    [1449] The compounds of Examples 368 to 371 were prepared by methods similar to those in Example 367.
    [1450] Example 368 to Example 371
    [1451]
    [1452]
    [1453]
    [1454] Example 372
    [1455] 5- {3-chloro-4- (N-methylaminosulfonyl) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -Furanone
    [1456]
    [1457] 2,2-dimethyl-5- {3-chloro-4- (methylsulfinyl) phenyl} -4-phenyl-3 (2H) -Furanone (Example 363) After stirring 200 mg in 10 ml of anhydrous trifluoroacetic acid at 0 ° C. for 1 hour, the solvent was removed under reduced pressure. The remaining residue was dissolved in 10 mL of a 1: 1 mixed solution of methanol / triethylamine and then stirred at 0 ° C. for 1 hour. The solution was concentrated under reduced pressure. The remaining residue was then stirred in 15 mL of dichloromethane and then 5 mL of acetic acid saturated with chlorine was added. The solution was stirred at 0 ° C. for 30 minutes, then the solvent and unreacted chlorine were removed under reduced pressure. The remaining residue was dissolved in 5 ml of toluene and then toluene was evaporated under reduced pressure. The remaining residue was dissolved in 20 mL of THF and reacted with 1 mL of 40% aqueous methylamine solution at 0 ° C. for 2 hours. The reaction solution was concentrated under reduced pressure, and extracted with 30 mL of water and dichloromethane (30 mL × 3). The organic layer was washed with brine, and then concentrated under reduced pressure. The remaining residue was purified by column chromatography (hexane / ethyl acetate = 3: 2) to give solid 5- {3-chloro-4- (N-methylaminosulfonyl) phenyl} -2,2-dimethyl-4 -Phenyl-3 (2H62 mg of furanone were obtained. mp: 136-137oC. NMR: δ 1.58 (s, 6H), 2.66 (d,J =5.4 Hz, 3H), 4.94 (q,J =5.4 Hz, 1H), 7.28 (m, 2H), 7.39 (m, 3H), 7.63 (dd,J =8.4, 1.8 Hz, 1H), 7.84 (d,J =1.8 Hz, 1H), 8.03 (d,J =8.4 Hz, 1H). IR (cm-One): 3315, 1697, 1587, 1394, 1336, 1242, 1164.
    [1458] Example 373
    [1459] 5- {3-chloro-4- (N-ethylaminosulfonyl) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -Furanone
    [1460]
    [1461] The title compound was obtained by the method of Example 372, except that 70% aqueous ethylamine solution was used. mp: 72-73 o C. NMR: δ 1.11 (t, J = 7.2 Hz, 3H), 1.57 (s, 6H), 3.02 (m, 2H), 4.93 (t, J = 6.0 Hz, 1H), 7.28 (m, 2H), 7.39 (m, 3H), 7.62 (dd, J = 8.4, 1.8 Hz, 1H), 7.83 (d, J = 1.8 Hz, 1H), 8.03 (d, J = 8.1 Hz, 1H) . IR (cm -1 ): 3300, 1698, 1618, 1587, 1393, 1337, 1241, 1163.
    [1462] Example 374
    [1463] 5- [4-{(acetylamino) sulfonyl} -3-chlorophenyl] -2,2-dimethyl-4-phenyl-3 ( 2H ) -Furanone
    [1464]
    [1465] 150 mg of 5- {4- (aminosulfonyl) -3-chlorophenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone (Example 367) in 10 ml of dichloromethane was triethylamine In the presence of 0.5 ml and 15 mg of 4- (N, N-dimethylamino) pyridine, the reaction was reacted with 0.3 ml of acetic anhydride for 12 hours at room temperature. The reaction mixture was concentrated under reduced pressure, and extracted with 30 mL of water and dichloromethane (30 mL x 3). The organic layer was concentrated under reduced pressure, and then purified by column chromatography (hexane / ethyl acetate = 2: 1) to give a solid 5- [4-{(acetylamino) sulfonyl} -3-chlorophenyl] -2,2- 113 mg of dimethyl-4-phenyl-3 ( 2H ) -furanone were obtained. mp: 194-195 o C. NMR: δ 1.57 (s, 6H), 2.10 (s, 3H), 7.27 (m, 2H), 7.40 (m, 3H), 7.68 (dd, J = 8.4, 1.8 Hz, 1H), 7.85 (d, J = 1.5 Hz, 1H), 8.18 (d, J = 8.1 Hz, 1H), 8.45 (br s, 1H). IR (cm -1 ): 3195, 3104, 1698, 1377, 1164.
    [1466] Example 375
    [1467] 5- [3-chloro-4-{(propionylamino) sulfonyl} phenyl] -2,2-dimethyl-4-phenyl-3 ( 2H ) -Furanone
    [1468]
    [1469] 150 mg of 5- {4- (aminosulfonyl) -3-chlorophenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone (Example 367) were prepared in the same manner as in Example 374 In a similar manner, reaction with propionic anhydride yields 132 mg of 5- [3-chloro-4-{(propionylamino) sulfonyl} phenyl] -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone. Obtained. mp: 191-192 o C. NMR: δ 1.09 (t, J = 7.5 Hz, 3H), 1.57 (s, 6H), 2.32 (q = 7.5 Hz, 2H), 7.27 (m, 2H), 7.39 (m , 3H), 7.68 (dd, J = 8.4, 1.8 Hz, 1H), 7.84 (d, J = 1.5 Hz, 1H), 8.20 (d, J = 8.4 Hz, 1H), 8.37 (br s, 1H). IR (cm -1 ): 3204, 3105, 1699, 1458, 1396, 1164.
    [1470] Example 376
    [1471] 5- [4-{( n -Butyrylamino) sulfonyl} -3-chlorophenyl] -2,2-dimethyl-4-phenyl-3 ( 2H ) -Furanone
    [1472]
    [1473] 5- {4- (aminosulfonyl) -3-chlorophenyl} -2,2-dimethyl-4-phenyl-3 (2H) -Furanone (Example 367) 150 mg is reacted with butyric anhydride in a manner similar to that in Example 374 to give 5- [3-chloro-4-{(n-Butyrylamino) sulfonyl} phenyl] -2,2-dimethyl-4-phenyl-3 (2H124 mg of) -furanone were obtained. mp: 119-120oC. NMR: δ 0.89 (t,J =7.5 Hz, 3H), 1.57 (s, 6H), 1.59 (m, 2H), 2.27 (t,J =7.5 Hz, 2H), 7.28 (m, 2H), 7.40 (m, 3H), 7.69 (dd,J =8.4, 1.8 Hz, 1H), 7.83 (d,J =1.8 Hz, 1H), 8.20 (d,J =8.4 Hz, 1 H), 8.48 (br s, 1 H). IR (cm-One): 3191, 3105, 1698, 1684, 1453, 1242, 1187.
    [1474] Example 377
    [1475] 2,2-dimethyl-4- (3-fluorophenyl) -5- {3-methyl-4- (methylthio) phenyl} -3 ( 2H ) -Furanone
    [1476]
    [1477] After dissolving 437 mg of 1- {3-methyl-4- (methylthio) phenyl} -2- (3-fluorophenyl) -ethan-1-one in 50 ml of dry THF, 60% sodium hydride oil dispersion 67 mg was added and stirred at 0 ° C. for 1 hour, and 0.8 ml of α-bromoisobutyryl cyanide diluted with 25 ml of THF was added dropwise. The temperature of the reaction solution was slowly raised to room temperature and stirred overnight. The solvent was then removed under reduced pressure and the remaining residue was extracted with 50 mL of water and dichloromethane (50 mL × 3). The organic layer was concentrated under reduced pressure, and then purified by column chromatography (hexane / ethyl acetate = 6: 1) to give 2,2-dimethyl-4- (3-fluorophenyl) -5- {3-methyl-4- ( 312 mg of methylthio) phenyl} -3 ( 2H ) -furanone were obtained. NMR: δ 1.55 (s, 6H), 2.27 (s, 3H), 2.48 (s, 3H), 7.36 (m, 4H), 7.32 (m, 1H), 7.45 (m, 2H). IR (cm -1 ): 1694, 1601, 1385, 1260, 1192.
    [1478] Example 378
    [1479] 2,2-dimethyl-4- (3-fluorophenyl) -5- {3-methyl-4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [1480]
    [1481] 2,2-dimethyl-4- (3-fluorophenyl) -5- {3-methyl-4- (methylthio) phenyl} -3 ( 2H ) -furanone (Example 377) 257 mg of methylene chloride 50 After dissolving in mL, 170 mg of 70% m -chloroperoxybenzoic acid was added thereto, stirred at 0 ° C for 1 hour, and then 10 mL of 5% aqueous sodium bicarbonate solution was added thereto. The solution was further stirred for 10 minutes. The reaction mixture was concentrated under reduced pressure and extracted with 50 mL of water and dichloromethane (30 mL x 3). The organic layer was concentrated under reduced pressure, and purified by column chromatography (hexane / ethyl acetate = 2: 1) to give a solid 2,2-dimethyl-4- (3-fluorophenyl) -5- {3-methyl-4- 43 mg of (methylsulfonyl) phenyl} -3 ( 2H ) -furanone were obtained. mp: 138-139 ° C. NMR: δ 1.57 (s, 6H), 2.68 (s, 3H), 3.09 (s, 3H), 7.03 (m, 3H), 7.28 (m, 1H), 7.58 (dd, J = 8.4, 1.8 Hz, 1H), 7.63 (d, J = 1.2 Hz, 1H), 8.01 (d, J = 8.4 Hz, 1H). IR (cm −1 ): 1698, 1589, 1387, 1312, 1262. MS (FAB): 374 ( m + 1).
    [1482] Example 379
    [1483] 2,2-dimethyl-4- (3-fluorophenyl) -5- {3-methyl-4- (methylsulfinyl) phenyl} -3 ( 2H ) -Furanone
    [1484]
    [1485] As a side reaction in the synthesis of Example 378, 2,2-dimethyl-4- (3-fluorophenyl) -5- {3-methyl-4- (methylsulfinyl) phenyl} -3 (2H ) -Pew 219 mg of ranone was obtained. NMR: δ 1.56 (s, 6H), 2.32 (s, 3H), 2.70 (s, 3H), 7.04 (m, 3H), 7.31 (m, 1H), 7.49 (d, J = 0.9, 1H), 7.67 (dd, J = 8.1, 1.8 Hz, 1H), 7.94 (d, J = 8.4, 1H). IR (cm- 1 ): 1697, 1384, 1259, 1204, 1072.
    [1486] Example 380
    [1487] 5- {4- (aminosulfonyl) -3-methylphenyl} -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -Furanone
    [1488]
    [1489] In a manner similar to that used in Example 367, 2,2-dimethyl-4- (3-fluorophenyl) -5- {3-methyl-4- (methylsulfinyl) phenyl} -3 ( 2H )- Furanone (Example 379) 76 mg 5- {4- (aminosulfonyl) -3-methylphenyl} -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H )-from 201 mg Puranone was obtained. mp: 81-82 o C. NMR: δ 1.57 (s, 6H), 2.63 (s, 3H), 5.13 (br s, 2H), 7.03 (s, 3H), 7.27 (m, 1H), 7.45 (m , 1H), 7.61 (m, 1H), 7.96 (d, J = 8.4 Hz, 1H). IR (cm- 1 ): 3369, 3270, 1589, 1334, 1168. MS (FAB): 375 ( m + 1).
    [1490] Example 381
    [1491] 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-methyl-4- (methylthio) phenyl} -3 ( 2H ) -Furanone
    [1492]
    [1493] In a similar manner to the method in Example 377, 4-from 3-530 mg of 1- {3-methyl-4- (methylthio) phenyl} -2- (3,5-difluorophenyl) -ethan-1-one 357 mg (3,5-difluorophenyl) -2,2-dimethyl-5- {3-methyl-4- (methylthio) phenyl} -3 ( 2H ) -furanone were obtained. NMR: δ 1.55 (s, 6H), 2.29 (s, 3H), 2.50 (s, 3H), 6.74 (m, 1H), 6.89 (m, 2H), 7.08 (d, J = 8.1 Hz, 1H), 7.40 (dd, J = 8.4, 2.1 Hz, 1H), 7.45 (d, J = 1.5 Hz, 1H). IR (cm- 1 ): 1691, 1601, 1384, 1910, 1118.
    [1494] Example 382
    [1495] 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-methyl-4- (methylsulfonyl) phenyl} -3 ( 2H ) -Furanone
    [1496]
    [1497] 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-methyl-4- (methylthio) phenyl} -3 (2H) -Furanone (Example 381) 105 mg were dissolved in 50 ml of methanol, 30 ml of THF and 50 ml of water, followed by addition of 513 mg of oxone. The reaction mixture was stirred at rt for 4 h. After this time, the mixture was concentrated under reduced pressure and extracted with 50 mL of water and dichloromethane (30 mL x 3). The organic layer was concentrated under reduced pressure, followed by column chromatography (hexane / ethyl acetate = 3: 2) to give 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-methyl-4- (Methylsulfonyl) phenyl} -3 (2H97 mg of) -furanone were obtained. NMR: δ 1.57 (s, 6H), 2.71 (s, 3H), 3.05 (s, 3H), 6.82 (m, 1H), 7.12 (m, 1H), 7.59 (m, 1H), 7.63 (m, 1H ), 7.92 (m, 2 H).
    [1498] Example 383
    [1499] 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-methyl-4- (methylsulfinyl) phenyl} -3 (2H ) -Furanone
    [1500]
    [1501] 320 mg of 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-methyl-4- (methylthio) phenyl} -3 ( 2H ) -furanone (Example 381) After dissolving in 50 ml of dichloromethane, 172 mg of 70% m -chloroperoxybenzoic acid was added. The mixture was stirred at 0 ° C. for 1 hour and then 30 ml of 5% aqueous sodium bicarbonate solution was added. The solution was further stirred for 10 minutes. The mixture was then concentrated under reduced pressure and extracted with 50 mL of water and dichloromethane (30 mL x 3). The organic layer was concentrated under reduced pressure, purified by column chromatography (hexane / ethyl acetate = 1: 1), and 4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-methyl-4 211 mg of-(methylsulfinyl) phenyl} -3 ( 2H ) -furanone were obtained. NMR: δ 1.57 (s, 6H), 2.36 (s, 3H), 2.73 (s, 3H), 6.77 (m, 1H), 6.86 (m, 2H), 7.50 (m, 1H), 7.66 (m, 1H ), 7.99 (d, J = 8.4 Hz, 1H). IR (cm- 1 ): 1698, 1624, 1592, 1384, 1310, 1206, 1072, 915.
    [1502] Example 384
    [1503] 5- {4- (aminosulfonyl) -3-methylphenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -Furanone
    [1504]
    [1505] 4- (3,5-Difluorophenyl) -2,2-dimethyl-5- {3-methyl-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone from Example 367 from 240 mg A method similar to the one used was carried out to obtain 5- {4- (aminosulfonyl) -3-methylphenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H )- 33 mg of furanone was obtained. NMR: δ 1.56 (s, 6H), 2.66 (s, 3H), 4.98 (br s, 2H), 6.85 (m, 3H), 7.41 (m, 1H), 7.80 (m, 1H), 7.92 (m, 1H).
    [1506] Example 385
    [1507] 4- (3-chlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl}-( 2H ) -Furan-3-thione
    [1508]
    [1509] 4- (3-chlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furan-3-thione (Example 278) 130 mg Was dissolved in 20 ml of toluene and stirred under reflux for 12 hours in the presence of Lawson reagent 67 mg. The solvent was removed under reduced pressure, and the remaining residue was extracted with 50 mL of water and dichloromethane (50 mL × 3). The organic layer was concentrated under reduced pressure, purified by column chromatography (hexane / ethyl acetate = 4: 1), and the solid 4- (3-chlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- 117 mg of (methylsulfonyl) phenyl}-( 2H ) -furan-3-thione were obtained. mp: 105-106 o C. NMR: δ 1.71 (s, 6H), 3.24 (s, 3H), 7.12 (m, 3H), 7.41 (m, 1H), 7.52 (m, 2H), 7.92 (dd, J = 7.8, 7.2 Hz, 1H). IR (cm- 1 ): 1604, 1557, 1324, 1273, 1209, 1145, 1047, 963.
    [1510] Example 386
    [1511] 5- {4- (aminosulfonyl) -3-fluorophenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl- ( 2H ) -Furan-3-thione
    [1512]
    [1513] 5- {4- (aminosulfonyl) -3-fluorophenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone (Example 312) 140 5- {4- (aminosulfonyl) -3-fluorophenyl} -2,2-dimethyl-4- (3,5-difluoro) was run from mg using a method analogous to that used in Example 385 103 mg of phenyl)-( 2H ) -furan-3-thione was obtained. mp: 153 ~ 154 o C. NMR: δ 1.71 (s, 6H), 5.12 (br s, 2H), 6.84 (m, 3H), 7.48 (m, 2H), 7.90 (dd, J = 8.1, 8.1 Hz , 1H). IR (cm -1 ): 3416, 3279, 1624, 1557, 1356, 1273, 1173, 1121, 1064.
    [1514] Example 387
    [1515] 5- {2-chloro-4- (methylthio) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -Furanone
    [1516]
    [1517] 3.05 g of 1- {2-chloro-4- (methylthio) phenyl} -2-phenyl-ethan-1-one are dissolved in 60 mL of anhydrous THF and in the presence of 95% sodium hydride oil dispersion (1.0 g). After stirring for 20 minutes at 0 ° C., α-bromoisobutyryl cyanide (2.5 mL) diluted with 50 mL of THF was added dropwise. The temperature of the reaction solution was slowly raised to room temperature and then stirred overnight. The solvent was removed under reduced pressure, and extracted with 30 ml of water and diethyl ether (50 ml x 3). The organic layer was concentrated under reduced pressure, purified by column chromatography (hexane / ethyl acetate = 8: 1), and 5- {2-chloro-4- (methylthio) phenyl} -2,2-dimethyl-4-phenyl-3 2.73 g of ( 2H ) -furanone were obtained. NMR: δ 1.56 (s, 6H), 2.48 (s, 3H), 7.10 (dd, J = 8.4, 1.5 Hz, 1H), 7.24 (m, 3H), 7.26 (m, 3H), 7.37 (d, J = 1.5 Hz, 1H). IR (cm- 1 ): 1698, 1620, 1394, 1235, 1176, 1144.
    [1518] The compound of Example 388 was prepared in a similar manner to the method used in Example 387.
    [1519] Example 388
    [1520]
    [1521]
    [1522] Example 389
    [1523] 5- {2-chloro-4- (methylsulfonyl) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -Furanone
    [1524]
    [1525] 5- {2-chloro-4- (methylthio) phenyl} -2,2-dimethyl-4-phenyl-3 (2H) -Furanone (Example 387) After dissolving 350 mg in 75 ml of a mixed solution of methanol / THF / water 1: 1: 1, 1.0 g of oxone was added. The reaction mixture was stirred for 6 hours at room temperature and then concentrated under reduced pressure. The remaining residue was extracted with 25 mL of water and ethyl acetate (50 mL × 3). The organic layer was concentrated under reduced pressure, purified by column chromatography (hexane / ethyl acetate = 3: 1), and the solid 5- {2-chloro-4- (methylsulfonyl) phenyl} -2,2-dimethyl-4- Phenyl-3 (2H252 mg of furanone were obtained. mp: 89-90oC. NMR: δ 1.59 (s, 6H), 3.11 (s, 3H), 7.19 (m, 2H), 7.25 (m, 3H), 7.60 (d,J =8.1 Hz, 1H), 7.87 (dd,J =8.1, 1.8 Hz, 1H), 8.07 (d,J =1.8 Hz, 1H). IR (cm-One): 1701, 1625, 1586, 1391, 1319, 1153.
    [1526] The compound of Example 390 was prepared in a similar manner to the method in Example 389.
    [1527] Example 390
    [1528]
    [1529]
    [1530] Example 391
    [1531] 5- {2-chloro-4- (methylsulfinyl) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -Furanone
    [1532]
    [1533] 2.7 g of 5- {2-chloro-4- (methylthio) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone (Example 387) was dissolved in 80 ml of dichloromethane and stirred To the solution, 1.94 g of 70% m -chloroperoxybenzoic acid was added. The reaction mixture was stirred at 0 ° C. for 2 hours. Thereafter, 40 ml of 5% aqueous sodium bicarbonate solution was added to the solution, and the solution was stirred for 10 minutes. The solution was extracted with dichloromethane (50 mL x 3). The organic layer was concentrated under reduced pressure, purified by column chromatography (hexane / ethyl acetate = 1: 1), and the solid 5- {2-chloro-4- (methylsulfinyl) phenyl} -2,2-dimethyl-4- 978 mg of phenyl-3 ( 2H ) -furanone were obtained. mp: 135-136 o C. NMR: δ 1.59 (s, 6H), 2.78 (s, 3H), 7.22 (m, 3H), 7.25 (m, 2H), 7.54 (m, 2H), 7.79 (m, 1H). IR (cm- 1 ): 1698, 1623, 1392, 1242, 1145, 1063.
    [1534] The compound of Example 392 was synthesized in a similar manner to that in Example 391.
    [1535] Example 392
    [1536]
    [1537]
    [1538] Example 393
    [1539] 4- (3-chlorophenyl) -2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -Furanone
    [1540]
    [1541] 10.98 g of 4- (3-chlorophenyl) -2,2-dimethyl-5- {4- (methylthio) phenyl} -3 ( 2H ) -furanone (Example 168) was dissolved in 250 ml of dichloromethane and stirred To one solution, 6.59 g of 70% m -chloroperoxybenzoic acid was further added dropwise by diluting with 150 mL of dichloromethane. The reaction mixture was stirred at 0 ° C for 1 h. The reaction mixture was purified according to the method in Step 1 of Example 22, to obtain 4- (3-chlorophenyl) -2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -3 ( 2H )- 6.33 g of furanone were obtained. mp: 109-110 o C. NMR: δ 1.57 (s, 6H), 2.75 (s, 3H), 7.17 (m, 1H), 7.31 (m, 2H), 7.65 (d, J = 8.4 Hz, 2H) , 7.80 (d, J = 8.7 Hz, 2H).
    [1542] Biological assessment
    [1543] Activity evaluation of COX-2 and COX-1 in vitro [J. Pharmacol. Exp. Ther. 166, 96 (1996)]
    [1544] Collection of Mouse Peritoneal Macrophages
    [1545] The abdominal skin of C57BL / 6 mice was disinfected with 70% ethanol aqueous solution, and then the abdominal skin was removed while being careful not to damage the peritoneum. 5 ml of cold phosphate buffer (PBS) was injected into the abdominal cavity, and 1 minute later, the peritoneal solution containing the macrophages was collected using a syringe and a needle. The collected solution was centrifuged at 1500 rpm for 5 minutes to obtain cell pellets. The pellet was dispersed in RPMI-1640 medium containing 100 units / ml penicillin and 100 μg / ml screptomycin.
    [1546] COX-2 Activity Assessment
    [1547] In order to knock out the activity of the intracellular COX-1 enzyme, the dispersed pellets were treated with 500 μM of aspirin. The suspension was diluted in RPMI-1640 medium to contain 1 × 10 6 cells / ml. 100 μl of the suspension was added to each well of a 96-well ELISA plate. In order to attach the macrophages to the bottom of the plate, the plate was incubated for 2 hours at 37 ° C. and 5% CO 2 . Cells that did not adhere to the plate were removed by washing twice with PBS. Purity of the macrophages obtained therefrom was measured by differential counting. The RPMI-1640 medium containing 3% fetal bovine serum albumin was added to each well of the plate and stimulated with 10 μg / ml lipopolysaccharide (LPS). This procedure usually results in 5 × 10 5 cells / ml. Under conditions of 37 ° C., 5% CO 2, the LPS-treated suspension was incubated for 16 hours to induce COX-2. The medium was then removed and the macrophages washed twice with PBS. 130 μl of RPMI-1640 medium was added to each well, and the macrophage solution was incubated at 37 ° C. for 10 minutes, and then treated with 10 μM arachidonic acid and an appropriate amount of the compound of the present invention. After further incubating the plate for 10 minutes, the supernatant was collected using a micro pipette to measure the amount of PGE 2 in the solution. The amount of PGE 2 present in the collected solution was measured by known radio-immuno assay or known enzyme-immunoassay [Methods in Enzymol. 86 , 258 (1982); Methods in Enzymol. 187 , 24 (1990). Arachidonic acid 10 ㎍ / ㎖ and the PGE 2 quantity up to PGE 2 quantity generated by treating the produced without processing arachidonic acid PGE 2 quantity by the assumption that the smallest possible PGE 2 is the amount, COX by the compound of the invention The degree of inhibition of -2 was calculated.
    [1548] COX-1 activity assessment
    [1549] In evaluating COX-1 inhibitory activity by the compounds of the present invention, the same method used in the above COX-2 activity assessment was used except that the following two steps were omitted: 1) Gene Deficient COX-1 Activity Aspirin treatment, 2) LPS treatment for inducing COX-2.
    [1550] IC 50 data of COX-1 and COX-2 for selected compounds in the present invention are summarized in Table 1. IC 50 means the concentration of a compound when the COX-1 or COX-2 enzyme activity represents 50% of the activity without treatment of the compound. In order to determine the IC 50 values for the compounds of the present invention, enzyme activity was measured at various concentrations near the IC 50 values of the compounds. Usually, the IC 50 value for the compound of the present invention was calculated by measuring the enzyme activity at 4 to 5 concentrations.
    [1551] TABLE 1
    [1552]
    [1553]
    [1554]
    [1555] In vivo ( In vivo) Anti-inflammatory efficacy of
    [1556] Carrageenan-induced foot edema (CFE) in rats
    [1557] An appropriate amount of the compound of the present invention was suspended in 1% methyl cellulose (MC) solution and orally administered to Sprague-Dawley (SD) male rats weighing 150-200 g. The dose of excipient to the compound of the invention was adjusted to be below 10 ml / kg body weight of the animal. After 1 hour, 0.1 ml of 1% carrageenan saline solution was injected directly into the rat's right paw, causing edema in the paw. Using a displacement plethysmometer (Ugo Basile, Italy), the volume of the paw was measured immediately after the carrageenan injection and 3 hours after. Using the volume, the percent CFE inhibition according to the compound amount of the present invention was calculated according to the following formula. Br. J. Pharmacol. 41 , 132 (1971)]
    [1558] CFE inhibition% = (1- Δ treatment / Δ control) x100
    [1559] In the formula, Δ treatment group = [volume volume after 3 hours after carrageenan injection]-[volume immediately after carrageenan injection] for drug-treated rats, and [Delta] control group [after carrageenan injection for mice not treated with drug] Volume volume after 3 hours]-[volume volume immediately after kerageenin injection]
    [1560] CFE inhibition data for selected compounds in the present invention are summarized in Table 2 below. In order to determine the inhibitory activity of the compounds of the invention according to the dose, usually 5 to 8 animals were used for both the control and drug-administered groups.
    [1561] TABLE 2
    [1562]
    [1563] Evaluation of Anti-inflammatory Effects on Adjuvant Arthritis
    [1564] Arthritis was induced by injecting 1 mg of Mycobacterium butyricum into 0.1 ml Freund's adjuvant and subcutaneously injected into the base of the tail of a male SD rat weighing 180-200 g. . 14 days after the adjuvant injection, the volume of the paw was measured using a displacement volumetric apparatus. Animals with an increased volume of at least 0.37 ml above the normal volume (untreated with adjuvant) were selected and grouped randomly. From day 14 after the adjuvant injection to rats with randomly isolated arthritis, the compound of the present invention was orally suspended in a 1% aqueous methyl cellulose solution once daily to administer a predetermined daily dose. The compound was continuously administered until 22 days after the adjuvant injection, and the daily volume was measured using a replacement volumetric apparatus. The volumetric volume of 5-8 rats on day 22 was averaged, and the inhibition rate (%) of adjuvant arthritis (AA) by the compound of the present invention was measured according to the following formula.
    [1565] % Inhibition against AA = (1-Δ treatment / Δcontrol) × 100
    [1566] In the formula, Δ treatment group = [(volume volume on day 22) / (volume volume on day 14) -1] for drug-treated mice, and Δ control = [(volume volume on day 22) / (for mice not treated with drug). Volume of Day 14) -1]
    [1567] ED 50 data of selected compounds of the invention for adjuvant arthritis are summarized in Table 3 below. The ED 50 value for adjuvant means the daily dose of the compound when adjuvant arthritis is 50% inhibited. ED 50 values were determined from the dose-response curves for each compound.
    [1568] TABLE 3
    [1569]
    [1570] Pharmacokinetic Tests in Rats
    [1571] An appropriate amount of the compound suspended in an aqueous 1% methyl cellulose solution was orally administered to SD male rats, and blood samples were collected from the retro-orbital sinus at a predetermined time for 24 to 48 hours. Each blood sample was centrifuged to separate plasma and the plasma was stored at 4 ° C. until analysis. The plasma samples thus obtained were analyzed by reverse phase HPLC (high performance liquid chromatography) using appropriate internal standards.
    [1572] Figure 1 shows the pharmacokinetic test for Example 393 administered orally to SD rats. A significant amount of Example 62 was detected in plasma and it was confirmed that the sulfoxide group of Example 393 was converted in vivo to a sulfonyl group.
    [1573]
    [1574] Example 393 Example 62
    [1575] The sulfoxide compound of the present invention was itself a COX-2 inhibitor, but after being absorbed into the human body, it can be seen from the pharmacokinetic experiment results for Example 393 can be converted to the corresponding sulfone (Fig. 1). Therefore, the sulfoxide compounds of the present invention can be used as prodrugs of the corresponding sulfones.
    [1576] Analgesic effect test
    [1577] Acetic acid-induced riding test
    [1578] ICR mice weighing 18-22 g were placed under brightness control conditions (12 hours on / 12 hours off) and fasted overnight before analgesic effect testing. The compound of the present invention dissolved in a mixed solvent or excipient of ethanol / twin 80 / physiological saline 10:10:80 was orally administered to mice. The excipient dose administered was adjusted to 10 ml / kg body weight. After 1 hour, 0.2 ml of 1.2% acetic acid was administered to the animal by intraperitoneal injection. After 6 minutes, the number of abdominal contractions over 6 minutes was counted. Compared with the number of abdominal contractions seen in the placebo group, the analgesic effect was shown as a decrease in the number of abdominal contractions. Med. Chem. 39 , 4942 ( 1996 ). ED 50 in the mouse riding test means the dose when the abdominal contraction count is half that of the placebo group. Ten animals were used in each group in this test.
    [1579] Carrageenan-induced thermal hyperalgesia test
    [1580] SD male rats weighing 170-220 g were allowed to freely drink only water and fasted for at least 16 hours before the experiment. The compounds of the invention suspended in 20 ml of 0.5% methylcellulose / 0.025% Tween-20 or excipients were administered to mice. Thereafter, only 100 ml of 1% carrageenin or 100 ml of saline dissolved in physiological saline was injected locally to the left hind paw of each animal. After 3 hours, nociceptive responses to recessive stimuli were measured as follows: Prior to testing, rats were placed in a transparent plastic box with a glass plate bottom for 10 minutes to familiarize themselves with the test environment. In the control and drug treatment groups, the withdrawal latency was measured in seconds, and the inhibition rate was calculated to evaluate the analgesic effect of the compound [Pain 32 , 77 (1988)]. Six animals were used in each group in this study.
    [1581] Analgesic efficacy for the two compounds of the present invention are summarized together in comparison to indomethacin in Table 4 below.
    [1582] TABLE 4
    [1583]
    [1584] Gastrointestinal safety test
    [1585] The gastrointestinal safety of the compounds of the present invention was evaluated as follows. Otterness et al. , Laboratory Models for Testing Nonsteroidal Anti-inflammatory Drugs in Nonsteroidal Anti-inflammatory Drugs ; ed John Wiley & Sons pp 217-227 (1985); Wiley Interscience; New York]: The compound of the present invention suspended in an aqueous 1% methylcellulose solution was orally administered to SD male rats once daily for 7 days at a predetermined dose. Four hours after the last dose (day 7 of dosing), the stomach was removed and the stomach lining was visually observed. Gastrointestinal safety was assessed with the " Ulcer Index ", expressed as:
    [1586] 1 point: normal stomach
    [1587] 2-point: one or more pointed ulcers
    [1588] 3 points: 2 or less erosions with pointy ulcers (erosion is defined as ulcers greater than 1 mm)
    [1589] 4 points: 2 or more erosions accompanied by punctual ulcers
    [1590] 5 points: Erosion with bleeding
    [1591] To assess gastrointestinal safety for the compounds of the invention, usually eight animals were used. The ulcer index for the compound was calculated by averaging the ulcer index of each animal, and Table 5 below shows the gastrointestinal safety of some COX-2 selective inhibitors of the invention.
    [1592] TABLE 5
    [1593]
    [1594] The description of the invention disclosed above first shows preferred embodiments and examples thereof. It will be apparent to those skilled in the art that changes and modifications may be readily made in the practical application of the invention described herein without departing from the object and scope of the invention as set forth in the following claims.
    权利要求:
    Claims (25)
    [1" claim-type="Currently amended] A compound of formula (I) or a pharmaceutically acceptable salt thereof:

    (Ⅰ)
    In the formula,
    X is a halo, hydrido or alkyl group;
    Y is an alkylsulfonyl, aminosulfonyl, alkylsulfinyl, (N-acylamino) sulfonyl, (N-alkylamino) sulfonyl, or an alkylthio group;
    Z is oxygen or sulfur atom;
    R 1 and R 2 are each independently selected from lower alkyl groups, or are linked together to the 2nd position carbon of the 3 ( 2H ) -furanone ring to form a 4- to 6-membered aliphatic- or hetero-ring; And AR is an aromatic group consisting of 5 to 10 atoms which may be substituted or unsubstituted.
    [2" claim-type="Currently amended] The method of claim 1,
    X is selected from halo, hydrido and lower alkyl;
    Y is selected from (lower alkyl) sulfonyl, aminosulfonyl, (lower alkyl) sulfinyl, (lower N-acylamino) sulfonyl, (lower N-alkylamino) sulfonyl and (lower alkyl) thio;
    Z is selected from oxygen and sulfur atoms;
    R 1 and R 2 are independently selected from lower alkyl groups, or R 1 and R 2 are pentidedenyl (-CH 2 -CH) linked together to carbon 2 of the 3 ( 2H ) -furanone ring to form a ring; 2 -CH 2 -CH 2- ), hexylydenyl (-CH 2 -CH 2 -CH 2 -CH 2 -CH 2- ), 4-tetrahydro- (4H) -pyranylideneyl (-CH 2 -CH 2 -O-CH 2 -CH 2- ), 3-tetrahydrofuranylideneyl (-CH 2 -O-CH 2 -CH 2- ) or 3-oxetanylideneyl (-CH 2 -O-CH 2- ); And AR is an aromatic group consisting of substituted or unsubstituted 5 to 10 atoms, selected from aromatic groups encompassing the following groups, but not limited to these aromatic groups;

    Wherein R 3 to R 7 , when present, are respectively hydrido, halo, alkyl, haloalkyl, alkoxy, haloalkoxy, acyl, nitro, amino, N-alkylamino, N, N-dialkylamino, N-acyl Independently selected from amino, (haloacyl) amino, formyl, cyano, azido, hydroxy, alkylthio, alkylsulfonyl, phenyl, alkoxyalkyl and hydroxyalkyl, or adjacent two of R 3 to R 7 The groups are connected to each other to form methylenedioxy; And,
    R 8 to R 19 , when present, are each selected from hydrido, halo, alkyl, acyl, haloalkyl, alkoxy, formyl, cyano, nitro, amino, azido and acylamino, or a pharmaceutically acceptable Possible salts thereof.
    [3" claim-type="Currently amended] The method according to claim 1 or 2,
    X is selected from fluoro, chloro, bromo, hydrido, methyl, ethyl and n-propyl;
    Y is methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, aminosulfonyl, methylsulfinyl, ethylsulfinyl, n-propylsulfinyl, (N-acetylamino) sulfonyl, (N-propionylamino) Sulfonyl, (N-butyrylamino) sulfonyl, (N-methylamino) sulfonyl, (N-ethylamino) sulfonyl, methylthio, ethylthio and n-propylthio;
    Z is selected from oxygen and sulfur atoms;
    R 1 and R 2 are independently selected from methyl and ethyl, or R 1 and R 2 are linked to the carbon number 2 of the 3 ( 2H ) -furanone ring to form a ring, pentillydenyl (-CH 2 -CH 2 -CH 2 -CH 2- ), hexylideneyl (-CH 2 -CH 2 -CH 2 -CH 2 -CH 2- ), 4-tetrahydro- (4H) -pyranylidenyl (-CH 2 -CH 2 -O-CH 2 -CH 2- ), 3-tetrahydrofuranylideneyl (-CH 2 -O-CH 2 -CH 2- ) and 3-oxetanylideneyl (-CH 2 -O-CH 2- );
    R 3 to R 7 , when present, are respectively hydrido, fluoro, chloro, bromo, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, n-pentyl, isopentyl , Fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 1-fluoroethyl, 2,2-difluoroethyl, 1,2-difluoroethyl, 1,1-di Fluoroethyl, 2,2,2-trifluoroethyl, methoxy, ethoxy, n-propyloxy, isopropyloxy, n-butoxy, trifluoromethoxy, difluoromethoxy, fluoromethoxy, acetyl , Propionyl, n-butanoyl, isobutanoyl, n-pentanoyl, nitro, amino, N-methylamino, N-ethylamino, Nn-propylamino, N, N-dimethylamino, N-acetylamino, N Propionylamino, N- (trifluoroacetyl) amino, formyl, hydroxy, methylthio, ethylthio, n-propylthio, methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, phenyl, hydroxy Butyl, 1-hydroxyethyl, and 2-hydroxy-or independently selected from ethyl, or R 3 to R 7 are linked together the two groups adjacent to form a methylenedioxy; And R 8 to R 19 , when present, are respectively hydrido, fluoro, chloro, bromo, methyl, ethyl, n-propyl, isopropyl, acetyl, propionyl, methoxy, ethoxy, isopropyloxy, Compounds or pharmaceutically acceptable salts thereof, independently selected from n-propyloxy and formyl.
    [4" claim-type="Currently amended] A compound according to claim 1 or a pharmaceutically acceptable salt thereof:

    (Ⅱ)
    Food,
    Y is alkylsulfonyl, aminosulfonyl, alkylsulfinyl, (N-acylamino) sulfonyl, (N-alkylamino) sulfonyl or alkylthio;
    Z is oxygen or sulfur atom;
    R 1 and R 2 are independently selected from lower alkyl groups; And,
    R 3 to R 7 , when present, are respectively hydrido, halo, alkyl, haloalkyl, alkoxy, haloalkoxy, acyl, nitro, amino, N-alkylamino, N, N-dialkylamino, N-acylamino, Independently selected from N- (haloacyl) amino, formyl, cyano, azido, hydroxy, alkylthio, alkylsulfonyl, phenyl, alkoxyalkyl and hydroxyalkyl, or adjacent two of R 3 to R 7 The groups are connected to each other to form methylenedioxy.
    [5" claim-type="Currently amended] The method of claim 4, wherein
    Y is selected from (lower alkyl) sulfonyl, aminosulfonyl, (lower alkyl) sulfinyl, (lower N-acylamino) sulfonyl, (lower N-alkylamino) sulfonyl, and (lower alkyl) thio;
    Z is selected from oxygen and sulfur atoms;
    R 1 and R 2 are independently selected from methyl and ethyl groups; And,
    R 3 to R 7 , when present, are respectively hydrido, halo, lower alkyl, lower haloalkyl, lower alkoxy, lower haloalkoxy, lower acyl, nitro, amino, lower N-alkylamino, lower N, N-dialkyl Independently selected from amino, lower N-acylamino, (lower haloacyl) amino, formyl, cyano, azido, hydroxy, lower alkylthio, lower alkylsulfonyl, phenyl, lower alkoxyalkyl and lower hydroxyalkyl Or a pharmaceutically acceptable salt thereof, or two adjacent groups in R 3 to R 7 are linked to each other to form methylenedioxy.
    [6" claim-type="Currently amended] The method of claim 5,
    Y is methylsulfonyl, aminosulfonyl, methylsulfinyl, (N-acetylamino) sulfonyl, (N-propionylamino) sulfonyl, (N-butyrylamino) sulfonyl, (N-methylamino) sul Selected from among poly, (N-ethylamino) sulfonyl and methylthio;
    Z is selected from oxygen and sulfur atoms;
    R 1 and R 2 are independently selected from methyl and ethyl groups; And,
    R 3 to R 7 , when present, are respectively hydrido, fluoro, chloro, bromo, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, n-pentyl, isopentyl , Fluoromethyl, difluoromethyl, trifluoromethyl, 1-fluoroethyl, 2,2,2-trifluoroethyl, methoxy, trifluoromethoxy, difluoromethoxy, fluoromethoxy, acetyl , Propionyl, n-butanoyl, isobutanoyl, n-pentanoyl, nitro, amino, N, N-dimethylamino, N-acetylamino, N-propionylamino, formyl, hydroxy, methylthio, ethyl Independently selected from thio, n-propylthio, methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, phenyl, hydroxymethyl, 1-hydroxyethyl and 2-hydroxyethyl, or R 3 to R 7 A compound or a pharmaceutically acceptable salt thereof, wherein two adjacent groups in the group are linked to each other to form methylenedioxy.
    [7" claim-type="Currently amended] A compound according to claim 6, or a pharmaceutically acceptable salt thereof, selected from the following specific group of compounds:
    2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4-phenyl-3 ( 2H ) -furanone;
    2,2-dimethyl-4- (2-fluorophenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (3-fluorophenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (4-fluorophenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (3-fluoro-4-phenylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (2,4-difluorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (2,5-difluorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3,4-difluorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3,5-difluorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (2-chlorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3-chlorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (4-chlorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3-chloro-4-fluorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3-chloro-5-fluorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (4-chloro-3-fluorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (2,4-dichlorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3,4-dichlorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3,5-dichlorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (4-bromophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3-bromophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (2-methylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (3-methylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (4-methylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (4-ethylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (4-n-propylphenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (3-isopropylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (4-isopropylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (3-fluoro-4-isopropylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3-chloro-4-isopropylphenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (4-n-butylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (4-t-butylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (4-fluoro-2-methylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (5-fluoro-2-methylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (3-fluoro-4-methylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (2-methoxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (3-methoxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (4-methoxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (2-hydroxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (3-hydroxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (4-hydroxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (2,4-dimethoxyphenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3,4-dimethoxyphenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (3,4-methylenedioxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (3,5-dimethyl-4-methoxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (3,4-dimethylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (3-fluoro-4-methoxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (3-fluoro-4-hydroxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- {4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- {4- (ethylthio) phenyl} -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4,5-di- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- {4- (ethylsulfonyl) phenyl} -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- {3- (fluoromethyl) phenyl} -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- {4- (fluoromethyl) phenyl} -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- {3- (difluoromethyl) phenyl} -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- {4- (difluoromethyl) phenyl} -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- {2- (trifluoromethyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- {3- (trifluoromethyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- {3-fluoro-5- (trifluoromethyl) phenyl} -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- {3-chloro-5- (trifluoromethyl) phenyl} -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- {4-acetyl-3- (trifluoromethyl) phenyl} -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- {3-acetyl-5- (trifluoromethyl) phenyl} -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- {4- (trifluoromethyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- {3,5-di- (trifluoromethyl) phenyl} -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- {4-chloro-3- (trifluoromethyl) phenyl} -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (3-nitrophenyl) -3 ( 2H ) -furanone;
    4- (3-aminophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- {4- (N, N-dimethylamino) phenyl} -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (2-formylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (3-formylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (4-formylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- {3- (acetylamino) phenyl} -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3-acetylphenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (4-acetylphenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (4-biphenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- [4- (1-hydroxyethyl) phenyl] -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- [4- (1-hydroxymethyl) phenyl] -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -4-phenyl-3 ( 2H ) -furanone;
    2,2-dimethyl-4- (3-fluorophenyl) -5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (4-fluorophenyl) -5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (3,5-difluorophenyl) -5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    4- (3-chloro-4-fluorophenyl) -2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    4- (3-chloro-5-fluorophenyl) -2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    4- (3-chlorophenyl) -2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    4- (4-t-butylphenyl) -2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (2-fluorophenyl) -5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (3-fluorophenyl) -5- {4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {4- (methylthio) phenyl} -4-phenyl-3 ( 2H ) -furanone;
    4- (3-chlorophenyl) -2,2-dimethyl-5- {4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {4- (methylthio) phenyl} -4- {3- (trifluoromethyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -4- {3- (trifluoromethyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- {3-fluoro-5- (trifluoromethyl) phenyl} -5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    4- {3-chloro-5- (trifluoromethyl) phenyl} -2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    4- {3-acetyl-5- (trifluoromethyl) phenyl} -2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    4- {4-acetyl-3- (trifluoromethyl) phenyl} -2,2-dimethyl-5- {4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {4- (methylthio) phenyl} -4- (4-nitrophenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (4-methoxyphenyl) -5- {4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    4- (2,5-difluorophenyl) -2,2-dimethyl-5- {4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    4- (3,5-difluorophenyl) -2,2-dimethyl-5- {4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -4- (3-chloro-5-fluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -4- (3,4-dichlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -4- (3,5-dichlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {3- (trifluoromethyl) phenyl} -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {3-fluoro-5- (trifluoromethyl) phenyl} -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -4- {3-chloro-5- (trifluoromethyl) phenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    4- {3-acetyl-5- (trifluoromethyl) phenyl} -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 (2H) -furanone;
    4- {4-acetyl-5- (trifluoromethyl) phenyl} -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (3-methylphenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -4- (2,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (3,4-dimethylphenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -4- (2,4-dimethoxyphenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -4- (3,4-dimethoxyphenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    4- (3-acetylphenyl) -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    4- (3-acetyl-5-chlorophenyl) -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    4- (3-acetyl-4-chlorophenyl) -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    4- (3-acetyl-4-fluorophenyl) -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    4- (3-acetyl-5-fluorophenyl) -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -4- (3-chloro-4-fluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (3-methoxyphenyl) -3 ( 2H ) -furanone;
    4- (4-acetylphenyl) -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    4- (4-acetyl-3-chlorophenyl) -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    4- (4-acetyl-3-fluorophenyl) -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    4- (4-acetyl-3-bromophenyl) -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    4- {4- (acetylamino) phenyl} -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (2-methylphenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -4- (3,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (4-methylphenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {3,4- (methylenedioxy) phenyl} -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -4- (4-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (3-fluoro-4-phenylphenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -4- (4-bromophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (5-isopropyl-2-methoxyphenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (5-isopropylphenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {4- (ethylthio) phenyl} -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (2-methoxyphenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -4- (4-n-butylphenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -4- (3,5-dichlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (3,4,5-trimethoxyphenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (4-hydroxyphenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (4-fluoro-3-methoxyphenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (3,5-dimethyl-4-methoxyphenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (4-ethylphenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (3-phenylphenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (2-fluorophenyl) -3 ( 2H ) -furanone;
    4- (3-aminophenyl) -5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (3-nitrophenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (5-fluoro-2-methylphenyl) -3 ( 2H ) -furanone;
    2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4-phenyl-3 ( 2H ) -furanone;
    2-ethyl-4- (4-fluorophenyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-4- (3-fluorophenyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3-chlorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-4- (2-fluorophenyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (4-acetylphenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (4-acetyl-3-chlorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (4-acetyl-3-fluorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- {4-acetyl-3- (trifluoromethyl) phenyl} -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3,5-difluorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3,4-difluorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3-chloro-4-fluorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3-chloro-5-fluorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3,5-dichlorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-4- (4-methoxyphenyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-2-methyl-4- (4-methylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-2-methyl-4- (3-methylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    4- (3-acetylphenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3-acetyl-4-fluorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3-acetyl-4-chlorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- {3- (acetylamino) phenyl} -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-2-methyl-4- {3,4- (methylenedioxy) phenyl} -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- {4-Chloro-3- (trifluoromethyl) phenyl} -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- {5-chloro-3- (trifluoromethyl) phenyl} -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-4- {5-fluoro-3- (trifluoromethyl) phenyl} -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -fu Lanone;
    2-ethyl-4- (4-ethylphenyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-4- (3-methoxyphenyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-4- (3-isopropylphenyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-4- (4-isopropylphenyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-4- (3-fluoro-4-isopropylphenyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-4- (5-fluoro-4-isopropylphenyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3-chloro-4-isopropylphenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H) -furanone;
    4- (4-t-butylphenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- (4-n-propylphenyl) -3 ( 2H ) -furanone;
    4- (4-n-butylphenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3,4-dimethylphenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3,4-dichlorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3-aminophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- {3- (difluoromethyl) phenyl} -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-4- {4- (fluoromethyl) phenyl} -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (4-chlorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- {4- (trifluoromethyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- {4- (trifluoromethoxy) phenyl} -3 ( 2H ) -furanone;
    4- (4-chloro-3-fluorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-4- (4-fluoro-2-methylphenyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-4- (5-fluoro-2-methylphenyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3,4-dimethoxyphenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3,5-dimethoxyphenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-4- (5-fluoro-2-methylphenyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-4- (3-fluoro-4-methoxyphenyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3,5-difluorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3,5-dichlorophenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3,5-dimethyl-4-methoxyphenyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- (3,4,5-trimethoxyphenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-4-phenyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- (4-fluorophenyl) -2-methyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- (3-fluorophenyl) -2-methyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-4- (3-methylphenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -4- (3-chlorophenyl) -2-ethyl-2-methyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -4- (4-chlorophenyl) -2-ethyl-2-methyl-3 ( 2H ) -furanone;
    5- (4-aminosulfonylphenyl) -2-ethyl-2-methyl-4- {3- (trifluoromethyl) phenyl} -3 ( 2H ) -furanone;
    5- (4-aminosulfonylphenyl) -2-ethyl-2-methyl-4- {3-fluoro-5- (trifluoromethyl) phenyl} -3 ( 2H ) -furanone;
    5- (4-aminosulfonylphenyl)-{3-chloro-5- (trifluoromethyl) phenyl} -2-ethyl-2-methyl-4-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-4- {4- (trifluoromethyl) phenyl} -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -4- (3,5-difluorophenyl) -2-ethyl-2-methyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -4- (3,5-dichlorophenyl) -2-ethyl-2-methyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -4- (3,4-difluorophenyl) -2-ethyl-2-methyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- (3-methoxyphenyl) -2-methyl-3 ( 2H ) -furanone;
    4- (4-acetylphenyl) -5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-3 ( 2H ) -furanone;
    4- (4-acetyl-3-chlorophenyl) -5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-3 ( 2H ) -furanone;
    4- (4-acetyl-3-fluorophenyl) -5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-3 ( 2H ) -furanone;
    4- {4-acetyl-4- (trifluoromethyl) phenyl} -5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- (4-fluoro-3-methoxyphenyl) -2-methyl-3 ( 2H ) -furanone;
    2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -4-phenyl-3 ( 2H ) -furanone;
    2,2-diethyl-4- (3-fluorophenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3-chlorophenyl) -2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-diethyl-4- (3-methylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-diethyl-4- (3-methoxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -4- {3- (trifluoromethyl) phenyl} -3 ( 2H ) -furanone;
    2,2-diethyl-4- {3-fluoro-5- (trifluoromethyl) phenyl} -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- {3-chloro-5- (trifluoromethyl) phenyl} -2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-diethyl-4- (4-fluorophenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (4-chlorophenyl) -2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-diethyl-4- (4-methylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-diethyl-4- (4-methoxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -4- {4- (trifluoromethyl) phenyl} -3 ( 2H ) -furanone;
    4- (4-acetyl-3-chlorophenyl) -2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (4-acetylphenyl) -2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (4-acetyl-3-fluorophenyl) -2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (4-acetyl-2-chlorophenyl) -2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (4-acetyl-2-fluorophenyl) -2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-diethyl-4- (3,4-difluorophenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-diethyl-4- (3,5-difluorophenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-diethyl-4- (2,5-difluorophenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3-chloro-5-fluorophenyl) -2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-diethyl-4- (3,4-dimethoxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -4- (4-n-propylphenyl) -3 ( 2H ) -furanone;
    2,2-diethyl-4- (2,4-difluorophenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (4-t-butylphenyl) -2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-diethyl-4- (3,4-dimethylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-diethyl-4- (4-isopropylphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3-acetylphenyl) -2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3-chloro-4-fluorophenyl) -2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-diethyl-4- (3-fluoro-4-methoxyphenyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (3-chloro-4-fluorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl}-( 2H ) -furan-3-thione;
    2,2-dimethyl-4- (4-fluorophenyl) -5- {4- (methylsulfonyl) phenyl}-( 2H ) -furan-3-thione;
    2,2-dimethyl-4- (3-fluorophenyl) -5- {4- (methylsulfonyl) phenyl}-( 2H ) -furan-3-thione;
    4- (3,5-difluorophenyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl}-( 2H ) -furan-3-thione;
    5- [4-{(acetylamino) sulfonyl} phenyl] -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    5- [4-{(butyrylamino) sulfonyl} phenyl] -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- [4-{(N-methylamino) sulfonyl} phenyl] -4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- [4-{(N-ethylamino) sulfonyl} phenyl] -4- (3-fluorophenyl) -3 ( 2H ) -furanone.
    [8" claim-type="Currently amended] A compound according to claim 1 or a pharmaceutically acceptable salt thereof:

    (Ⅲ)
    Food,
    Y is N-alkylsulfonyl, aminosulfonyl, alkylsulfinyl, (N-acylamino) sulfonyl, (N-alkylamino) sulfonyl or alkylthio;
    Z is oxygen or sulfur atom;
    m and n are integers of 1 to 3 and satisfy the condition (m + n) < 4;
    P is selected from an oxygen atom and a methylene group (-CH 2- ); And,
    R 3 to R 7 , when present, are respectively hydrido, halo, alkyl, haloalkyl, alkoxy, haloalkoxy, acyl, nitro, amino, N-alkylamino, N, N-dialkylamino, N-acylamino, Independently selected from N- (haloacyl) amino, formyl, cyano, azido, hydroxy, alkylthio, alkylsulfonyl, phenyl, alkoxyalkyl and hydroxyalkyl, or adjacent two of R 3 to R 7 The groups are connected to each other to form methylenedioxy.
    [9" claim-type="Currently amended] The method of claim 8,
    Y is selected from (lower alkyl) sulfonyl, aminosulfonyl, (lower alkyl) sulfinyl, (lower N-acylamino) sulfonyl, (lower N-alkylamino) sulfonyl and (lower alkyl) thio;
    Z is selected from oxygen and sulfur atoms;
    m and n are integers of 1 to 3 and satisfy the condition (m + n) < 4;
    P is selected from an oxygen atom and a methylene group (-CH 2- ); And,
    R 3 to R 7 , when present, are respectively hydrido, halo, alkyl, haloalkyl, alkoxy, haloalkoxy, acyl, nitro, amino, N-alkylamino, N, N-dialkylamino, N-acylamino, Independently selected from N- (haloacyl) amino, formyl, cyano, azido, hydroxy, alkylthio, alkylsulfonyl, phenyl, lower alkoxyalkyl and lower hydroxyalkyl, or in R 3 to R 7 A compound or a pharmaceutically acceptable salt thereof, wherein two adjacent groups are linked to each other to form methylenedioxy.
    [10" claim-type="Currently amended] The method of claim 9,
    Y is methylsulfonyl, aminosulfonyl, methylsulfinyl, (N-acetylamino) sulfonyl, (N-propionylamino) sulfonyl, (N-butyrylamino) sulfonyl, (N-methylamino) sul Is selected from among poly, (N-ethylamino) sulfonyl and methylthio;
    Z is selected from oxygen and sulfur atoms;
    m and n are integers of 1 to 3 and satisfy the condition (m + n) < 4;
    P is an oxygen atom or a methylene group (-CH 2- ); And,
    R 3 to R 7 , when present, are independent from hydrido, fluoro, chloro, bromo, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, acetyl and propionyl, respectively Or a pharmaceutically acceptable salt thereof.
    [11" claim-type="Currently amended] A compound according to claim 10, or a pharmaceutically acceptable salt thereof, selected from the following group of compounds:
    2- {4- (methylsulfonyl) phenyl} -3-phenyl-1-oxa-spiro [4,4] non-2-en-4-one;
    3- (3-methylphenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one;
    3- (4-isopropylphenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one;
    3- (3,5-difluorophenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one;
    3- (2-fluorophenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one;
    3- (3-fluorophenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one;
    3- (3-chlorophenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one;
    3- (4-fluorophenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one;
    3- (4-acetylphenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one;
    3- (4-acetyl-3-fluorophenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one;
    3- (4-acetyl-3-chlorophenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,4] non-2-en-4-one;
    2- {4- (methylsulfonyl) phenyl} -3-phenyl-1-oxa-spiro [4,5] dec-2-en-4-one;
    2- {4- (methylsulfonyl) phenyl} -3- {3- (trifluoromethyl) phenyl} -1-oxa-spiro [4,5] dec-2-en-4-one;
    3- (3-methylphenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,5] dec-2-en-4-one;
    3- (4-acetylphenyl) -2- {4- (methylsulfonyl) phenyl} -1-oxa-spiro [4,5] dec-2-en-4-one;
    3- (3-fluorophenyl) -2- {4- (methylsulfonyl) phenyl} -1,8-dioxa-spiro [4,5] dec-2-en-4-one;
    3- (3,5-difluorophenyl) -2- {4- (methylsulfonyl) phenyl} -1,8-dioxa-spiro [4,5] dec-2-en-4-one;
    3- (3-chlorophenyl) -2- {4- (methylsulfonyl) phenyl} -1,8-dioxa-spiro [4,5] dec-2-en-4-one;
    3- (4-acetylphenyl) -2- {4- (methylsulfonyl) phenyl} -1,8-dioxa-spiro [4,5] dec-2-en-4-one;
    2- {4- (methylsulfonyl) phenyl} -3-phenyl-1,8-dioxa-spiro [4,5] dec-2-en-4-one;
    3- (3-chlorophenyl) -2- {4- (methylsulfonyl) phenyl} -1,8-dioxa-spiro [4,5] dec-2-en-4-one.
    [12" claim-type="Currently amended] The compound of formula (IV) or a pharmaceutically acceptable salt thereof:

    (Ⅳ)
    Food,
    X is halo or alkyl;
    Y is alkylsulfonyl, aminosulfonyl, alkylsulfinyl, (N-acylamino) sulfonyl, (N-alkylamino) sulfonyl or alkylthio;
    Z is oxygen or sulfur atom; And,
    R 3 to R 7 , when present, are each independently selected from hydrido, halo, alkyl, haloalkyl, alkyloxy, nitro, amino, N-acylamino, acyl, formyl, hydroxyalkyl, phenyl and cyano Or two adjacent groups in R 3 to R 7 are connected to each other to form methylenedioxy.
    [13" claim-type="Currently amended] The method of claim 12,
    X is halo or lower alkyl;
    Y is selected from (lower alkyl) sulfonyl, aminosulfonyl, (lower alkyl) sulfinyl, (lower N-acylamino) sulfonyl, (lower N-alkylamino) sulfonyl and (lower alkyl) thio;
    Z is selected from oxygen and sulfur atoms; And,
    R 3 to R 7 , when present, are independently selected from hydrido, halo, lower alkyl, lower haloalkyl, lower alkyloxy, nitro, amino and N- (lower acyl) amino, respectively, or a pharmaceutically acceptable Possible salts thereof.
    [14" claim-type="Currently amended] The method of claim 13,
    X is fluoro, chloro, bromo or methyl;
    Y is methylsulfonyl, ethylsulfonyl, aminosulfonyl, methylsulfinyl, ethylsulfinyl, (N-acetylamino) sulfonyl, (N-propionylamino) sulfonyl, (N-butyrylamino) sulfonyl , (N-methylamino) sulfonyl, (N-ethylamino) sulfonyl, methylthio and ethylthio;
    Z is selected from oxygen and sulfur atoms; And R 3 to R 7 , when present, are respectively hydrido, fluoro, chloro, bromo, methyl, ethyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy , n-propyloxy, isopropyloxy, n-butoxy, nitro, amino, N-acetylamino and N-propionylamino, compounds or pharmaceutically acceptable salts thereof.
    [15" claim-type="Currently amended] The compound according to claim 14, or a pharmaceutically acceptable salt thereof, selected from the group of compounds
    2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -4-phenyl-3 ( 2H ) -furanone;
    2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -4-phenyl-3 ( 2H ) -furanone;
    2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -4-phenyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-fluorophenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    4- (2-chlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    4- (2-chlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    4- (2-chlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-fluorophenyl} -4- (2-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    4- (3-chlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    4- (3-chlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    4- (3-chlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-fluorophenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    4- (4-chlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    4- (4-chlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    4- (4-chlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-fluorophenyl} -4- (4-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    4- (3,4-dichlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    4- (3,4-dichlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    4- (3,4-dichlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-fluorophenyl} -4- (3,4-dichlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -4- (2-fluorophenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -4- (2-fluorophenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -4- (2-fluorophenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-fluorophenyl} -2,2-dimethyl-4- (2-fluorophenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-fluorophenyl} -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-fluorophenyl} -2,2-dimethyl-4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    4- (2,4-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    4- (2,4-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    4- (2,4-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-fluorophenyl} -4- (2,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    4- (2,5-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    4- (2,5-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    4- (2,5-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-fluorophenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    4- (2,6-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    4- (2,6-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    4- (2,6-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-fluorophenyl} -4- (2,6-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    4- (3,4-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    4- (3,4-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    4- (3,4-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-fluorophenyl} -4- (3,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-fluorophenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -4- (2-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -4- (2-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -4- (2-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-fluorophenyl} -2,2-dimethyl-4- (2-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-fluorophenyl} -2,2-dimethyl-4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -4- (4-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -4- (4-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -4- (4-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-fluorophenyl} -2,2-dimethyl-4- (4-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -4- (4-nitrophenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -4- (4-nitrophenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -4- (4-nitrophenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-fluorophenyl} -2,2-dimethyl-4- (4-nitrophenyl) -3 ( 2H ) -furanone;
    4- (4-aminophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    4- (4-aminophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    4- (4-aminophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (4-aminophenyl) -5- {4- (aminosulfonyl) -3-fluorophenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    4- {4- (acetylamino) phenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    4- {4- (acetylamino) phenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    4- {4- (acetylamino) phenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- {4- (acetylamino) phenyl) -5- {4- (aminosulfonyl) -3-fluorophenyl} -2,2-dimethyl-3 ( 2H ) -furanone;
    4- (3-chlorophenyl) -5- {3-fluoro-4- (methylthio) phenyl} -4- (3-methoxyphenyl) -3 ( 2H ) -furanone;
    4- (3-chlorophenyl) -5- {3-fluoro-4- (methylsulfonyl) phenyl} -4- (3-methoxyphenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {2-fluoro-4- (methylthio) phenyl} -4-phenyl-3 ( 2H ) -furanone;
    2,2-dimethyl-5- {2-fluoro-4- (methylsulfinyl) phenyl} -4-phenyl-3 ( 2H ) -furanone;
    2,2-dimethyl-5- {2-fluoro-4- (methylsulfonyl) phenyl} -4-phenyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -2-fluorophenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    4- (2-chlorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    4- (2-chlorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    4- (2-chlorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -2-fluorophenyl} -4- (2-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    4- (3-chlorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    4- (3-chlorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    4- (3-chlorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -2-fluorophenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    2,2-dimethyl-5- {2-fluoro-4- (methylthio) phenyl} -4- (2-fluorophenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {2-fluoro-4- (methylsulfinyl) phenyl} -4- (2-fluorophenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {2-fluoro-4- (methylsulfonyl) phenyl} -4- (2-fluorophenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -2-fluorophenyl} -2,2-dimethyl-4- (2-fluorophenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {2-fluoro-4- (methylthio) phenyl} -4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {2-fluoro-4- (methylsulfinyl) phenyl} -4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {2-fluoro-4- (methylsulfonyl) phenyl} -4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -2-fluorophenyl} -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {2-fluoro-4- (methylthio) phenyl} -4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {2-fluoro-4- (methylsulfinyl) phenyl} -4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {2-fluoro-4- (methylsulfonyl) phenyl} -4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -2-fluorophenyl} -2,2-dimethyl-4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    4- (2,4-difluorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    4- (2,4-difluorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    4- (2,4-difluorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -2-fluorophenyl} -4- (2,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    4- (2,5-difluorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    4- (2,5-difluorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    4- (2,5-difluorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -2-fluorophenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    4- (3,4-difluorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    4- (3,4-difluorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    4- (3,4-difluorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -2-fluorophenyl} -4- (3,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    4- (3,5-difluorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    4- (3,5-difluorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    4- (3,5-difluorophenyl) -2,2-dimethyl-5- {2-fluoro-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -2-fluorophenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    2,2-dimethyl-5- {2-fluoro-4- (methylthio) phenyl} -4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {2-fluoro-4- (methylsulfinyl) phenyl} -4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {2-fluoro-4- (methylsulfonyl) phenyl} -4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -2-fluorophenyl} -2,2-dimethyl-4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    5- {3-bromo-4- (methylthio) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    5- {3-bromo-4- (methylsulfonyl) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    5- {3-bromo-4- (methylsulfinyl) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-bromophenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    5- {3-bromo-4- (methylthio) phenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-bromo-4- (methylsulfonyl) phenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-bromo-4- (methylsulfinyl) phenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-bromophenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-bromo-4- (methylthio) phenyl} -4- (4-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-bromo-4- (methylsulfonyl) phenyl} -4- (4-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-bromo-4- (methylsulfinyl) phenyl} -4- (4-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-bromophenyl} -4- (4-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-bromo-4- (methylthio) phenyl} -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    5- {3-bromo-4- (methylsulfonyl) phenyl} -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    5- {3-bromo-4- (methylsulfinyl) phenyl} -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-bromophenyl} -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    5- {3-bromo-4- (methylthio) phenyl} -2,2-dimethyl-4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    5- {3-bromo-4- (methylsulfonyl) phenyl} -2,2-dimethyl-4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    5- {3-bromo-4- (methylsulfinyl) phenyl} -2,2-dimethyl-4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-bromophenyl} -2,2-dimethyl-4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    5- {3-bromo-4- (methylthio) phenyl} -4- (2,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-bromo-4- (methylsulfonyl) phenyl} -4- (2,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-bromo-4- (methylsulfinyl) phenyl} -4- (2,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-bromophenyl} -4- (2,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-bromo-4- (methylthio) phenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-bromo-4- (methylsulfonyl) phenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-bromo-4- (methylsulfinyl) phenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-bromophenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-bromo-4- (methylthio) phenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-bromo-4- (methylsulfonyl) phenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-bromo-4- (methylsulfinyl) phenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-bromophenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-bromo-4- (methylthio) phenyl} -2,2-dimethyl-4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    5- {3-bromo-4- (methylsulfonyl) phenyl} -2,2-dimethyl-4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    5- {3-bromo-4- (methylsulfinyl) phenyl} -2,2-dimethyl-4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-bromophenyl} -2,2-dimethyl-4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylthio) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylsulfonyl) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylsulfinyl) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-chlorophenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylthio) phenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylsulfonyl) phenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylsulfinyl) phenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-chlorophenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylthio) phenyl} -4- (4-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylsulfonyl) phenyl} -4- (4-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylsulfinyl) phenyl} -4- (4-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-chlorophenyl} -4- (4-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylthio) phenyl} -4- (3-fluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylsulfonyl) phenyl} -4- (3-fluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylsulfinyl) phenyl} -4- (3-fluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-chlorophenyl} -4- (3-fluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylthio) phenyl} -4- (4-fluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylsulfonyl) phenyl} -4- (4-fluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylsulfinyl) phenyl} -4- (4-fluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-chlorophenyl} -4- (4-fluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylthio) phenyl} -4- (2,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylsulfonyl) phenyl} -4- (2,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylsulfinyl) phenyl} -4- (2,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-chlorophenyl} -4- (2,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylthio) phenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylsulfonyl) phenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylsulfinyl) phenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-chlorophenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylthio) phenyl} -4- (3,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylsulfonyl) phenyl} -4- (3,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylsulfinyl) phenyl} -4- (3,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-chlorophenyl} -4- (3,4-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylthio) phenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylsulfonyl) phenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylsulfinyl) phenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-chlorophenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-methyl-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-methyl-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-methyl-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-methylphenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylthio) phenyl} -2,2-dimethyl-4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylsulfonyl) phenyl} -2,2-dimethyl-4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    5- {3-chloro-4- (methylsulfinyl) phenyl} -2,2-dimethyl-4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-chlorophenyl} -2,2-dimethyl-4- (3-trifluoromethylphenyl) -3 ( 2H ) -furanone;
    5- {2-chloro-4- (methylthio) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    5- {2-chloro-4- (methylsulfinyl) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    5- {2-chloro-4- (methylsulfonyl) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -2-chlorophenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    5- {2-chloro-4- (methylthio) phenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {2-chloro-4- (methylsulfonyl) phenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {2-chloro-4- (methylsulfinyl) phenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -2-chlorophenyl} -4- (3-chlorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {2-chloro-4- (methylthio) phenyl} -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    5- {2-chloro-4- (methylsulfinyl) phenyl} -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    5- {2-chloro-4- (methylsulfonyl) phenyl} -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -2-chlorophenyl} -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    5- {2-chloro-4- (methylthio) phenyl} -2,2-dimethyl-4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    5- {2-chloro-4- (methylsulfinyl) phenyl} -2,2-dimethyl-4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    5- {2-chloro-4- (methylsulfonyl) phenyl} -2,2-dimethyl-4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -2-chlorophenyl} -2,2-dimethyl-4- (4-fluorophenyl) -3 ( 2H ) -furanone;
    5- {2-chloro-4- (methylthio) phenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {2-chloro-4- (methylsulfonyl) phenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {2-chloro-4- (methylsulfinyl) phenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -2-chlorophenyl} -4- (2,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {2-chloro-4- (methylthio) phenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {2-chloro-4- (methylsulfonyl) phenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {2-chloro-4- (methylsulfinyl) phenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -2-chlorophenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    2,2-dimethyl-5- {3-methyl-4- (methylthio) phenyl} -4-phenyl-3 ( 2H ) -furanone;
    2,2-dimethyl-5- {3-methyl-4- (methylsulfinyl) phenyl} -4-phenyl-3 ( 2H ) -furanone;
    2,2-dimethyl-5- {3-methyl-4- (methylsulfonyl) phenyl} -4-phenyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-methylphenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    2,2-dimethyl-4- (3-fluorophenyl) -5- {3-methyl-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (3-fluorophenyl) -5- {3-methyl-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (3-fluorophenyl) -5- {3-methyl-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-methylphenyl} -2,2-dimethyl-4- (3-fluorophenyl) -3 ( 2H ) -furanone;
    4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-methyl-4- (methylthio) phenyl} -3 ( 2H ) -furanone;
    4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-methyl-4- (methylsulfinyl) phenyl} -3 ( 2H ) -furanone;
    4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-methyl-4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) -3-methylphenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (N-methylaminosulfonyl) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    5- {3-chloro-4- (N-ethylaminosulfonyl) phenyl} -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    5- [4-{(acetylamino) sulfonyl} -3-chlorophenyl] -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    5- [3-chloro-4-{(Nn-propionylamino) sulfonyl} phenyl] -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    5- [3-chloro-4-{(Nn-butyrylamino) sulfonyl} phenyl] -2,2-dimethyl-4-phenyl-3 ( 2H ) -furanone;
    4- (3-chlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylthio) phenyl}-( 2H ) -furan-3-thione;
    4- (3-chlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfonyl) phenyl}-( 2H ) -furan-3-thione;
    4- (3-chlorophenyl) -2,2-dimethyl-5- {3-fluoro-4- (methylsulfinyl) phenyl}-( 2H ) -furan-3-thione;
    5- {4- (aminosulfonyl) -3-fluorophenyl} -4- (3-chlorophenyl) -2,2-dimethyl- ( 2H ) -furan-3-thione;
    4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-fluoro- (4-methylthio) phenyl}-( 2H ) -furan-3-thione;
    4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-fluoro- (4-methylsulfonyl) phenyl}-( 2H ) -furan-3-thione;
    4- (3,5-difluorophenyl) -2,2-dimethyl-5- {3-fluoro- (4-methylsulfinyl) phenyl}-( 2H ) -furan-3-thione;
    5-{(4-aminosulfonyl) -3-fluorophenyl} -4- (3,5-difluorophenyl) -2,2-dimethyl- ( 2H ) -furan-3-thione.
    [16" claim-type="Currently amended] A compound of formula (V) or a pharmaceutically acceptable salt thereof:

    (Ⅴ)
    Food,
    Y is alkylsulfonyl, aminosulfonyl, alkylsulfinyl, (N-acylamino) sulfonyl, (N-alkylamino) sulfonyl, or alkylthio;
    Z is oxygen or sulfur atom;
    R 1 and R 2 are independently selected from methyl and ethyl groups; And,
    AR is an aromatic group consisting of 5 to 10 substituted or unsubstituted atoms, with the exception of substituted or unsubstituted phenyl groups.
    [17" claim-type="Currently amended] The method of claim 16,
    Y is selected from (lower alkyl) sulfonyl, aminosulfonyl and (lower N-acylamino) sulfonyl;
    Z is selected from oxygen and sulfur atoms;
    R 1 and R 2 are independently selected from methyl and ethyl groups; And,
    AR is selected from the following specific aromatic groups:

    Wherein R 8 to R 19 , when present, are each selected from hydrido, halo, lower alkyl, lower acyl, lower haloalkyl, lower alkoxy, formyl, cyano, nitro, amino, azido and N-acylamino Compound, or a pharmaceutically acceptable salt thereof.
    [18" claim-type="Currently amended] The method of claim 17,
    Y is selected from methylsulfonyl, ethylsulfonyl, aminosulfonyl, (N-acetylamino) sulfonyl and (N-propionylamino) sulfonyl;
    Z is selected from oxygen and sulfur atoms;
    R 1 and R 2 are independently selected from methyl and ethyl groups; And,
    R 8 to R 19 in the presence of hydrido, fluoro, chloro, bromo, methyl, ethyl, isopropyl, acetyl, n-propionyl, trifluoromethyl, methoxy, ethoxy and formyl, respectively Selected, compounds or pharmaceutically acceptable salts thereof.
    [19" claim-type="Currently amended] 19. A compound according to claim 18 or a pharmaceutically acceptable salt thereof, selected from the following group of compounds:
    2,2-dimethyl-5- {4- (methylthio) phenyl} -4- (3-thienyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-4- {2- (3-methylthienyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- {2- (5-formylthienyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (2-benzo [b] thienyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (1-naphthyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (3-pyridyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (2-pyridyl) -3 ( 2H ) -furanone;
    4- (2-benzo [b] furanyl) -2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (2-naphthyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-4- {5- (2-fluorothienyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- {5- (3-fluorothienyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- {4- (2-fluorothienyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (2-thienyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (3-thienyl) -3 ( 2H ) -furanone;
    4- {2- (5-acetylthienyl)}-2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (2-furanyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- (3-furanyl) -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- {5- (3-fluorofuranyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- {5- (2-fluorofuranyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- {4- (2-fluorofuranyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- {4- (1-N-methylpyrazolyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- {4- (1-N-ethylpyrazolyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (4-pyridyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-4- {3- (6-methoxypyridyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- {4- (1-N-isopropylpyrazolyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (5-pyrimidinyl) -3 ( 2H ) -furanone;
    2,2-dimethyl-4- {3- (6-methylpyridyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- {2- (5-formyl-4-methylthienyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-4- [2- {5- (1,3-dioxolane) -2-yl} thienyl] -5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -fu Lanone;
    4- {2- (5-bromothienyl)}-2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2,2-dimethyl-5- {4- (methylsulfonyl) phenyl} -4- (4-pyrazolyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-4- (2-pyridyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-4- (3-pyridyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-4- (4-pyridyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-4- {4- (1-N-methylpyrazolyl)}-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- {4- (1-N-ethylpyrazolyl)}-2-methyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-4- {4- (1-N-isopropylpyrazolyl)}-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2-ethyl-2-methyl-4- (3-thienyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- {4- (2-fluorothienyl)}-2-methyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- {5- (2-fluorothienyl)}-2-methyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- {5- (3-fluorothienyl)}-2-methyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- (2-furanyl) -2-methyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- (3-furanyl) -2-methyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- {5- (3-fluorofuranyl)}-2-methyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- {4- (2-fluorofuranyl)}-2-methyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2-ethyl-4- {5- (2-fluorofuranyl)}-2-methyl-3 ( 2H ) -furanone;
    2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -4- (3-thienyl) -3 ( 2H ) -furanone;
    2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -4- (2-thienyl) -3 ( 2H ) -furanone;
    2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -4- (2-pyridyl) -3 ( 2H ) -furanone;
    2,2-diethyl-5- {4- (methylsulfonyl) phenyl} -4- (4-pyridyl) -3 ( 2H ) -furanone;
    2,2-diethyl-4- {4- (1-N-methylpyrazolyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- (3-pyridyl) -3 ( 2H ) -furanone;
    2-ethyl-2-methyl-4- {4- (1-N-methylpyrazolyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- (4-pyrazolyl) -3 ( 2H ) -furanone;
    2-ethyl-4- {4- (1-N-ethylpyrazolyl)}-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- {4- (1-N-isopropylpyrazolyl)}-3 ( 2H ) -furanone;
    2-ethyl-2-methyl-4- {3- (6-methoxypyridyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-2-methyl-4- {3- (6-methylpyridyl)}-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- (3-thienyl) -3 ( 2H ) -furanone;
    2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- {4- (2-fluorothienyl)}-3 ( 2H ) -furanone;
    2-ethyl-4- (2-furanyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-4- (3-furanyl) -2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-4- {5- (3-fluorofuranyl)}-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-4- {5- (2-fluorofuranyl)}-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-4- {4- (2-fluorofuranyl)}-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (2-benzo [b] thienyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- (2-benzo [b] furanyl) -2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- (2-thienyl) -3 ( 2H ) -furanone;
    2-ethyl-4- {5- (2-fluorothienyl)}-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    4- {2- (5-acetylthienyl)}-2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -3 ( 2H ) -furanone;
    2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- {2- (5-methylthienyl)}-3 ( 2H ) -furanone;
    2-ethyl-2-methyl-5- {4- (methylsulfonyl) phenyl} -4- {2- (3-methylthienyl)}-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (2-furanyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (3-furanyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {5- (3-fluorofuranyl)}-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {5- (2-fluorofuranyl)}-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {4- (2-fluorofuranyl)}-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (3-thienyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (2-thienyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {4- (2-fluorothienyl)}-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {5- (2-fluorothienyl)}-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {5- (3-fluorothienyl)}-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -4- (2-benzo [b] thienyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -4- (2-benzo [b] furanyl) -2,2-dimethyl-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (2-naphthyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (1-naphthyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (2-pyridyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (3-pyridyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (4-pyridyl) -3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {4- (1-N-methylpyrazolyl)}-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {4- (1-N-ethylpyrazolyl)}-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- {4- (1-N-isopropylpyrazolyl)}-3 ( 2H ) -furanone;
    5- {4- (aminosulfonyl) phenyl} -2,2-dimethyl-4- (4-pyrazolyl) -3 ( 2H ) -furanone.
    [20" claim-type="Currently amended] 1,2-Diarylether in the presence of a base to synthesize 4,5-diaryl-2,2-dimethyl-3 ( 2H ) -furanone derivatives of Formula (I) Use of α-bromobutyryl cyanide in reaction with rice fields:

    Food,
    Y is selected from alkylthio and alkylsulfonyl;
    X is selected from hydrido, halo and alkyl groups; And AR is as defined in formula (I) of claim 1.
    [21" claim-type="Currently amended] A pharmaceutical composition for treating an inflammatory disease comprising a compound of any one of claims 1 to 19 in a therapeutically effective amount.
    [22" claim-type="Currently amended] A pharmaceutical composition for treating an inflammation-related disease comprising a compound of any one of claims 1 to 19 in a therapeutically effective amount.
    [23" claim-type="Currently amended] A pharmaceutical composition for treating cyclooxygenase-2 mediated disease comprising a compound of any one of claims 1 to 19 in a therapeutically effective amount.
    [24" claim-type="Currently amended] A pharmaceutical composition for treating diseases susceptible to a nonsteroidal anti-inflammatory agent comprising a compound of any one of claims 1 to 19 in a therapeutically effective amount.
    [25" claim-type="Currently amended] Use of the sulfoxide compound of formula (VI) as a prodrug corresponding to the sulfone compound of formula (VII):

    Ⅵ Ⅶ
    Food,
    X, R 1 and R 2 , and AR are as defined in formula (I) of claim 1.
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    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    法律状态:
    1999-04-14|Priority to KR1019990013170A
    1999-04-14|Priority to KR1019990013170
    1999-07-22|Priority to KR1019990029779
    1999-07-22|Priority to KR1019990029779A
    1999-09-13|Priority to KR1019990039043
    1999-09-13|Priority to KR1019990039043A
    2000-03-31|Priority to KR1020000016866A
    2000-03-31|Priority to KR1020000016866
    2000-04-04|Priority to KR1020000017647
    2000-04-04|Priority to KR1020000017647A
    2000-04-12|Application filed by 서경배, 주식회사 태평양
    2001-12-19|Publication of KR20010111584A
    优先权:
    申请号 | 申请日 | 专利标题
    KR1019990013170A|KR20000066223A|1999-04-14|1999-04-14|Diaryl-3furanone derivatives and cyclooxygenase-2 inhibitor composition containing thereof|
    KR1019990013170|1999-04-14|
    KR1019990029779|1999-07-22|
    KR1019990029779A|KR20010010728A|1999-07-22|1999-07-22|2,2-Dialkyl-4,5-diaryl-3furanone derivatives as cyclooxygenase-2 inhibitor|
    KR1019990039043A|KR20010027342A|1999-09-13|1999-09-13|Sulfonamide derivatives of 2,2-dialkyl-4,5-diaryl-3furanone as cyclooxygenase-2 inhibitor|
    KR1019990039043|1999-09-13|
    KR1020000016866A|KR20010094519A|2000-03-31|2000-03-31|Synthetic Method of 2,2,4,5-tetrasubstituted 3-furanone derivatives|
    KR1020000016866|2000-03-31|
    KR1020000017647|2000-04-04|
    KR1020000017647A|KR20010094161A|2000-04-04|2000-04-04|2,2-Dimethyl-4,5-diaryl- 3furanone derivatives and selective cyclooxygenase-2 inhibitors and a pharmaceutical composition thereof|
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