公开(公告)号：US3795681A

公开(公告)日：1974-03-05

申请号：US3795681D

申请日：1972-05-26

Applicant: HOECHST AG

Inventor： RUSCHIG H ,  MEIXNER W ,  ALPERMANN H

IPC: C07D333/38 ,  A61K27/00 ,  C07D63/16

CPC classification number: C07D333/38 ,  Y10S514/916

Abstract: NOVEL AMINOTHIOPHENE-CARBOXYLIC ACID ESTERS ARE DESCRIBED AS WELL AS A PROCESS FOR THEIR MANUFACTURE AND THEIR ANTIPHLOGISTIC AND ANTIPYRETIC ACTION. THE NOVEL COMPOUNDS CORRESPOND TO THE FORMULA I

2-R1,3-(R-NH-),4-(R4-COO-CH(-R3)-OOC-),5-R2-THIOPHENE

WHEREIN R REPRESENTS PHENYL WHICH MAY CARRY 1, 2 OR 3 SUBSTITUENTS SELECTED FROM HALOGEN, TRIFLUOROMETHYL, LOW MOLECULAR ALKYL AND ALKOXY, ARALKOXY BEING LOW MOLECULAR IN THE ALKYLENE MOIETY, AND CYCLOALKYL HAVING 5-6 MEMBERS, AND WHEREIN TWO VICINAL SUBSTITUENTS MAY BE MEMBERS OF A CONDENSED ALICYCLIC RING SYSTEM, AND WHEREIN R1 AND R2 EACH REPRESENTS HYDROGEN OR LOW MOLECULAR ALKYL, R3 REPRESENTS HYDROGEN OR LOW MOLECULAR ALKYL AND R4 REPRESENTS ALKYL OR ARYL IN WHICH CASE THE ARYL GROUP MAY CONTAIN 1 OR 2 HETERO ATOMS, SUCH AS NITROGEN, OXYGEN OR SULFUR.

公开(公告)号：ZA7203614B

公开(公告)日：1973-03-28

申请号：ZA7203614

申请日：1972-05-26

Applicant: HOECHST AG

Inventor： RUSCHIG H ,  MEIXNER W ,  ALPERMANN H

IPC: C07D333/38

CPC classification number: C07D333/38 ,  Y10S514/916

公开(公告)号：NO118669B

公开(公告)日：1970-01-26

申请号：NO16250766

申请日：1966-04-06

Applicant: HOECHST AG

Inventor： RUSCHIG H ,  MEIXNER W ,  ALPERMANN H

IPC: A61K31/38 ,  C07D333/38

Abstract: 1,133,850. Aminothiophene derivatives. FARBWERKE HOECHST A.G. 12 April, 1966 [10 April, 1965], No. 15940/66. Heading C2C. Novel aminothiophene derivatives have the formula where R is a phenyl radical containing one or more substituents which may be a halogen atom, CF 3 , C 1-4 alkyl or C 1-4 alkoxy, phenyl-C 1-4 alkoxy which may be substituted in the phenyl ring by halo, C 1-4 alkyl or C 1-4 alkoxy, and C 5-6 cycloalkyl, or R may represent a tetrahydronaphthalene or indane radical; R 1 is a carboxylic, carbonamide, or carboxylic ester group containing in the ester group (a) an alkyl, dialkyl - amino - alkyl, or alkylene - iminoalkyl radical having 4-5 ring carbons which may be interrupted by O or where each alkyl is C 1-4 ; or (b) a phenyl radical which may be substituted by halo, C 1-4 alkyl or C 1-4 alkoxy; or (c) a phenyl-C 1-4 alkyl radical; and R 2 and R 3 each represents H or C 1-4 alkyl. The novel compounds may be obtained: (1) by condensing a compound of formula where R 4 = R 1 or CN, with R-NH 2 to yield a 3 - amino - 2,5 - dihydrothiophene which is dehydrogenated by known methods and if R 4 = CN it is converted to R 1 ; (2) by condensing a compound of formula with RY, where one of X or Y is amino and the other a halogen atom, and if necessary dehydrogenating and converting R 4 to R 1 ; (3) by de-acylating a compound corresponding to (I) (which may be partially or completely hydrogenated) having an acyl group in place of the H attached to the N atom, and optionally dehydrogenating the product and converting R 4 to R 1 . 4-Cyano-thiophanone is obtained introducing a mixture of acrylonitrile and thioglycolic acid methyl ester into fresh sodium methylate. and refluxing. 3 - (R - substituted - anilino) - 4 - cyano - 2,5- dihydrothiophenea are obtained by reacting 4- cyanothiophane with an R-substituted aniline. 3 - (R - substituted - anilino) - 4 - cyano - thiophenes are obtained by dehydrogenation of the corresponding 2,5-dihydrothiophenes by boiling with tetrachloroquinone. Pharmaceutical compositions having antiphlogistic and anti-pyretic properties comprise compounds of Formula I together with a pharmaceutically suitable carrier in forms such as tablets, dragees, solutions, suppositories, ointments and powders.

公开(公告)号：ZA723614B

公开(公告)日：1973-03-28

申请号：ZA723614

申请日：1972-05-26

Applicant: HOECHST AG

Inventor： RUSCHIG H ,  MEIXNER W ,  ALPERMANN H

IPC: C07D333/38

公开(公告)号：SE316489B

公开(公告)日：1969-10-27

申请号：SE466666

申请日：1966-04-06

Applicant: HOECHST AG

Inventor： ALPERMANN H ,  RUSCHIG H ,  MEIXNER W

IPC: A61K31/38 ,  C07D333/38 ,  C07D63/16

Abstract: 1,133,850. Aminothiophene derivatives. FARBWERKE HOECHST A.G. 12 April, 1966 [10 April, 1965], No. 15940/66. Heading C2C. Novel aminothiophene derivatives have the formula where R is a phenyl radical containing one or more substituents which may be a halogen atom, CF 3 , C 1-4 alkyl or C 1-4 alkoxy, phenyl-C 1-4 alkoxy which may be substituted in the phenyl ring by halo, C 1-4 alkyl or C 1-4 alkoxy, and C 5-6 cycloalkyl, or R may represent a tetrahydronaphthalene or indane radical; R 1 is a carboxylic, carbonamide, or carboxylic ester group containing in the ester group (a) an alkyl, dialkyl - amino - alkyl, or alkylene - iminoalkyl radical having 4-5 ring carbons which may be interrupted by O or where each alkyl is C 1-4 ; or (b) a phenyl radical which may be substituted by halo, C 1-4 alkyl or C 1-4 alkoxy; or (c) a phenyl-C 1-4 alkyl radical; and R 2 and R 3 each represents H or C 1-4 alkyl. The novel compounds may be obtained: (1) by condensing a compound of formula where R 4 = R 1 or CN, with R-NH 2 to yield a 3 - amino - 2,5 - dihydrothiophene which is dehydrogenated by known methods and if R 4 = CN it is converted to R 1 ; (2) by condensing a compound of formula with RY, where one of X or Y is amino and the other a halogen atom, and if necessary dehydrogenating and converting R 4 to R 1 ; (3) by de-acylating a compound corresponding to (I) (which may be partially or completely hydrogenated) having an acyl group in place of the H attached to the N atom, and optionally dehydrogenating the product and converting R 4 to R 1 . 4-Cyano-thiophanone is obtained introducing a mixture of acrylonitrile and thioglycolic acid methyl ester into fresh sodium methylate. and refluxing. 3 - (R - substituted - anilino) - 4 - cyano - 2,5- dihydrothiophenea are obtained by reacting 4- cyanothiophane with an R-substituted aniline. 3 - (R - substituted - anilino) - 4 - cyano - thiophenes are obtained by dehydrogenation of the corresponding 2,5-dihydrothiophenes by boiling with tetrachloroquinone. Pharmaceutical compositions having antiphlogistic and anti-pyretic properties comprise compounds of Formula I together with a pharmaceutically suitable carrier in forms such as tablets, dragees, solutions, suppositories, ointments and powders.