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US 5,965,589 AGranted
Thiazolidinedione derivatives, their production and use
AssigneeTakeda Chemical Industries, Ltd.
InventorsTakashi Sohda, Hiroyuki Odaka, Yu Momose
Life of this patent
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Abstract
A 2,4-thiazolidinedione derivative of the formula (I): ##STR1## wherein R is an optionally substituted hydrocarbon group or heterocyclic group which may be attached through a hydrocarbon chain; n is 0 or 1; X is CH or N; Y is a bivalent hydrocarbon group; R.sup.1 and R.sup.2 are the same or different and are a hydrogen atom, a halogen atom, an optionally substituted hydroxyl group or an optionally substituted hydrocarbon group, and either R.sup.1 or R.sup.2 and a part of Y may be linked together to form a ring; and L and M are a hydrogen atom, or L and M are linked together to form a bond; or a salt thereof. A pharmaceutical composition comprising the compound (I) and a process for producing the compound (I) are also provided.
Claims12
A 2,4-thiazolidinedione derivative of the formula (I):
- ##STR58## wherein:
- R is a 1,3-oxazolyl which may be attached through a hydrocarbon chain having 1 to 8 carbon atoms selected from an alkylene group, an alkenylene group, an alkadienylene group or an alkatrienylene group and optionally having at least one substituent selected from:
- (a) a C.sub.1-8 aliphatic hydrocarbon group selected from an alkyl group, an alkenyl group or an alkynyl group;
- (b) a C.sub.3-7 alicyclic hydrocarbon group selected from a cycloalkyl group or a cycloalkenyl group;
- (c) a C.sub.4-9 alicyclic-aliphatic hydrocarbon group selected from a cycloalkyl-alkyl group or a cycloalkenyl-alkyl group;
- (d) a C.sub.7-9 phenylalkyl, a C.sub.11-13 naphthylalkyl or 2-phenylethenyl;
- (e) an aromatic hydrocarbon group selected from phenyl or naphthyl;
- (f) an amino group;
- (g) a N-monosubstituted amino group having a substituent selected from (1) a C.sub.1-4 alkyl group, (2) a C.sub.3-7 cycloalkyl group, (3) an aryl group selected from phenyl or naphthyl, (4) an aralkyl group selected from benzyl or phenethyl, (5) an acyl group selected from acetyl or propionyl, (6) a carbamoyl group, (7) N-monosubstituted carbamoyl group selected from N-methylcarbamoyl, N-ethylcarbamoyl or N-propylcarbamoyl, (8) N,N-disubstituted carbamoyl group selected from N,N-dimethylcarbamoyl, N-methyl-N-ethylcarbamoyl or N,N-diethylcarbamoyl, (9) a C.sub.2-5 alkoxycarbonyl group, (10) a hydroxy group, (11) a C.sub.1-4 alkoxy group or (12) an aralkyloxy group selected from benzyloxy, phenethyloxy or naphthyl-methyloxy;
- or
- (h) a N,N-disubstituted amino group having a first substituent selected from groups (1) to (12) defined above with respect to the N-monosubstituted amino group, and having a second substituent selected from (13) a C.sub.1-4 alkyl group, (14) a C.sub.3-7 cycloalkyl group, (15) an aryl group selected from phenyl or naphthyl or (16) an aralkyl group selected from benzyl or phenethyl, wherein the first and second substituents may be linked together with the nitrogen atom to form a cyclic amino group;
- wherein groups (b) and (c) may be substituted by 1 to 3 C.sub.1-4 alkyl groups;
- and wherein groups (d) and (e) may have 1 to 4 substituents selected from halogen, hydroxy, cyano, nitro, trifluoromethyl, C.sub.1-4 alkoxy, C.sub.1-4 alkyl, C.sub.2-5 alkoxycarbonyl, C.sub.1-3 alkylthio or C.sub.1-4 alkylamino;
- n is 1;
- X is CH;
- Y is a C.sub.2-7 alkylene group;
- R.sup.1 is a hydroxy group, a C.sub.1-4 alkoxy group, an aralkyloxy group selected from benzyloxy, phenethyloxy or naphthylmethyloxy, or an optionally substituted hydrocarbon group selected from:
- (i) a C.sub.1-8 aliphatic hydrocarbon group selected from an alkyl group, an alkenyl group or an alkynyl group;
- (ii) a C.sub.3-7 alicyclic hydrocarbon group selected from a cycloalkyl group or a cycloalkenyl group;
- (iii) a C.sub.4-9 alicyclic-alihatic hydrocarbon group selected from a cycloalkyl-alkyl group or a cycloalkenyl-alkyl group:
- (iv) a C.sub.7-9 phenylalkyl, a C.sub.11-13 naphthyalkyl or 2-phenylethenyl;
- or
- (v) an aromatic hydrocarbon group selected from phenyl or naphthyl;
- wherein groups (ii) and (iii) may be substituted by 1 to 3 C.sub.1-4 alkyl groups, and wherein groups (iv) and (v) may have 1 to 4 substituents selected from halogen, hydroxy, cyano, nitro, trifluoromethyl, C.sub.1-4 alkoxy, C.sub.1-4 alkyl, C.sub.2-4 alkoxycarbonyl, C.sub.1-3 alkylthio or C.sub.1-4 alkylamino;
- R.sup.2 is a hydrogen atom, a halogen atom, a hydroxy group, a C.sub.1-4 alkoxy group, an aralkyloxy group selected from benzyloxy, phenethyloxy or naphthylmethyloxy, or an optionally substituted hydrocarbon group selected from:
- (i) a C.sub.1-8 aliphatic hydrocarbon group selected from an alkyl group, an alkenyl group, or an alkynyl group;
- (ii) a C.sub.3-7 alicyclic hydrocarbon group selected from a cycloalkyl group or a cycloalkenyl group;
- (iii) a C.sub.4-9 alicyclic-aliphatic hydrocarbon group selected from a cycloalkyl-alkyl group or a cycloalkenyl-alkyl group;
- (iv) a C.sub.7-9 phenylalkyl, a C.sub.11-13 naphthylalkyl or 2-phenylethenyl;
- or
- (v) an aromatic hydrocarbon group selected from phenyl or naphthyl;
- wherein groups (ii) and (iii) may be substituted by 1 to 3 C.sub.1-4 alkyl groups, and wherein groups (iv) and (v) may have 1 to 4 substituents selected from halogen, hydroxy, cyano, nitro, trifluoromethyl, C.sub.1-4 alkoxy, C.sub.1-4 alkyl, C.sub.2-4 alkoxycarbonyl, C.sub.1-3 alkylthio or C.sub.1-4 alkylamino;
- and
- wherein either R.sup.1 or R.sup.2 and one carbon atom of Y may be linked together to form a ring;
- provided that ##STR59## is other than ##STR60## and L and M are each a hydrogen atom, or L and M are linked together to form a bond;
- or a salt thereof.
33 more elements
A pharmaceutical composition which comprises an effective amount of a 2,4-thiazolidinedione derivative of the formula (I):
- ##STR63## wherein:
- R is a 1,3-oxazolyl which may be attached through a hydrocarbon chain having 1 to 8 carbon atoms selected from an alkylene group, an alkenylene group, an alkadienylene group or an alkatrienylene group and optionally having at least one substituent selected from:
- (a) a C.sub.1-8 aliphatic hydrocarbon group selected from an alkyl group, an alkenyl group or an alkynyl group;
- (b) a C.sub.3-7 alicyclic hydrocarbon group selected from a cycloalkyl group or a cycloalkenyl group;
- (c) a C.sub.4-9 alicyclic-aliphatic hydrocarbon group selected from a cycloalkyl-alkyl group or a cycloalkenyl-alkyl group;
- (d) a C.sub.7-9 phenylalkyl, a C.sub.11-13 naphthylalkyl or 2-phenylethenyl;
- (e) an aromatic hydrocarbon group selected from phenyl or naphthyl;
- (f) an amino group;
- (g) a N-monosubstituted amino group having a substituent selected from (1) a C.sub.1-4 alkyl group, (2) a C.sub.3-7 cycloalkyl group, (3) an aryl group selected from phenyl or naphthyl, (4) an aralkyl group selected from benzyl or phenethyl, (5) an acyl group selected from acetyl or propionyl, (6) a carbamoyl group, (7) N-monosubstituted carbamoyl group selected from N-methylcarbamoyl, N-ethylcarbamoyl or N-propylcarbamoyl, (8) N,N-disubstituted carbamoyl group selected from N,N-dimethylcarbamoyl, N-methyl-N-ethylcarbamoyl or N,N-diethylcarbamoyl, (9) a C.sub.2-5 alkoxycarbonyl group, (10) a hydroxy group, (11) a C.sub.1-4 alkoxy group or (12) an aralkyloxy group selected from benzyloxy, phenethyloxy or naphthylmethyloxy;
- or
- (h) a N,N-disubstituted amino group having a first substituent selected from groups (1) to (12) defined above with respect to the N-monosubstituted amino group, and having a second substituent selected from (13) a C.sub.1-4 alkyl group, (14) a C.sub.3-7 cycloalkyl group, (15) an aryl group selected from phenyl or naphthyl or (16) an aralkyl group selected from benzyl or phenethyl, wherein the first and second substituents may be linked together with the nitrogen atom to form a cyclic amino group;
- wherein groups (b) and (c) may be substituted by 1 to 3 C.sub.1-4 alkyl groups;
- and wherein groups (d) and (e) may have 1 to 4 substituents selected from halogen, hydroxy, cyano, nitro, trifluoromethyl, C.sub.1-4 alkoxy, C.sub.1-4 alkyl, C.sub.2-4 alkoxycarbonyl, C.sub.1-3 alkylthio or C.sub.1-4 alkylamino;
- n is 1;
- X is CH;
- Y is a C.sub.2-7 alkylene group;
- R.sup.1 is a hydroxy group, a C.sub.1-4 alkoxy group, an aralkyloxy group selected from benzyloxy, phenethyloxy or naplithylmethyloxy, or an optionally substituted hydrocarbon group selected from:
- (i) a C.sub.1-8 aliphatic hydrocarbon group selected from an alkyl group, an alkenyl group or an alkynyl group;
- (ii) a C.sub.3-7 alicyclic hydrocarbon group selected from a cycloalkyl group or a cycloalkenyl group:
- (iii) a C.sub.4-9 alicyclic-aliphatic hydrocarbon group selected from a cycloalkyl-alkyl group or a cycloalkenyl-alkyl group;
- (iv) a C.sub.7-9 phenylalkyl, a C.sub.11-13 naphthylalkyl or 2-phenylethenyl;
- or
- (v) an aromatic hydrocarbon group selected from phenyl or naphthyl;
- wherein groups (ii) and (iii) may be substituted by 1 to 3 C.sub.1-4 alkyl groups, and wherein groups (iv) and (v) may have 1 to 4 substituents selected from halogen, hydroxy, cyano, nitro, trifluoromethyl, C.sub.1-4 alkoxy, C.sub.1-4 alkyl, C.sub.2-4 alkoxycarbonyl, C.sub.1-3 alkylthio or C.sub.1-4 alkylamino;
- R.sup.2 is a hydrogen atom, a halogen atom, a hydroxy group, a C.sub.1-4 alkoxy group, an aralkyloxy group selected from benzyloxy, phenethyloxy or naphthylmethyloxy, or an optionally substituted hydrocarbon group selected from:
- (i) a C.sub.1-8 aliphatic hydrocarbon group selected from an alkyl group, an alkenyl group, or an alkynyl group;
- (ii) a C.sub.3-7 alicyclic hydrocarbon group selected from a cycloalkyl group or a cycloalkenyl group;
- (iii) a C.sub.4-9 alicyclic-aliphatic hydrocarbon group selected from a cycloalkylalkyl group or a cycloalkenyl-alkyl group;
- (iv) a C.sub.7-9 phenylalkyl, a C.sub.11-13 naphthylalkyl or 2-phenylethenyl;
- or
- (v) an aromatic hydrocarbon group selected from phenyl or naphthyl;
- wherein groups (ii) and (iii) may be substituted by 1 to 3 C.sub.1-4 alkyl groups, and wherein groups (iv) and (v) may have 1 to 4 substituents selected from halogen, hydroxy, cyano, nitro, trifluoromethyl, C.sub.1-4 alkoxy, C.sub.1-4 alkyl, C.sub.2-4 alkoxycarbonyl, C.sub.1-3 alkylthio or C.sub.1-4 alkylamino;
- and
- wherein either R.sup.1 or R.sup.2 and one carbon atom of Y may be linked together to form a ring;
- provided that ##STR64## is other than ##STR65## and L and M are each a hydrogen atom, or L and M are linked together to form a bond;
- or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
33 more elements
Dependencies are inferred from the claim text.