• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    Compounds of the formula: wherein each of R1, R2 and R3, wnich can be the same or different, is hydrogen, chloro, bromo, fluoro, methyl, ethyl, methoxy, amino, hydroxy or nitro; R4 is hydrogen or alkyl of 1 to 7 carbon atoms; R5 is hydrogen or a straight or branched alkyl group of 1 to 5 carbon atoms or a phenyl group; and R6 is hydrogen or an alkyl group of 1 to 7 carbon atoms or a substituted or unsubstituted benzyl, X is -CH2-, -CHOH-or -CH=CH- and n is 0-4; provided that R5 and R6 are simultaneously hydrogen only when n is 4 and X is -CH=CH-; and their non-toxic pharmaceutically acceptable acid addition salts and mixtures thereof exhibit valuable pharmacological activity and are useful in the treatment of mammals, especially as antithrombotic agents. Furthermore. some of the compounds have proved to possess anti- hypertensive or β-btocking activity. Antimicrobial and antifungal properties have also been found. Processes for the preparation of these compounds are described, as are novel pharmaceutical compositions comprising at least one of the compounds of their salts.
    公开号:SU1162372A3
    申请号:SU823385206
    申请日:1982-02-04
    公开日:1985-06-15
    发明作者:Йоханнес Карьялайнен Арто；Ойва Антеро Куркела Кауко；Сулеви Леннарт Пархи Сеппо
    申请人:Фармос Ихтюмя Ой (Фирма)；
    IPC主号:
    专利说明:

    1 The invention relates to a process for the preparation of novel derivatives of substituted imidazole of the general formula. CH (CHg) „kI where R ,, R and EZ are pairwise identical or different and denote hydrogen, methyl or chlorine, and always one of the radicals R, R and R is hydrogen or all three radicals R ,, R and Rj are simultaneously hydrogen; R4 is hydrogen. C -C-alkyl of the normal structure or phenyl; Rg is hydrogen, C, alkyl of the normal structure, unsubstituted or 4-chloro- or 4-methyl-substituted benzyl, and always one of the radicals RJ or R is hydrogen; n 0-4, with n 0, R ,, R or Rr not methyl, or their hydrochlorides, which have an „„ tigipertenzivnii or antimicrobial activity. The purpose of the invention is a process for the preparation of compounds of the general formula (I) or their hydrochlorides having antihypertensive or antimicrobial activity. The goal is achieved in that according to the method, which implies that the aldehyde is total 1 O Aj II I RAvAdx where R and R have the indicated values, is reacted with arylalkyl magnesium bromide of the formula Kg. RI (CH 2) MdVg (III) where R ,, Rj, R and p have the indicated meanings. 50 5 2 with the selection of the target product in free form or in the form of hydrochlorides. In the Examples below, where H is given by NMR spectra, they are taken on an R 24 instrument from Perkin-Elmer using tetramethylsilane as the external standard, from which the chemical shifts are presented (6, part per million). The letters s, d, t, m are used to denote a singlet, a doublet, a triplet, and a multiplet. In the same relation, the number of hydrogen atoms is also indicated. The compounds listed as bases are taken in deuterated methanol, deuterated acetone or deuterated chloroform, while the spectra of the compounds indicated as hydrochlorides are taken in deuterium oxide. The presented NMR spectra are recorded on the instrument of the company Bruker WB-80 DS. Example 1; (2,6-dimethylphenyl) hydroxymethyl -2-ethylimidazole. 6.12 g of dried magnesium chips shreds 100 ml of dry tetrahydrofuran (THF). The mixture is heated to a bale .. w. and then 46.7 g of 1-bromo-2,6-dimethylbenzene and 100 ml of dry THF are added dropwise to the, T / I, 46.7 g at a rate ensuring a slight boiling up of the mixture. After the addition was complete, the reaction mixture was boiled for an additional 30 minutes, then cooled to 50 ° C and 10.45 g of 2-ethyl-4-imidazolaldehyde was slowly added in small portions. At the end of the addition, the mixture is boiled for 4 hours. Then the reaction mixture is cooled and poured into 200 mp of cold water. containing 20 ml of concentrated hydrochloric acid. A portion of the THF was distilled to a small volume, the distilled THF was replaced with water, and the mixture was washed twice with 50 ml of chloroform. The aqueous layer is alkalinized to pH 8 with caustic soda, the precipitated precipitate is washed with water and added to 100 ml of 4N. caustic soda solution, after which the mixture is vigorously stirred for an hour. The precipitate is filtered off, washed several times with water and dried. After recrystallization of the crude product from ethanol: with water, 7.8 g of product are obtained with so pl. 164166 0. SAL (H) spectrum: 1.25 (t, 3H); 2.33 (s, 6H); 26.81 (q, 2H); 4.86 (S, IH + HjO); B, 22 (s, 1h); 6.36 (s, 1H); 7.00 (s, 3H). Nuclear Magnetic Resonance Spectrum (C): 13.25 (q, 1C); 20.91 (q, 2C); 22.36 (t, 1C); 67.49 (d, 1C); 118.17 (d, 1C); 128.25 (s, 2C), 129.95 (d, 2C); 138.06 (d, 1C); 139.03 (s, 1C); 139.33 (s, 1C); 151.321 (s, 1C). Example 2. (2,6-dimethyl phenyl) hydroxymethyl -2-n-butylimideol. Reproduced the method of example 1, except that instead of 2-ethyl-4-imidazolaldehyde take 2-n-butyl-4-ynidazolapdegid. M.p. obtained base 152-156 C. Example 3. 4-C2- (2,6-dimethyl fennp) -1-hydroxyethyl) -2-methyl imide sol. The procedure of Example 1 was repeated, except that 2-methyl-4-imidazolapdehyde and (2,6-dimethylphenyl) bromoethane are taken as starting compounds. NMR spectrum of the SP): 2.27 (s, 6H); 2.35 (s, 3N); 3.16 (t, 2H); 4.68 (t, 2H); 6.65 (s, 1H); 6.98 (s, 3N). Example 4. 4Cgr- (2,6-dimethylphenyl) hydroxymethyl -2-phenylimidazole The procedure of Example 1 was reproduced, except that 2-phenyl 4 imidazolaldehyde was used. M.p. base obtained 181-183 C. NMR spectrum (n): 2.37 (s, 6H); 4.96 (s, 1H + HjO); 6.34 (d, 1H); 6.80 (d, 1H); 7.02 (s, 3N); 7.35 (m, 3N); 7.86 (m, 2H). Example 5. (.- (2,6-dimethyl phenyl) hydroxymethyl 3-2-methyl imidazal Reproduced procedure of example 1, except that use 2-methyl-4-imidazolapdegid. The resulting compound has a mp. 176-177 C Example 6 (2,3-dimethylphenyl) hydroxymethyl -2-methylimidazole. The procedure of Example I was reproduced with the exception that 2-methyl-4-imidazolaldehyde and 2,3-dimesh1-1-bromobenzene were used as starting compounds. obtained base 176-178 C. Yield 68%. By the same method, for example, the following compounds are obtained: 4-f3- (2, b-dimethylphenyl) -1-hydroxypropyl -2- ethylnmidazole with a mp (base) 18b-187 s; (2-chlorophenyl) -1-hydroxy-bu .thyl -2-methylimidazole, mp (hydrochloride) 134-136 ° C; 4-G4- (2 , 6-dichlorophenyl) -1-hydroxybutyl -2-methylimidazole, mp. (Hydrochloride) 150-151 C. 4- 5- (2,6-dimethylphenyl) -1-hydroxypentyl -2-methylimidazole, mp. (base) 112-115s, (2,3-dimethylphenyl) hydroxymethyl-3-benzylimidazole, yield 55%, mp. (base) 120-130 ° C, NMR spectrum (n): 1.74 (s, 3N) ; 2.21 (s, 3N); 5.17 (q, 2H); 5.67 (s, 3N); 6.3 (s, 1H); 7.0-7.4 (t, 9H); NMR spectrum (s): 14.38i 20.37; 49.07, 64.72; 123.75; 125.42; 127.05; 127.99i 128.84, 129.20; 129.32; 133.44; 136.26; 136.62; 138.80, 139.22; - (3-methylphenyl) hydroxymethyl-3-benzylimidazole, yield 52%, so pl. (base) 128-13lc, NMR spectrum (n): 2.25 (s, 3N); 5.02 (q, 2H); 5.59 (s, 1H); 6.50 (s, 1H); 6.9-7.3 (t, 9H); 7.22 (d, 1H); - (benzyl) hydroxymethyl -3-benzylimidazole, yield 63%, so pl. (base) 156-160 s, NMR spectrum (n): 3.06 (d, 2H); 4.72 (t, 1H); 5.0.7 (s, 2H); 6.9-7.4 (t, 12H); (4-chlorophenyl) hydroxymethyl-3-benzylimidazole, 61% yield, m.p. (base) 160-163 C, NMR spectrum (s): (q, 2H); 5.61 (s, 1H); 6.54 (s, 1H); 6.9-7.4 (t, YUN); 4- (3-phenyl-1-hydroxypropyl) -3-benzylnmidazole, yield 59%, mp. (base) 147-151 ° C, NMR spectrum of CH): 1.9-2.3 (ha, 2H); 2.5-2.8 (t, 2H); 4.48 (t, 1H); 5.16 (s, 2H); 6.92 (s, 1H); 7.00-7.35 (t, YUN); 7.37 (s, 1H); (3,4-dimethylphenyl) -1-hydroxypropyl 3-3-benzylimidazole, yield 68%, mp. (hydrochloride) 152.2-155, NMR spectrum (H) (hydrochloride): 1.92, 2 (t, 2H); 2.19 (s, 6H); 2.552, 75 (t, 2H); 4.60 (t, 1H); 4.95 (h, 2H); 5.48 (s, 2H); 6.75-7.10 (t, 3N); 7.1-7.5 (t, 5H); 7.54 (s, 1H); 8.99 (s, W):) - (2,3-dimethylphenyl) hydroxymethyl-3- (4-chlorobenzyl) imidazole, yield 52%, so pl. (hydrochloride) 204-209С; NMR spectrum (H) (hydrochloride): 1.87 (s, 3N); 2.26 (s, 3N); 4.57 (s, 2H); 5.86 (s, 1H); (s, 1H); 7.17, 5 (t, 7H); 9.08 (d, W); - (Z-methylphenyl) -hydroxymethyl-3- (4-chlorobenzyl) imidazole, yield 59%, so pl. . (hydrochloride) 179-182 s, NMR С NM): 2.31 (s, 3N); 4.55 (wide signal, 2H), 5.41 (s 2H); 5.78 (s, 1H); 6.98 (s, 1H); /, 0-7.4 (t, 8b; 8.86 (d, 1H); 4- (2-phenyl-1-hydroxyethyl) -3- (4-chlorobenzyl) imidazole, 58% yield, m.p. (base 18 -188 ° С, NMR Spectrum СН): 3.04 (d, 2H); 4.36 (s, 2H) 4.70 (t, 1H); 5.21 (s, 2H); 6, 9-7.4 (t, YUN); 7.66 (s, 1H); - (4-chlorophenyl) -hydroxymethyl -3- (4-chlorobenzyl) imidazole, 60% yield, mp. (Hydrochloride) 189 -195 s, NMR spectrum (n) (hydrochloride): 4.58 (wide band, 2H) / 5.47 (s, 2H); 5.84 (s, 1H); 6.97 (q, 1H); 7, 2-7.5 (s, 8H); 8.90 (s, 1H); 4- (3-phenyl-1-hydroxypropyl) -3- (4-chlorobenzyl) imidazole, 65% yield, mp. ( base) 135-137s, NMR spectrum (l): 1.9-2.3 (t, 2H); 2.6-2.8 (ha, 2H); 4.42 (t, 1H); 5.10 (s, 2H); 6.85 (d, 1H); 6.9-7.3 (t, 1H); (3,4-dimethylphenyl) -1-hydroxypropyl - 3- (4-chlorobenzyl) midazol, 63% yield, mp (base) 126130 ° C, NMR spectrum (n): 1.8-2.3 (t, 2H); 2.20 (s, 6H); 2.5-2 , 8 (t, 2H); 4.35 (wide band, 1H), 5.11 (s, 2H); 6.7-7.4 (ha, 9H) i 4-Gob- (2,3-dimethylphenyl ) -hydroxymethyl -3- (4-methylbenzyl) imidazole, 65% yield, mp. (hydrochloride) 18519. | ° C, NMR): 1.78 (s, 3N) 2.20 (s, ZN); 2.33 (s, 3N); 5.42 (s, 2H); 5.6 (wide band, 1H); 5.99 (s, 1H); 6.63 (s, Ш); 7.0-7.4 (t, 7H); 8.72 (d, 1H); .- (3-met1Shphenyl) hydroxymethyl1, -3- (4-methylbenzyl) imidazole, yield 57%, mp. (hydrochloride) 152-155 ° C, NMR spectrum (H) (hydrochloride): 2.30 (s, 3N); 2.33 (s, 3N); (wide band, 1H), 5.31 (s, 2H); 5.85 (s, 1H); 6.96 (s, W); 7.1 (s, 8H); 8.52 (s, 1H); 4- (2-phenyl-1-hydroxyethyl) -3- (4-methylbenzyl) imidazole, yield 59%, mp. (base) 177-180 C, spectrum (n): 2.33 (s, 3N); 3.08 (d, 2H) 4.75 (t, 1H); 5.04 (s, 2H); 6.8-7.5 (t, YUN); - (4-chlorophenyl) hydroxymethyl J. .. -3- (4-methylbenzyl) imidazole, yield 59%, mp. (hydrochloride) 199-202 s, NMR spectrum (PR: 2.34 (s, 3N); 4.89 (s, 2H); 5.43 (s, 2H); 5.88 (d, 1H); 7, 17 (wide band, 5H), 7.35 (s, 4H); 8.90 (d, 1H); 4- (3-phenyl-1-hydroxypropnl) -3- (4-methylbenzyl) imidazole, 66% yield m.p. (hydrochloride) 156-159 ° C, NMR spectrum of CH): 1.8-2.3 (t, 2H); 2.3 (s, 3N); 2.5-2.8 (t, 2H); 4.5-4.8 (t, 1H); . 5.42 (s, 2H); 7.0-7.4 (t, YUN); 8.7 (d, W); (3,4-dimethylphenyl) -1-hydroxypropyl-3- (4-methylbenzyl) imidazole, yield 70%, m.p. (hydrochloride) 159163 ° C, NMR spectrum (n): 1.8-2.3 (ha, 2H); 2.23 (s, 6H); 2.35 (s, 3N); 2.52, 7 (t, 2H); 4.5 (wide band, 1H); 4.6-4.7 (t, 1H); 5.40 (s, 2H); 6.7-7.4 (ha, 8H); 8.74 (d, 1H); (2,6-dimethylphenyl) -1-hydroxypropip-3-benzylimidazole, yield 66%, so pl. (hydrochloride) 148-151 ° C, NMR spectrum (s): 1.75-2.10 (t, 2H); 2.24 (s, 6H); 2.6-3.0 (ha, 2H); 4.74 (t, 1H); 4.94 (s, 2H); 5.57 (s, 2H); 6.98 (s, 3N); 7.37 (s, 5H); 7.56 (s, W); 9.01 (d, 1H); D-C2- (2,6-dimethylphenyl) -1-hydroxyethyl j-3-benzylimidazole, yield 51%, so pl. (base) 184-187 s, NMR spectrum (s): 20.19 (2C); 37.42, 49.28-, 65, ZZ; 126.631 127.08; .127.48; 128.57; 128.87, 129.48 135.35; 135.89; 137.13; 138.01, 138.83. (2, .6-dimethylphenyl) -1-hydroxypropyl-3-ethylimidazole, 61% yield, m.p. (hydrochloride) 178-179 0, NMR spectrum) (hydrochloride): 15.76 19.95 (2C); 26.70; 36.00, 43.84; 64.67; 117.66; 126.78; 129.08; 136.23; 136.96; 138.60; 139.00, (2,6-dimethylphenyl) -1-hydroxypentyl-3-ethylimidazole, yield 64%, mp. (hydrochloride) 117-120 ° C, NMR spectrum (s) (hydrochloride), 15.77, 19.95 (2C); 27,215; 30.0; 30.45; 36.45, 43.80; 64.60; 117.70; 128.96; 136.20; 136.68; 138.71, 140.10; (2,6-dimethylphenyl) -1-hydroxyethyl1-3-ethylimidazole, yield 66%, mp. (base) 185-189 ° C, NMR spectrum (H): 1.28 (t, 3N); 2.23 (s, 6H); 2.8-3.4 (t, 2H); 3.91 (q, 2H); 4.64, 85 (t, 1H); 6.85 (s, 1H); 6.97 (s, 3N); 7.58 (s, 1H). Antihypertensive properties of imidazole derivatives of the general formula (1) are investigated by the following experiments. Normal-weight Sprague-Dawley rats are first anesthetized. 711623728
    sy under the action of urethane. After this, the diffusion method pa agar
    The second femoral artery is connected through the following standard OP1-anis-polyethylene tube with sensors: Staphylococcus aureus, Streptococcal pressure. Then in the femora-coccus pyogenes, Escherichia coli,
    The vein is injected as a test - 5Proteus rairabilis, a Pseudomonas aerosol, and with the help of stocks-Tiinosis, Candida alhicans, Aspersxil devices, a niger is recorded. Toto pulse and blood pressure. In this way, the pre-antimicrobial activity of certain imidazole or their hydrochlorides is divided in vitro according to quality, it is possible to obtain compounds that have been tested for antimicrobial and have valuable fungus activity using pharmacological.
    Antihypertensive activity of compounds of general formula (I)
    Compiling Derivatives Replacement Table 1
    He Nz
    n, .l
    0.01 (i.v.)
    W CHZ CHv
    1-3 (i.v.)
    NK: SNZ he s
    1-10
    .N (i.v.)
    NH CH3
    CHj
    Cg
    3 (i.v.)
    „, With /) W si
    tjHj OH
    N (nSN, (NgCHO
    J
    Usage not described
    5 OH
    H,
      ji
    N
    17
    Usage not described
     HE
    ten
    Usage not described
    ten
    Usage not described
    NZS)
    25
    Usage is not described - 3-10 g (U,. OW / Y -iiT CHj CHj 0.03-3 (U (i.v. 1162372 ± 1 10 Continuation of the table. Use is not described / ush is not described
    33
    Antimicrobial activity of compounds of general formula
    (n,
    n / N-eNg% O
     j
    CH, N
    Cl
    NHS NH
    table 2
    SNS
    he nhi
    TO
    ,,
    N
    Usage not described
    cn he
     .n-ch5)
    n, si
     SNS
    cJH, g)
    N- | -CH.CHCHr (
    O
    Usage not described
    5 OH
    N
    Usage not described
     .sn.
    R
    NH
    Usage not described
    -dH
    UK
    Usage not described
    / (n, l afi „
    / N OH CiH-No. L3; ,
    there is
    Usage not described
    13
    CH, i
    (
    about SNS
    LD data for intravenous administration of the general formula
    Compound
    14 Continuation of table 2
    i i v 3
    mg / kg
    PP
    35
    50
    he
    NzS- / G X§
    CH,
    NH
    300
    CH,
    权利要求:
    Claims (1)
    [1]
    A method of obtaining derivatives of substituted imidazole of the general formula!
    where R ^ and Ry have the indicated meanings, are reacted with an arylalkyl magnesium bromide of the general formula III where R ( , R , Ry and η have the indicated meanings, with the isolation of the target product in free form or in the form of hydrochlorides.
    类似技术:
    公开号 | 公开日 | 专利标题
    SU1162372A3|1985-06-15|Method of obtaining derivatives of substituted imidazole or their hydrochlorides
    HU187773B|1986-02-28|Process for preparing substituted imidazole derivatives maceutical compositions containing such compounds
    SU1074404A3|1984-02-15|Method of producing imidazole derivatives or their salts
    LV12887B|2003-01-20|N-heterocyclic derivatives as nos inhibitors
    FI85371C|1992-04-10|FRAMEWORK FOR FARMING OF PHARMACEUTICAL PRODUCTS.
    US4107314A|1978-08-15|Antifungal thio-alkyl-imidazole derivatives
    US3956262A|1976-05-11|Triazenoimidazoles
    LU85747A1|1986-08-04|IMIDAZOLE DERIVATIVES, PREPARATION AND USE THEREOF AND PHARMACEUTICAL COMPOSITIONS CONTAINING DERIVATIVES
    US3452040A|1969-06-24|5,5-disubstituted hydantoins
    US4598077A|1986-07-01|Amidine derivatives and cardiotonic compositions
    EP0056866B1|1985-06-19|Phenylpiperazine derivatives of heterylphenols and hetarylanilines, their preparation and their pharmaceutical compositions
    WO1990003972A1|1990-04-19|Derivatives of metal-4 |-2 ethyl))-5 thiazole
    US4946862A|1990-08-07|Thiophene derivative and process for preparing the same
    US2213469A|1940-09-03|Aralkyl morpholines
    US2723269A|1955-11-08|Piperidino tertiary amino alcohols
    FR2503705A1|1982-10-15|PHENETHANOLAMINE DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION
    SU828965A3|1981-05-07|Method of preparing hexahydro-1,4-oxazepins or their salts
    US4432991A|1984-02-21|Therapeutically active 3-amino-1-phenyl|-2-pyrazolines
    CA2128560A1|1995-01-24|Substituted piperazines, their preparation process and pharmaceutical compositions containing them
    US4407816A|1983-10-04|3-Substituted-2-propenimidamides and method of manufacturing the same
    US4179442A|1979-12-18|4-|-5-phenyl-oxazolidin-2-one
    US4200760A|1980-04-29|Imidazolylalkylthioalkylamino-ethylene derivatives
    EP0461012B1|1994-04-20|methylpiperazine derivatives, process for their preparation and their use in therapy
    US2991289A|1961-07-04|Derivatives of 1-aminopropane
    US4734428A|1988-03-29|Aminoethylimidazole and cytoprotective and gastric antisecretory composition containing the same
    同族专利:
    公开号 | 公开日
    AU8014482A|1982-08-12|
    EP0058047B1|1984-11-07|
    NZ199631A|1985-02-28|
    JPS57149273A|1982-09-14|
    JPH0261458B2|1990-12-20|
    IE820241L|1982-08-05|
    EP0058047A1|1982-08-18|
    GB2092569B|1984-09-19|
    DK157545B|1990-01-22|
    FI76568B|1988-07-29|
    IL64922A|1986-01-31|
    AU552322B2|1986-05-29|
    DK630786D0|1986-12-29|
    DK630786A|1986-12-29|
    FI76568C|1988-11-10|
    DK157545C|1990-06-11|
    DE3261153D1|1984-12-13|
    USRE32400E|1987-04-14|
    DK158351C|1990-10-08|
    DK158351B|1990-05-07|
    HU187564B|1986-01-28|
    IE52362B1|1987-09-30|
    NO820340L|1982-08-06|
    US4514412A|1985-04-30|
    DK44682A|1982-08-06|
    ZA82717B|1983-01-26|
    NO155884C|1987-06-17|
    DD210451A1|1984-06-13|
    CA1176259A|1984-10-16|
    GB2092569A|1982-08-18|
    FI820140L|1982-08-06|
    AT10192T|1984-11-15|
    IL64922D0|1982-04-30|
    NO155884B|1987-03-09|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    RU2465269C2|2006-12-18|2012-10-27|Ф. Хоффманн-Ля Рош Аг|4-imidazolines as taar ligands|US3356645A|1964-04-20|1967-12-05|Shell Oil Co|Process for curing epoxy resins with a salt of an imidazole and compositions thereof|
    FR2122395B1|1971-01-19|1975-08-01|Berlin Chemie Veb|
    DD96070A1|1971-02-23|1973-03-12|
    JPS611022B2|1978-05-15|1986-01-13|Takeda Chemical Industries Ltd|
    US4220654A|1979-06-04|1980-09-02|Merck & Co., Inc.|Cyclic imidazole cyanoguanidines|
    AU518569B2|1979-08-07|1981-10-08|Farmos-Yhtyma Oy|4-benzyl- and 4-benzoyl imidazole derivatives|
    GB2069481B|1980-02-13|1983-07-27|Farmos Oy|Substituted imidazole derivatives|
    JPS624387A|1985-07-01|1987-01-10|Nec Corp|Printed circuit board|GB2101114B|1981-07-10|1985-05-22|Farmos Group Ltd|Substituted imidazole derivatives and their preparation and use|
    FI833794A0|1983-10-18|1983-10-18|Farmos Oy|SUBSTITUERADE 2-MERKAPTO-IMIDAZOLER|
    FI844786A0|1984-12-04|1984-12-04|Farmos Oy|TERAPEUTISKT UTNYTTJBAR FOERENING.|
    GB8523255D0|1985-09-20|1985-10-23|Shell Int Research|Imidazoles|
    GB8626287D0|1986-11-04|1986-12-03|Ucb Sa|Substituted 1h-imidazoles|
    JPS63150266A|1986-12-12|1988-06-22|Mitsui Petrochem Ind Ltd|Benzylimidazole derivative|
    GB2206880B|1987-07-16|1991-04-24|Farmos Oy|Optical isomers of an imidazole derivative|
    GB2210875B|1987-10-09|1991-05-29|Farmos Oy|Aromatase inhibiting 4-imidazoles|
    GB8810067D0|1988-04-28|1988-06-02|Ucb Sa|Substituted 1-alkyl-benzamides|
    AU627559B2|1989-03-30|1992-08-27|Farmos-Yhtyma Oy|Novel aromatase inhibiting 4-imidazoles|
    US5073566A|1989-11-30|1991-12-17|Eli Lilly And Company|Angiotensin ii antagonist 1,3-imidazoles and use thereas|
    US5401851A|1992-06-03|1995-03-28|Eli Lilly And Company|Angiotensin II antagonists|
    FR2732017B1|1995-03-21|2000-09-22|Inst Nat Sante Rech Med|NOVEL IMIDAZOLE DERIVATIVES AND / OR HISTAMINE H3 RECEPTOR AGONISTS AND / OR AGONISTS, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATIONS|
    US6329369B1|1997-12-04|2001-12-11|Allergan Sales, Inc.|Methods of treating pain and other conditions|
    US6841684B2|1997-12-04|2005-01-11|Allergan, Inc.|Imidiazoles having reduced side effects|
    WO2004078715A1|2003-03-07|2004-09-16|Astellas Pharma Inc.|Nitrogenous heterocyclic derivative having 2,6-disubstituted styryl|
    BRPI0514812A|2004-09-01|2008-06-24|Astellas Pharma Inc|piperidine derivative or pharmaceutically acceptable salt thereof|
    DK2847157T3|2012-05-08|2016-02-08|Lonza Ag|PROCEDURE FOR PREPARING 2--1-PROPANAL|
    CA2866424A1|2012-05-08|2013-01-24|Lonza Ltd.|Method for preparation of medetomidine|
    WO2012172119A2|2012-05-08|2012-12-20|Lonza Ltd|Method for the preparation of medetomidine|
    ES2565065T3|2012-06-28|2016-03-31|Lonza Ltd|Method for the preparation of 2--1-propanal with chloroacetone|
    JP5777841B2|2012-06-28|2015-09-09|ロンザ・リミテッド|Process for the preparation of medetomidine using chloroacetone|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    GB8103620A|GB2092569B|1981-02-05|1981-02-05|Substituted imidazole derivatives and their preparation and use|LV920314A| LV5062A3|1981-02-05|1992-12-17|Method of obtaining substituted imidazole derivatives or their hydrochlorides|
    LTRP764A| LT2217B|1981-02-05|1993-07-07|THE BUDGET FOR RECEIVING IMIDAZOLS DERIVED OR HYDROCHLORIDE|
    [返回顶部]