• 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:
    Bicyclic thiadiaza compounds, especially 1,3-diazacyclopent-2- eno[2,1-b]-(1-thia-3-azacycloalkanes) of the general formula <IMAGE> whose 1,3-diazacyclopent-2-ene ring can have another double bond, Alk is lower alkylene which separates the thia from the aza atom by 2-4 carbon atoms, Ar1 and Ar2 are, independently of one another, optionally substituted phenyl, pyridyl or thienyl, and n is 0, 1 or 2, with the proviso that at least one of the radicals Ar1 and Ar2 is different from phenyl when Alk is ethylene and the 1,3-diazacyclopent- 2-ene ring is an imidazole ring, and the salts thereof, and intermediates of the formula Va or Vb <IMAGE> have valuable pharmacological properties.
    公开号:SU873886A3
    申请号:SU782632647
    申请日:1978-07-06
    公开日:1981-10-15
    发明作者:Гешке Рихард；Джорж Феррини Пьер
    申请人:Циба-Гейги Аг(Фирма)；
    IPC主号:
    专利说明:

    The aim of the invention is to obtain new compounds of general formula I, which expand the range of means of action on a living organism.
    The goal is achieved by the fact that according to the method for preparing a compound of general formula I or their salts, a compound of general
    T v t
    (0) n
    Ae.TSi,,.
    Aft
    where Ar, Arj., n and Alk have the indicated meanings;
    The X-reactive esterified ester hydroxyl group is cyclized in a low-boiling brush of an organic solvent solvent in the presence of a base, and the final product is isolated in free form or as a salt and / or as isomers of a mixture or as individual isomers.
    The compounds of general formula I possess valuable pharmacological properties, in particular, anti-inflammatory activity and anti-rheumatic effect, as can be shown in animal experiments. For example, in the KaoN n-pfotenoedem test in rats with a mouth dose of less than about 10 mg / kg or in Terpent 5 pp 1 eur 1 11 S test in rats with a mouth dose of 30 to 100 mg / kg, the corresponding compounds of general formula I exhibit anti-inflammatory, respectively, exudative activity. In particular, the unsaturated compounds in the Adjurans-Arthritis test on the roof. Sah-when administered through the mouth a dose of 10 to 30 mg / kg also show excellent activity.
    Example 1. A suspension prepared from 7 ml of 1,2-dibromoethane, 7 g of sodium carbonate and 55 ml of isopropyl alcohol is stirred at room temperature and mixed with a suspension of 4.7 g of 4,5-difenylimidazolidin-2-ton in an hour 110 ml of 1.5% solution of sodium hydroxide. The reaction mixture is heated at reflux temperature for 7 hours, after which isopropyl alcohol and dibromoethane are removed on a rotary evaporator. The remaining suspension is extracted with toluene. The toluene extract is washed with brine, dried with sodium sulfate and evaporated. The residue is chromatographed on silica gel. After removal of the nonpolar prikyus, ethyl acetate is eluted with a mixture of ethyl acetate and methyl alcohol taken in a ratio of 99: 1, 5, b-diphenyl-2,3,5, b-tetrahydroimidazo 2,1-b thiazole as a colorless oily substance, which spontaneously crystallizes to form a white crystalline product with a melting point of IO-C C (sintering temperature of 103 ° C). After recrystallization from methylene chloride / ethyl ether, the melting point is 132135 ° C.
    PRI mme R 2. A suspension containing 3.5 ml of 1,2-dibromoethane, 3.5 g of carbon dioxide sodium in 30 ml of isopropy-t
    After one hour, while stirring at room temperature, they are mixed with a suspension of 3 g of 4,5-dianisyl-2-mercaptoimidazole in 50 ml of 1.5% sodium hydroxide solution. The reaction mixture is heated at its boiling point. After that, isopropid alcohol and dibromoethane are removed on a rotary evaporator, the remaining suspension is mixed with 10 ml of a 20% aqueous solution of hydroxide to gsi, after which it is extracted with ethyl ester of acetic acid. The organic phase is washed with brine, dried with sodium sulfate and then evaporated. From the obtained residue, after recrystallization from a mixture of toluene and petroleum ether, 5,6-di- (p-methoxyphenyl) -2,3-dihydroimidazoG2,1-β1-thiazole is isolated, melting point 152-154 ° C. Its hydrobromide melts at 200-206 C. Dialogically, by reacting with 2-bromo-butanol, 5 b, di (p methoxy phenyl) -2, 3-dimethyl-2,3-dihydroimidazoG2, 1-b thiaole are obtained. from m.p. 120121 C.
    Example 3. 14.8 g of 4,5-di (p-methoxyphenyl) -2-beta-hydroxyethyl mercaptoimidazole are dissolved in 50 ml of absolute pyridine and with stirring and temperature approximately inside the reaction vessel, the KI solution is added dropwise 15.8 g benzenesulfonyl chloride in 60 ml of absolute pyridine. Immediately after this, the reaction mixture is stirred for 60 hours at. The reaction mixture is then poured into ice water and extracted with dichloromethane. The combined and washed with water three times dichloromethane extracts are dried with sodium sulfate and then evaporated to dryness. The viscous oily product is crystallized from a mixture of toluene and petroleum ether. 5, b-di- (p-methoxyphenyl) -2,3-dihydro t2,1-b thiazole obtained in this way has a melting point of 152-154 ° C.
    The source material can be obtained, for example, as follows.
    2.5 g of sodium are dissolved in 220 ml of ethyl alcohol. 35 g of 4,5-dianisylimidazolin-2-thione are added to the solution obtained. Get the suspension. Within 2 min to this suspension
    15.7 ml of 2-chloroethanol are added dropwise at room temperature (stirred). The reaction mixture is stirred for 1 hour at and then at reflux temperature for 4 hours. Immediately after this, the resulting suspension is evaporated to dryness. The residue is purified using a mixture of acetone and water,
    EXAMPLE 4 To a solution of 23 g of para-toluenesulfonyl chloride in 80 ml of pyridine a solution of 20 g of 2-2-oxyethylthio-4 (5) -3-pyridyl-5 (4) -phenylimidazole is added with stirring and temperature. The reaction mixture is stirred for 16 hours at, then it is poured into ice-water and extracted with diethyl ether. After washing the ether extract with water and drying with sodium sulfate, evaporation is carried out, resulting in a residue from which, after chromatography on silica gel with toluene and ethyl acetate, and after recrystallization of the corresponding fraction from ethyl acetate, an isomeric mixture of 5 (b) - ( 3-pyridyl) -6 (5) fenil-2, 3-dihydro-imidazo C2 D-B thiaool as a white crystalline product with melting point ISO-Sl C.
    The starting material can be obtained in the following manner.
    10.8 g of benzylpyridine- (3) -ketone together with 40 ml of pyridine and a solution of Om 8 F hydroxyamide hydrochloride in 15 ml of pyridine are stirred for 6 hours at. Then the reaction mixture was poured into ice water and stirred for 15 minutes. The precipitated crystalline product is filtered on a fillet, washed with water and dried under high vacuum. The result is benzylpyridyl- (3) -ketonoxime with a melting temperature of 122–12b C.
    To 20 ml of pyridine mixed with a solution of 8.5 g of benzylpyridyl- (3) -etonoxime in 20 MP is added. drops 5 min. solution, containing 7.7 g of paratoluenesulfonyl chloride in 15 MP of pyridine. The reaction mixture is kept for 24 hours in the refrigerator and then poured into ice water. After prolonged stirring, the resulting oily product solidifies to form a crystalline product. The resulting crystalline product is filtered on a suction filter, washed with water and dried in a BHcoKQM vacuum. The result is 11, b g of crude product with a melting point of 87-92 Cg which, however, according to chromatography in a thin layer, still contains aduct. “The resulting product is directly used by the foot of the herd.
    11.6 g of the crude product benzylpyridyl- (3) -keto.noxim-p-tolubsulfoether are suspended in 90 ml of absolute ethanol and a solution of 3.7 g of potassium tert-butylate in 30 ml is added dropwise to the prepared suspension with stirring and temperature. ml of absolute
    ethyl alcohol. The reaction mixture is stirred for 2 hours at. Then the suspension is filtered through a suction filter and the filtrate is immediately used at the next stage.
    3.6 g of sodium thiocyanate are dissolved in 60 ml of ethanol and the prepared solution is mixed with 4.5 ml of concentrated hydrochloric acid. The suspension is subjected to filtration through a suction filter and the filtrate together with an alcohol solution of the obtained alpha-aminobenzylpyridyl- (3) -ketone is kept for 18 hours at the boiling temperature of the reaction mixture under reflux. After cooling from the reaction mixture, 2.8 g of crude 4-phenyl-5-pyridyl (3) -2-mercaptoimidazole is obtained by filtration on a suction filter. The filtrate contains some more product. After recrystallization from a mixture of dimethylformamide and water, a product is obtained with a melting temperature of 290-300 C.
    0.8 g of sodium is dissolved in 200 ml of ethanol. The prepared solution is mixed with 8 g of 4-phenyl-5-pyridyl (3) -2mercaptoimidazole and the reaction mixture is heated under reflux. After the formation of a clear solution, 2 ml of 2-chloroethanol is added dropwise to it and the reaction mixture is heated for 16 hours with a reverse chill at boiling point. Thereafter, the solvent was distilled off from the reaction mixture in vacuo, and the resulting residue was partitioned between water and ethyl acetate. The organic phase is rinsed with water and brine, dried over sodium sulfate and. then evaporation. Crystalline 2- (2-hydroxyethylthio) -4 (5) -3-pyridyl 5 (4) -phenylium aeol is obtained as a residue. After recrystallization from a mixture of ethyl acetate and ethyl alcohol, the product melts at 157-159 ° C. 5,6di- (p-methylphenyl) -2,3,5,6-tetrahydroimidazo G2,1-b thiazole, m.p. 128130C, 5, bd (p-chlorophenyl) -2,3 are obtained. , 5,6 tetrahydroxy "idaeo-G2, .1-h3 thiazole, t. Pl. l2B-l3 (fC.
    Pr and measures 5. 0.69 g of sodium is dissolved in 60 ml of ethyl alcohol and the prepared solution is mixed with 9.36 g of 2-mercapto-4,5-di-p-methoxyphenylimidazole. The reaction mixture is stirred for 30 minutes, after which it is mixed with 3.1 g of 3-chloro-1-propol ol,
    the mixture is kept at reflux temperature for 2 hours, the mixture is cooled, the reaction mixture is filtered until a clear solution is obtained, and the solution is evaporated to dryness. The resulting residue is represented by s-; The crude 2- (3-hydroxypro-5 piltio) -4, 5-di-p-methoxyphenylimidazole, which is crude, is kept for 30 minutes in 50 ml of thionyl chloride at the reflux temperature of the reaction mixture. Then, an excess amount of thionyl chloride is distilled off, 100 ml of additionally added chlorofluoride is removed by distillation, and the residue, together with 100 ml of ethyl alcohol and 50 ml of 5–40% potassium hydroxide solution, is kept under reflux for 4 hours. boiling point of the reaction mixture. After that, the reaction mixture is evaporated on a rotary evaporator, the residue is mixed with a mixture of water and ice and extraction is carried out with ethyl acetate.
    The organic phase is washed with water, 25 is dried and evaporated. The residue obtained is chromatographed on silica gel with a mixture of toluene and ethyl acetate, taken in a 1: 1 ratio. Recrystallization of 30 corresponding fractions from acetone gives b, 7-di-p-methoxyphenyl-2,3f 4,5-tetrahydroimidazo-2, 1-b (1, 3) thiazine, m.p. 189-191 c.
    . Similarly, 5,6-di- (p-35 methoxyphenyl) -2,3,5,6-tetrahydroimidazo G2,1-b3 thiazole is obtained with a melting point of 125-12 bC. P and m er 6. By analogy with that described in Example 5, from 2-mercapto-4,5-di p-chlorophenylimidazole and 2 chloroethanol, 2- (2-hydroxyethylthio) 4,5-du-p-chlorophenylimidazole with m.p. 197-199c, from which, as a result of cyclization in the presence of thionyl chloride 45, 5,5-di-p-chlorophenylimidazo G2,1-S-dihydrothiazole is obtained, mp. 199-204 ° C.
    PRI me R 7. To a suspension of 11.8 g of 5,6-di-p-anisyl-2, 3,5,6-tetra- 50
    hydro-4H-imidazoC2,1-b thiazole. in 30 ml of water; there are 17 ml of 1N. hydrochloric acid and 5 g of M-benol sulfonyl
    L - (+) - glutamic acid. When naked, the mixture dissolves, after which it crystallizes as a result of cooling. 1-5,6-Di-p-aneyl-2, 3,5, b-tetrahydro-4H-imidazo
    2,1-b thiazole-M-benzenesulfonyl-1 (4 -) - glutamate is filtered off, washed with water and treated with a solution of 6Q sodium hydroxide. The resulting mixture is extracted with ethyl acetic acid ester L-5, b-di-p-anisyl2, 3,5,6-tetrahydro-4H-imidazo 2, 1-b and azole.
    Example 8. 4.4 g of 4,5-di {p-methoxyphenyl) -2-b-hydroxyethyl mercapto-imidazole is dissolved in 1 liter of methylene chloride, then slowly adding 1 solution of 2.82 g of m-chloroperbenzoic acid in 125 ml of methylene chloride and stirred for 24 h at room temperature. The reaction mixture is cooled and served on an exemplary soda solution. The organic phases are obtained after washing with brine and drying with sodium sulfate 4,5di- (p-methoxyphenyl) -2- (-oxyethylsulfonyl- .imidazole) with a melting point of 184 ° C. This is dissolved in 15 ml of absolute pyridine and with stirring -5 ° C is added dropwise to a solution of 4, .2 g of benzenesulfonyl chloride in 15 ml of pyridine. The reaction mixture is stirred for 60 h at 0 ° C, poured into ice water, and extracted with ethyl acetate. washed with water, dried with sodium sulfate and evaporated. crystallization from ethanol 5, b-di- (pmethoxyphenyl) -2,3-digi-ro-imidazole G2, 1-b thiaolesulfoxide c, melting point 176 t sec.
    Example 9. 4.5 g of 4,5-di- (pmethoxyphenyl) -2-p) -oxyethylmercaptoimidazole as described in Example 3 are sulphurized with 15.8 g of benzenesulfonyl chloride. To a solution of dichloromethane containing 4,5-di- (p-methoxyphenyl) 2-b-benzenesulfonyloxyethyl mercaptoimidazole, add 5 g of m-chloroperbenzoic acid and stir for 2 hours, first at, then at room temperature. The reaction mixture is poured into ice-water, and the resulting 4,5-di- (p-methoxyphenyl) -2fii-benzenesulfonyl-hydroxyethylsulfonylimidazole is dried to dryness, then dissolved in SOO ml and stirred for 60 hours. After treatment in the same manner as Example 10, 5- 6-di- (p-methoxyphenyl) -2, 3-dihydro-imidazo 2,1-b thiazole sulfone with m.p. 186-187 ° C.
    Example 10: 25 mol mol of 4- (pmethoxyphenyl) -5 - (4-pyridyl) - y-mercapto-imidazole is suspended in 200 ml of dimethylformamide, and 26 mol of sodium hydride is added and then stirred for 30 minutes at room temperature. After that 25 moles of 1-bromo-2-chloroethane are added, stirred overnight by passing an inert gas, then 20 moles of potassium carbonate are added, heated under reflux, cooled, 600 ml of ice-water is added, decanted from precipitates and washed thoroughly with water. A crude 5 (6) - (p-methoxyphenyl; -6 (5) - (4-pyridyl) -2,3-dihydroimidaeo 2 t Cr-b thiazole is obtained. The crude product is dissolved in warm isopropanol and slowly cooled. The precipitated crystals are collected and recrystallized
    权利要求:
    Claims (2)
    [1]
    1, the 3-diazacyclopent-2-ene ring of which may have an additional ring. the double bond, Ar ^ and A Gd, independently of one another, means unsubstituted 20 or substituted with a lower alkoxy group by lower alkyl or halogen phenyl or unsubstituted pyridyl; n = Q, 1 or
    [2]
    2, Aik is lower alkylene with 2-4 carbon atoms, which separates the nitrogen atom 25 from the sulfur atom by two to four carbon atoms, provided that at least one of the residues Ar and Arg. do not mean phenyl, if n = 0 and 1, the 3-diazacyclopent-2-ene ring means an imidazole ring, or their salts, in the form of a mixture of isomers or individual isomers, characterized in that the compound of the general formula and where Ar ,, Ar ^, η and Aik have the indicated meanings;
    The X-reactive ester esterified into the ester is cyclized in a low-boiling organic solvent in the presence of a base, and the final product is separated free or as a salt and / or as a mixture of isomers or as separate isomers.
    类似技术:
    公开号 | 公开日 | 专利标题
    SU873886A3|1981-10-15|Method of preparing derivatives of amidazo | thiazole or their salts in form of mixture of isomers or individual isomers
    KR850000891B1|1985-06-26|Process for preparing trisubstituted imidazole derivatives
    US4603204A|1986-07-29|Theophylline derivatives
    HU191301B|1987-02-27|Process for preparing 1-/hydroxy-methyl/-1,6,7,11b-tetrahydro-2h,4h-/1,3/-oxazino- or -thiazino/4,3-a/isoquinoline -derivatives
    SU481155A3|1975-08-15|Production method - | morphinans
    US4697020A|1987-09-29|Derivatives of 2,4-thiazolidinedione
    SU1287752A3|1987-01-30|Method of producing imidazo | pyrimidines or their additive salts with acids
    CZ2001434A3|2001-08-15|Process for preparing quinolizin-3-one derivatives
    SU591149A3|1978-01-30|Method of preparing derivatives of triazoloisoquinoline
    US3235555A|1966-02-15|7-amino-3-cyanoethyl-1-methyl-2, 4-dioxo-1, 2, 3, 4, 5, 6-hexahydropyrido[2, 3-d] pyrimidine and related compounds
    FR2496666A1|1982-06-25|NOVEL CEPHALOSPORINE DERIVATIVES AND PHARMACEUTICAL COMPOSITION CONTAINING SAME
    SU1227111A3|1986-04-23|Method of producing guanidine derivatives or their tautomeric compounds or their salts
    FR2634207A1|1990-01-19|[|methyl]benzazepine derivatives, their preparation and their application in therapeutics
    SU797580A3|1981-01-15|Method of preparing isoquinoline derivatives, their salts, racemates or optical isomers
    CA1192188A|1985-08-20|Antihypertensive lactams
    CS199711B2|1980-07-31|Method of producing 1-/n-acylcarbamoyl/-2-cyanaziridines
    US3686178A|1972-08-22|Preparation of 4-aryl-2|-quinazolinones and thiones
    FI88292B|1993-01-15|FRAME STARTING FOR N- | FORMAMIDER
    FR2639944A1|1990-06-08|NOVEL INDOLE DERIVATIVES, PROCESS FOR PREPARING THEM AND PHARMACEUTICAL COMPOSITIONS CONTAINING SAME
    US4549019A|1985-10-22|Pyrimidinecarbamate derivatives as intermediates
    FR2692578A1|1993-12-24|Indolizine derivatives, process for their preparation and use for the preparation of pharmacologically active aminoalkoxybenzenesulfonylindolizine compounds
    US4202977A|1980-05-13|S-Triazolo [1,5-a] pyridine derivatives
    US3882229A|1975-05-06|Composition and method for shrinking mucous membranes
    SU920056A1|1982-04-15|Method of producing r,s-2,3,5,6-tetrahydro-6-phenilimidazo|-thiazole
    Ding et al.1997|Trithia‐and dithiaselenapentalenes from benzylidene‐1, 2‐dithioles and heterocumulenes
    同族专利:
    公开号 | 公开日
    ES471458A1|1979-10-01|
    DD145538A5|1980-12-17|
    AR222309A1|1981-05-15|
    LU77703A1|1979-03-26|
    ES484327A1|1980-05-16|
    EP0000353A2|1979-01-24|
    PL208253A1|1979-06-04|
    AR224381A1|1981-11-30|
    FI782132A|1979-01-08|
    PL116596B1|1981-06-30|
    EP0019688A1|1980-12-10|
    DK305578A|1979-01-08|
    ZA783898B|1979-07-25|
    PT68246A|1978-08-01|
    SU873887A3|1981-10-15|
    AU3778878A|1980-01-10|
    EP0020858A1|1981-01-07|
    IT8149647D0|1981-11-06|
    ES484033A1|1980-04-16|
    GR64978B|1980-06-11|
    DD138212A5|1979-10-17|
    IL55086D0|1978-09-29|
    SU850007A3|1981-07-23|
    NZ187789A|1981-03-16|
    NO782357L|1979-01-09|
    EP0000353A3|1979-06-13|
    SU893134A3|1981-12-23|
    ES478296A1|1979-05-16|
    JPS5416470A|1979-02-07|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US2981739A|1958-01-27|1961-04-25|Diamond Alkali Co|Certain alpha-haloaldehyde addition products of ethylenethioureas and process|
    FR4705M|1964-05-11|
    US3297708A|1965-10-06|1967-01-10|American Cyanamid Co|Method of preparing thiazolidines|
    US3455924A|1967-02-08|1969-07-15|Upjohn Co|Dianisylimidazoles|
    NL164285C|1968-01-09|1980-12-15|Rhone Poulenc Sa|PROCESS FOR THE PREPARATION OF A PHARMACEUTICAL PREPARATION CONTAINING AN IMIDAZOŸ2.1-BŸTHIAZOLE DERIVATIVE, THE PREPARED PHARMACEUTICAL PREPARATIONS AND A METHOD FOR PREPARING THIS IMIDAZOŸ2.1-BŸTHIAZOLDER|
    BE788792A|1971-09-30|1973-03-13|Ici Ltd|METHODS AND COMPOSITIONS FOR ANTI-BACTERIAL USE|
    US3842097A|1973-01-22|1974-10-15|Searle & Co|2-imidazoles and congeners|
    SE428686B|1975-08-11|1983-07-18|Du Pont|PROCEDURE FOR PREPARING ANTI-INFLAMMATORALLY ACTIVE IMIDAZOLS|
    GB1541321A|1976-03-10|1979-02-28|Metabio|2,3-dihydroimidazothiazole derivatives and process for their preparation|
    US4064260A|1976-07-29|1977-12-20|E. I. Du Pont De Nemours And Company|Anti-inflammatory diarylimidazothiazoles and their corresponding S-oxides|
    US4263311A|1976-09-27|1981-04-21|Smithkline Corporation|5,6-Phenyl-2,3-dihydroimidazo [2,1-b] thiazoles|CY1302A|1978-04-11|1985-12-06|Ciba Geigy Ag|Mercapto-imidazole derivatives,their preparation,their pharmaceutical compositions and applications|
    DE2823197A1|1978-05-24|1979-11-29|Schering Ag|NEW IMIDAZOLE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND PHARMACEUTICAL PREPARATIONS CONTAINING THEM|
    US4175127A|1978-09-27|1979-11-20|Smithkline Corporation|Pyridyl substituted 2,3-dihydroimidazo[2,1-b]thiazoles|
    FI800005A|1979-01-05|1980-07-06|Ciba Geigy Ag|FRAMEWORK FOR BICYCLING THREAD SALES|
    US4636516A|1981-02-19|1987-01-13|Yamanouchi Pharmaceutical Co., Ltd.|3,5-di-tert-butyl-4-hydroxyphenyl-substituted heterocyclic compounds|
    IL78834A|1985-05-23|1992-07-15|Smithkline Beckman Corp|2,3-dihydro-5--6-phenylimidazothiazoles and 6,7-dihydro-3--2-phenyl-5h-imidazothiazines and their use as intermediates in a process for preparing the corresponding pyridyl-substituted imidazothiazoles and 5h-imidazothiazines|
    US4803279A|1985-05-23|1989-02-07|Smithkline Beckman Corporation|1.4-dihydro-4-pyridyl-substituted imidazothiazoles and the corresponding thiazines.|
    US5008390A|1985-05-23|1991-04-16|Smithkline Beckman Corporation|Compounds for preparing 6-phenyl-2,3-dihydroimidazo[2,1-b]-thiazoles and corresponding thiazines|
    ZW24186A1|1985-12-12|1987-07-08|Smithkline Beckman Corp|Inhibition of the 5-lipoxygenase pathway|
    US4719218A|1985-12-12|1988-01-12|Smithkline Beckman Corporation|Pyrrolo[1,2-a]imidazole and pyrrolo[1,2-a]pyridine derivatives and their use as 5-lipoxygenase pathway inhibitor|
    AU6355190A|1989-06-13|1991-01-17|Smithkline Beecham Corporation|Inhibition of interleukin-1 and tumor necrosis factor production by monocytes and/or macrophages|
    GB9005966D0|1990-03-16|1990-05-09|May & Baker Ltd|New compositions of matter|
    GB9019838D0|1990-09-11|1990-10-24|Smith Kline French Lab|Compounds|
    US5240918A|1992-03-24|1993-08-31|Egis Gyogyszergyar|2--thiazolidines and process for the preparation thereof|
    US5552422A|1995-01-11|1996-09-03|Merck Frosst Canada, Inc.|Aryl substituted 5,5 fused aromatic nitrogen compounds as anti-inflammatory agents|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    LU77703A|LU77703A1|1977-07-07|1977-07-07|METHOD FOR PRODUCING BICYCLIC THIA-DIAZA COMPOUNDS|
    [返回顶部]