Azolidinone-vinyl fused-benzene derivatives
View Patent ↗The present invention is related to azolidinedione-vinyl fused-benzene derivatives of formula (I) for the treatment and/or prophylaxis of autoimmune disorders and/or inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, bacterial or viral infections, kidney diseases, platelet aggregation, cancer, graft rejection or lung injuries. Formula (I), wherein A, X, Y, Z, R 1 , R 2 and n are as described in the description.
1. A method for the treatment of inflammation, the method comprising, administering to a subject in need thereof, an effective amount of a compound of formula (I):
as well as its geometrical isomers, its optically active forms as enantiomers, diastereomers and its racemate forms, as well as pharmaceutically acceptable salts thereof, wherein
A is a 5-8 membered heterocyclic group;
X is S or O;
Y 1 and Y 2 are independently S or O;
Z is S or O;
R′ is H, CN, carboxy, acyl, C 1 -C 6 -alkoxy, halogen, hydroxy, acyloxy, C 1 -C 6 -alkyl carboxy, C 1 -C 6 -alkyl acyloxy, C 1 -C 6 -alkyl alkoxy, alkoxycarbonyl, C 1 -C 6 -alkyl alkoxycarbonyl, aminocarbonyl, C 1 -C 6 -alkyl aminocarbonyl, acylamino, C 1 C 6 -alkyl acylamino, ureido, C 1 -C 6 -alkyl ureido, amino, C 1 -C 6 -alkyl amino, ammonium, sulfonyloxy, C 1 -C 6 -alkyl sulfonyloxy, sulfonyl, C 1 -C 6 -alkyl sulfonyl, sulfinyl, C 1 -C 6 -alkyl sulfinyl, sulfanyl, C 1 -C 6 -alkyl sulfanyl, sulfonylamino, C 1 -C 6 -alkyl sulfonylamino or carbamate;
R 2 is selected from the group consisting of H, halogen, acyl, amino, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -alkyl carboxy, C 1 -C 6 -alkyl acyl, C 1 -C 6 -alkyl alkoxycarbonyl, C 1 -C 6 -alkyl aminocarbonyl, C 1 -C 6 -alkyl acyloxy, C 1 -C 6 -alkyl acylamino, C 1 -C 6 -alkyl ureido, C 1 -C 6 -alkyl amino, C 1 -C 6 -alkyl alkoxy, C 1 -C 6 -alkyl sulfanyl, C 1 -C 6 -alkyl sulfinyl, C 1 -C 6 -alkyl sulfonyl, C 1 -C 6 -alkyl sulfonylaminoaryl, aryl, C 3 -C 8 -cycloalkyl or heterocycloalkyl, C 1 -C 6 -alkyl aryl, C 2 -C 6 -alkenyl-aryl, C 2 -C 6 -alkynyl aryl, carboxy, cyano, hydroxy, C 1 -C 6 -alkoxy, nitro, acylamino, ureido, C 1 -C 6 -alkyl carbamate, sulfonylamino, sulfanyl, or sulfonyl;
n is 0, 1 or 2;
with the proviso that the following compounds are excluded:
wherein R 1 is a lower alkyl or aralkyl and R 2 is H or a halogen.
2. The method according to claim 1 , wherein Y 1 and Y 2 are both oxygen.
3. The method according to claim 1 , wherein n is 1 or 2 and R 1 and R 2 are both H.
4. The method according to claim 1 , wherein, in the compound of formula (I), X is S, Y 1 and Y 2 are both O, and n is 0.
5. The method according to claim 1 , whereby the compound of formula (I) is a thiazolidinone-vinyl fused-benzene of the formula (Ia)
wherein Y 1 , R 1 , R 2 , Z and n are as above defined for the compound of formula (I);
V and W are each, independently from each other, O, S or —NR 3 wherein R 3 is H or C 1 -C 6 alkyl;
G is a C 1 -C 5 alkylene or a C 1 -C 5 alkenylene group;
o and m are each, independently from each other, 0 or 1; and
q is an integer from 0 to 4.
6. The method according to claim 5 , whereby the thiazolidinone-vinyl fused-benzene has the formula (Ib):
wherein Y 1 , R 1 , R 2 , V, Z, W, m, n, o, q are as above defined in the compound of formula (Ia), and p is an integer from 1 to 4.
7. The method according to claim 5 , whereby the thiazolidinone-vinyl fused-benzene has the formula (Ic):
wherein W, as well as R 1 and Y 1 , are as above defined in the compound of formula (Ia).
8. The method according to claim 5 , whereby the thiazolidinone-vinyl fused-benzene has the formula (Id):
wherein R 1 , R 2 , Z and n are as above defined in formula (Ia); o is 0 or 1;
p is an integer from 1 to 4 and q is an integer from 0 to 4.
9. The method according to claim 5 , wherein, in formula (Ia), Z is O, m is 0, n is 1, p is 1 or 2, q is 1, and R 1 and R 2 are each as above defined for the compound of formula (Ia).
10. The method according to claim 5 , wherein, in formula (Ia), m is 1, n is 0, p is 1 or 2, q is 0, and R 1 and R 2 are each as above defined for the compound of formula (Ia).
11. The method according to claim 5 , wherein, in formula (Ia), m is 0, n is 1, p is 1 or 2, q is 0, and R 1 and R 2 are each as defined above for the compound of formula (I).
12. The method according to claim 5 , wherein, in formula (Ia), R 1 is halogen or hydrogen.
13. A thiazolidinone-vinyl fused-benzene according to formula (II-a):
wherein A is selected from the group consisting of dioxol, dioxin, dihydrofuran, (dihydro) furanyl, (dihydro)oxazinyl, pyridinyl, isooxazolyl, oxazolyl (dihydro)napthalenyl, pyrimidinyl, triazolyl, imidazolyl, pyrazinyl, thiazolidinyl, thiadiazolyl, and oxadiazolyl;
R 2 is selected from the group consisting of H, halogen, acyl, amino, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkenyl, C 1 -C 6 -alkyl carboxy, C 1 -C o -alkyl acyl, C 1 -C 6 -alkyl alkoxycarbonyl, C 1 -C 6 -alkyl aminocarbonyl, C 1 -C o -alkyl acyloxy, C 1 -C 6 -alkyl acylamino, C 1 -C 6 -alkyl ureido, C 1 -C 6 -alkyl carbamate, C 1 -C 6 -alkyl amino, C 1 -C 6 -alkyl alkoxy, C 1 -C 6 -alkyl sulfanyl, C 1 -C 6 -alkyl sulfinyl, C 1 -C 6 -alkyl sulfonyl, C 1 -C 6 -alkyl sulfonylaminoaryl, aryl, C 3 -C 8 -cycloalkyl or heterocycloalkyl, C 1 -C 6 -alkyl aryl, C 2 -C 6 -alkenyl-aryl, C 2 -C 6 -alkynyl aryl, carboxy, cyano, hydroxy, C 1 -C 6 -alkoxy, nitro, acylamino, ureido, sulfonylamino, sulfanyl, and sulfonyl.
14. A thiazolidinone-vinyl fused-benzene according to formula (II):
as well as its geometrical isomers, its optically active forms as enantiomers, diastereomers and its racemate forms, as well as pharmaceutically acceptable salts thereof, wherein
Y 1 is S or O;
Z is S or O;
R 1 is H, CN, carboxy, acyl, C 1 -C 6 -alkoxy, halogen, hydroxy, acyloxy, C 1 -C 6 -alkyl carboxy, C 1 -C 6 -alkyl acyloxy, C 1 -C 6 -alkyl alkoxy, alkoxycarbonyl, C 1 -C 6 -alkyl alkoxycarbonyl, aminocarbonyl, C 1 -C 6 -alkyl aminocarbonyl, acylamino, C 1 -C 6 -alkyl acylamino, ureido, C 1 -C 6 -alkyl ureido, amino, C 1 -C 6 -alkyl amino, ammonium, sulfonyloxy, C 1 -C 6 -alkyl sulfonyloxy, sulfonyl, C 1 -C 6 -alkyl sulfonyl, sulfinyl, C 1 -C 6 -alkyl sulfinyl, sulfanyl, C 1 -C 6 -alkyl sulfanyl, sulfonylamino, C 1 -C 6 -alkyl sulfonylamino or carbamate;
R 2 is selected from the group consisting of H, halogen, acyl, amino, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -alkyl carboxy, C 1 -C 6 -alkyl acyl, C 1 -C 6 -alkyl alkoxycarbonyl, C 1 -C 6 -alkyl aminocarbonyl, C 1 -C 6 -alkyl acyloxy, C 1 -C 6 -alkyl acylamino, C 1 -C 6 -alkyl ureido, C 1 -C 6 -alkyl amino, C 1 -C 6 -alkyl alkoxy, C 1 -C 6 -alkyl sulfanyl, C 1 -C 6 -alkyl sulfinyl, C 1 -C 6 -alkyl sulfonyl, C 1 -C 6 -alkyl sulfonylaminoaryl, aryl, C 3 -C 8 -cycloalkyl or heterocycloalkyl, C 1 -C 6 -alkyl aryl, C 2 -C 6 -alkenyl-aryl, C 2 -C 6 -alkynyl aryl, carboxy, cyano, hydroxy, C 1 -C 6 -alkoxy, nitro, acylamino, ureido, C 1 -C 6 -alkyl carbamate, sulfonylamino, sulfanyl, and sulfonyl;
n is 0 or 1.
15. The thiazolidinone-vinyl fused-benzene according to claim 14 , wherein Y 1 is O.
16. The thiazolidinone-vinyl fused-benzene according to claim 14 , wherein R 1 is selected from the group consisting of C 1 -C 6 -alkyl, C 1 -C 6 -alkyl aryl, aryl, C 3 -C 8 -cycloalkyl or heterocycloalkyl, C 1 -C 6 -alkyl aryl, C 2 -C 6 -alkenyl-aryl and C 2 -C 6 -alkynyl aryl.
17. A thiazolidinone-vinyl fused-benzene according to formula (III):
as well as its geometrical isomers, its optically active forms as enantiomers, diastereomers and its racemate forms, as well as pharmaceutically acceptable salts thereof, and wherein
R 1 is H, CN, carboxy, acyl, C 1 -C 6 -alkoxy, halogen, hydroxy, acyloxy, C 1 -C 6 -alkyl carboxy, C 1 -C 6 -alkyl acyloxy, C 1 -C 6 -alkyl alkoxy, alkoxycarbonyl, C 1 -C 6 -alkyl alkoxycarbonyl, aminocarbonyl, C 1 -C 6 -alkyl aminocarbonyl, acylamino, C 1 -C 6 -alkyl acylamino, ureido, C 1 -C 6 -alkyl ureido, amino, C 1 -C 6 -alkyl amino, ammonium, sulfonyloxy, C 1 -C 6 -alkyl sulfonyloxy, sulfonyl, C 1 -C 6 -alkyl sulfonyl, sulfinyl, C 1 -C 6 -alkyl sulfinyl, sulfanyl, C 1 -C 6 -alkyl sulfanyl, sulfonylamino, C 1 -C 6 -alkyl sulfonylamino or carbamate;
R 2 is selected from the group consisting of H, halogen, acyl, amino, C 1 -C 6 -alkyl, C 2 -C o -alkenyl, C 2 -C 6 -alkynyl, C 1 -C o -alkyl carboxy, C 1 -C 6 -alkyl acyl, C 1 -C 6 -alkyl alkoxycarbonyl, C 1 -C 6 -alkyl aminocarbonyl, acyloxy, C 1 -C 6 -alkyl acylamino, C 1 -C 6 -alkyl ureido, C 1 -C 6 -alkyl amino, C 1 -C 6 -alkyl alkoxy, C 1 -C 6 -alkyl sulfanyl, C 1 -C 6 -alkyl sulfinyl, C 1 -C 6 -alkyl sulfonyl, C 1 -C 6 -alkyl sulfonylaminoaryl, aryl, C 3 -C 8 -cycloalkyl or heterocycloalkyl, C 1 -C 6 -alkyl aryl, C 2 -C 6 -alkenyl-aryl, C 2 -C 6 -alkynyl aryl, carboxy, cyano, hydroxy, C 1 -C 6 -alkoxy, nitro, acylamino, ureido, C 1 -C 6 -alkyl carbamate, sulfonylamino, sulfanyl, and sulfonyl.
18. A thiazolidinone-vinyl fused-benzene according any of formulae (IV), (V) and (VI):
wherein R 1 is selected from the group consisting of hydrogen, halogen, cyano, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, acyl, and alkoxy cabonyl, and
R 2 is selected from the group consisting of H, halogen, acyl, amino, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -alkyl carboxy, C 1 -C 6 -alkyl acyl, C 1 -C 6 -alkyl alkoxycarbonyl, C 1 -C 6 -alkyl aminocarbonyl, C 1 -C 6 -alkyl acyloxy, C 1 -C 6 -alkyl acylamino, C 1 -C 6 -alkyl ureido, C 1 -C 6 -alkyl amino, C 1 -C 6 -alkyl alkoxy, C 1 -C 6 -alkyl sulfanyl, C 1 -C 6 -alkyl sulfinyl, C 1 -C 6 -alkyl sulfonyl, C 1 -C 6 -alkyl sulfonylaminoaryl, aryl, C 3 -C 8 -cycloalkyl or heterocycloalkyl, C 1 -C 6 -alkyl aryl, C 2 -C 6 -alkenyl-aryl, C 2 -C 6 -alkynyl aryl, carboxy, cyano, hydroxy, C 1 -C 6 -alkoxy, nitro, acylamino, ureido, C 1 -C 6 -alkyl carbamate, sulfonylamino, sulfanyl, and sulfonyl.
19. The thiazolidinone-vinyl fused-benzene according to claim 13 , selected from the group consisting of:
5-(1,3-benzodioxol-5-ylmethylene)-1,3-thiazolidine-2,4-dione,
5-(1,3-benzodioxol-5-ylmethylene)-2-thioxo-1,3-thiazolidin-4-one,
5-(2,3-dihydro-1,4-benzodioxin-6-ylmethylene)-1,3-thiazolidine-2,4-dione,
5-(2,3-dihydro-1-benzofuran-5-ylmethylene)-1,3-thiazolidine-2,4-dione,
5-[(7-methoxy-1,3-benzodioxol-5-yl)methylene]-1,3-thiazolidine-2,4-dione,
5-[(9,10-dioxo-9,10-dihydroanthracen-2-yl)methylene]-1,3-thiazolidine-2,4-dione,
(5-[(2,2-difluoro-1,3-benzodioxol-5-yl)methylene]-1,3-thiazolidine-2,4-dione,
(5Z)-5-(1,3-dihydro-2-benzofuran-5-ylmethylene)-1,3-thiazolidine-2,4-dione,
5-(1-benzofuran-5-ylmethylene)-1,3-thiazolidine-2,4-dione,
5-[(4-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)methylene]-1,3-thiazolidine-2,4-dione,
5-(1,3-benzodioxol-5-ylmethylene)-2-imino-1,3-thiazolidin-4-one,
5-Quinolin-6-ylmethylene-thiazolidine-2,4-dione,
5-Quinolin-6-ylmethylene-2-thioxo-thiazolidin-4-one,
2-Imino-5-quinolin-6-ylmethylene-thiazolidin-4-one,
5-(3-Methyl-benzo[d]isoxazol-5-ylmethylene)-thiazolidine-2,4-dione,
5-(4-Phenyl-quinazolin-6-ylmethylene)-thiazolidine-2,4-dione,
5-(4-Dimethylamino-quinazolin-6-ylmethylene)-thiazolidine-2,4-dione,
5-[(4-aminoquinazolin-6-yl)methylene]-1,3-thiazolidine-2,4-dione,
5-[(4-piperidin-1-ylquinazolin-6-yl)methylene]-1,3-thiazolidine-2,4-dione,
5-[(4-morpholin-4-ylquinazolin-6-yl)methylene]-1,3-thiazolidine-2,4-dione,
5-{[4-(benzylamino)quinazolin-6-yl]methylene}-1,3-thiazolidine-2,4-dione,
5-{[4-(diethylamino)quinazolin-6-yl]methylene)-1,3-thiazolidine-2,4-dione,
5-({4-[(pyridin-2-ylmethyl)amino]quinazolin-6-yl}methylene)-1,3-thiazolidine-2,4-dione,
5-({4-[(pyridin-3-ylmethyl)amino]quinazolin-6-yl}methylene)-1,3-thiazolidine-2,4-dione,
ethyl 1-{6-[(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]quinazolin-4-yl}piperidine-3-carboxylate,
ethyl 1-{6-[(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]quinazolin-4-yl)piperidine-4-carboxylate,
tert-butyl-1-{6-[(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]quinazolin-4-yl)-L-prolinate,
5-{[4-(4-methylpiperazin-1-yl)quinazolin-6-yl]methylene}-1,3-thiazolidine-2,4-dione,
5-{[4-(4-pyrimidin-2-ylpiperazin-1-yl)quinazolin-6-yl]methylene}-1,3-thiazolidine-2,4-dione,
5-({4-[4-(4-fluorophenyl)piperidin-1-yl]quinazolin-6-yl}methylene)-1,3-thiazolidine-2,4-dione,
5-{[4-(4-benzylpiperidin-1-yl)quinazolin-6-yl]methylene}-1,3-thiazolidine-2,4-dione,
5-({4-[4-(2-phenylethyl)piperidin-1-yl]]quinazolin-6-yl}methylene)-1,3-thiazolidine-2,4-dione,
5-{[4-(4-methylpiperidin-1-yl)quinazolin-6-yl]methylene}-1,3-thiazolidine-2,4-dione,
5-{[4-(4-hydroxypiperidin-1-yl)quinazolin-6-yl]methylene}-1,3-thiazolidine-2,4-dione,
1-[6-(2,4-Dioxo-thiazolidin-5-ylidenemethyl)-quinazolin-4-yl]-piperidine-4-carboxylic acid,
1-[6-(2,4-Dioxo-thiazolidin-5-ylidenemethyl)-quinazolin-4-yl]-piperidine-3-carboxylic acid,
1-[6-(2,4-Dioxo-thiazolidin-5-ylidenemethyl)-quinazolin-4-yl]-pyrrolidine-2-carboxylic acid,
5-(4-Methylamino-quinazolin-6-ylmethylene)-thiazolidine-2,4-dione,
5-(4-Methoxy-quinazolin-6-ylmethylene)-thiazolidine-2,4-dione
2-Imino-5-(4-methylamino-quinazolin-6-ylmethylene)-thiazolidin-4-one,
2-Imino-5-(4-piperidine-quinazolin-6-ylmethylene)-thiazolidin-4-one,
2-Imino-5-(4-dimethylamino-quinazolin-6-ylmethylene)-thiazolidin-4-one,
5-(2-Methyl-2H-benzotriazol-5-ylmethylene)-thiazolidine-2,4-dione,
5-(3-Methyl-3H-benzotriazol-5-ylmethylene)-thiazolidine-2,4-dione,
5-(3-Ethyl-3H-benzoimidazol-5-ylmethylene)-thiazolidine-2,4-dione,
5-{[1-(4-phenylbutyl)-1H-benzimidazol-6-yl]methylene}-1,3-thiazolidine-2,4-dione,
5-[(1-prop-2-yn-1-yl-H-benzimidazol-6-yl)methylene]-1,3-thiazolidine-2,4-dione,
5-[(1-{2-[4-(trifluoromethyl)phenyl]ethyl}-1H-benzimidazol-6-yl)methylene]-1,3-thiazolidine-2,4-dione,
5-([1-{2-(4-hydroxyphenyl)ethyl]-1H-benzimidazol-6-yl}methylene)-1,3-thiazolidine-2,4-dione,
methyl 4-{6-[(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]-1H-benzimidazol-1-yl}cyclohexanecarboxylate,
5-({1-[2-(5-methoxy-1H-indol-3-yl)ethyl]-1H-benzimidazol-6-yl}methylene)-1,3-thiazolidine-2,4-dione,
5-({1-[(1-methyl-1H-pyrazol-4-yl)methyl]-1H-benzimidazol-6-yl}methylene)-1,3-thiazolidine-2,4-dione,
5-({1-[2-(3,4-dimethoxyphenyl)ethyl]-1H-benzimidazol-6-yl}methylene)-1,3-thiazolidine-2,4-dione,
5-({1-[2-(4-phenoxyphenyl)ethyl]-1H-benzimidazol-6-yl}methylene)-1,3-thiazolidine-2,4-dione,
5-({1-[4-(trifluoromethyl)benzyl]-1H-benzimidazol-6-yl}methylene)-1,3-thiazolidine-2,4-dione,
4-{6-[(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]-1H-benzimidazol-1-yl}cyclohexanecarboxylic acid,
5-[(1-isobutyl-1H-benzimidazol-6-yl)methylene]-1,3-thiazolidine-2,4-dione,
5-({1-[2-(1,3-benzodioxol-4-yl)ethyl]-1H-benzimidazol-6-yl}methylene)-1,3-thiazolidine-2,4-dione,
5-({1-[2-(2-phenoxyphenyl)ethyl]-1H-benzimidazol-6-yl}methylene)-1,3-thiazolidine-2,4-dione,
5-{[1-(3,3-diphenylpropyl)-1H-benzimidazol-6-yl]methylene}-1,3-thiazolidine-2,4-dione,
5-{[1-(2-methoxybenzyl)-1H-benzimidazol-6-yl]methylene}-1,3-thiazolidine-2,4-dione,
5-{[1-(3-furylmethyl)-1H-benzimidazol-6-yl]methylene}-1,3-thiazolidine-2,4-dione,
5-[(1-propyl-1H-benzimidazol-6-yl)methylene]-1,3-thiazolidine-2,4-dione,
5-Quinoxalin-6-ylmethylene-thiazolidine-2,4-dione,
5-Quinoxalin-6-ylmethylene-2-thioxo-thiazolidin-4-one,
2-Imino-5-quinoxalin-6-ylmethylene-thiazolidin-4-one,
5-Benzothiazol-6-ylmethylene-thiazolidine-2,4-dione,
5-(3-Methyl-benzofuran-5-ylmethylene)-thiazolidine-2,4-dione,
5-(2-Bromo-3-methyl-benzofuran-5-ylmethylene)-thiazolidine-2,4-dione,
5-(3-bromo-benzofuran-5-ylmethylene)-thiazolidine-2,4-dione,
3-[5-(2,4-Dioxo-thiazolidin-5-ylidenemethyl)-benzofuran-3-yl]-acrylic acid ethyl ester,
3-[5-(2,4-Dioxo-thiazolidin-5-ylidenemethyl)-benzofuran-3-yl]-acrylic acid,
5-[3-(3-oxo-3-piperidin-1-yl-propenyl)-benzofuran-5-ylmethylene]-thiazolidine-2,4-dione,
Methyl 1-((3-{5-[(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]-1-benzofuran-3-yl}prop-2-enoyl)prolinate,
Methyl 1-((3-{5-[(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]-1-benzofuran-3-yl}prop-2-enoyl)-D-prolinate,
(5-({3-[(3-oxo-3-pyrrolidin-1-ylprop-1-en-1-yl]-1-benzofuran-5-yl}methylene)-1,3-thiazolidine-2,4-dione,
5-({3-[3-morpholin-4-yl-3-oxoprop-1-en-1-yl]-1-benzofuran-5-yl}methylene)-1,3-thiazolidine-2,4-dione,
Methyl 1-(3-{5-[(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]-1-benzofuran-3-yl}prop-2-enoyl)-L-prolinate,
N-cyclohexyl-3-{5-[(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]-1-benzofuran-3-yl)-N-methylacrylamide,
3-{5-[(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]-1-benzofuran-3-yl}-N-ethyl-N-(2-hydroxyethyl)acrylamide,
N-cyclobutyl-3-{5-[(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]-1-benzofuran-3-yl}acrylamide,
5-({3-[3-azetidin-1-yl-3-oxoprop-1-en-1-yl]-1-benzofuran-5-yl}methylene)-1,3-thiazolidine-2,4-dione,
5-({3-[3-(1,3-dihydro-2H-isoindol-2-yl)-3-oxoprop-1-en-1-yl]-1-benzofuran-5-yl}methylene)-1,3-thiazolidine-2,4-dione,
5-({3-[3-azepan-1-yl-3-oxoprop-1-en-1-yl]-1-benzofuran-5-yl}methylene)-1,3-thiazolidine-2,4-dione,
3-{5-[(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]-1-benzofuran-3-yl}-N-piperidin-1-ylacrylamide,
3-{5-[(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]-1-benzofuran-3-yl}-N-(pyridin-3-ylmethyl)acrylamide,
N-cyclohexyl-3-{5-[(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]-1-benzofuran-3-yl}acrylamide,
5-({3-[3-(4-methylpiperazin-1-yl)-3-oxoprop-1-en-1-yl]-1-benzofuran-5-yl}methylene)-1,3-thiazolidine-2,4-dione,
N-cycloheptyl-3-{5-[(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]-1-benzofuran-3-yl}acrylamide,
5-({3-[3-(2,5-dihydro-1H-pyrrol-1-yl)-3-oxoprop-1-en-1-yl]-1-benzofuran-5-yl}methylene)-1,3-thiazolidine-2,4-dione,
N-cyclopentyl-3-{5-[(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]-1-benzofuran-3-yl}acrylamide,
3-[5-(2,4-Dioxo-thiazolidin-5-ylidenemethyl)-benzofuran-3-yl]-propionic acid ethyl ester,
3-[5-(2,4-Dioxo-thiazolidin-5-ylidenemethyl)-benzofuran-3-yl]-propionic acid,
5-[3-(3-oxo-3-piperidin-1-yl-propyl)-benzofuran-5-ylmethylene]-thiazolidine-2,4-dione,
6-(2,4-Dioxo-thiazolidin-5-ylidenemethyl)-2,3-dihydro-benzo[1,4]oxazine-4-carboxylic acid tert-butyl ester,
5-(3,4-Dihydro-2H-benzo[1,4]oxazin-6-ylmethylene)-thiazolidine-2,4-dione,
5-(4-Benzoyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethylene)-thiazolidine-2,4-dione,
5-(4-Acetyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethylene)-thiazolidine-2,4-dione,
6-(2,4-Dioxo-thiazolidin-5-ylidenemethyl)-benzo[1,4]oxazine-4-carboxylic acid tert-butyl ester,
[6-(2,4-Dioxo-thiazolidin-5-ylidenemethyl)-3-oxo-2,3-dihydro-benzo[1,4]-oxazin-4-yl]-acetic acid methyl ester,
N-Benzyl-2-[6-(2,4-dioxo-thiazolidin-5-ylidenemethyl)-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl]-acetamide,
5-(4-Butyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethylene)-thiazolidine-2,4-dione,
5-(4-Benzyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethylene)-thiazolidine-2,4-dione,
5-(2-Chloro-benzofuran-5-ylmethylene)-thiazolidine-2,4-dione,
5-(3-Amino-benzo[d]isoxazol-5-ylmethylene)-thiazolidine-2,4-dione,
5-(3-Phenylethynyl-benzofuran-5-ylmethylene)-thiazolidine-2,4-dione,
5-Benzo[1,2,5]thiadiazol-5-ylmethylene-thiazolidine-2,4-dione,
5-Benzo[1,2,5]oxadiazol-5-ylmethylene-thiazolidine-2,4-dione,
5-(2-Methyl-benzofuran-6-ylmethylene)-thiazolidine-2,4-dione,
5-(2-Carboxymethyl-benzofuran-6-ylmethylene)-thiazolidine-2,4-dione,
5-(3-Bromo-2-fluoro-2,3-dihydro-benzofuran-6-ylmethylene)-thiazolidine-2,4-dione, and
5-(2-Fluoro-benzofuran-6-ylmethylene)-thiazolidine-2,4-dione.
20. A method of preparing a medicament, comprising, contacting the thiazolidinone-vinyl fused-benzene according to claim 13 , with one or more pharmaceutically acceptable additives.
21. A pharmaceutical composition, comprising at least one thiazolidinone-vinyl fused-benzene according to claim 13 , and a pharmaceutically acceptable carrier, diluent or excipient thereof.
22. A method for the treatment of inflammation, the method comprising administering to a subject in need thereof, an effective amount of the thiazolidinone-vinyl fused-benzene according to claim 13 .
23. A method of preparing a thiazolidinone-vinyl fused-benzene of formula (II), according to claim 14 , comprising the following step:
wherein R 1 , R 2 , Y 1 , Z and n are as above defined in formula (II).
24. A method of preparing a thiazolidinone-vinyl fused-benzene of formula (III), according to claim 17 , comprising the following step:
wherein R 1 , R 2 are as above defined for formula (III), and
Y 1 is 0, S or NH.
25. A composition, comprising, a pharmaceutically acceptable carrier, diluent or excipient and at least one compound according to formula (I):
as well as its geometrical isomers, its optically active forms as enantiomers, diastereomers and its racemate forms, as well as pharmaceutically acceptable salts thereof, wherein
A is a 5-8 membered heterocyclic group;
X is S or O;
Y 1 and Y 2 are independently S or O;
Z is S or O;
R 1 is H, CN, carboxy, acyl, C 1 -C 6 -alkoxy, halogen, hydroxy, acyloxy, C 1 -C 6 -alkyl carboxy, C 1 -C 6 -alkyl acyloxy, alkoxy, alkoxycarbonyl, C 1 -C 6 -alkyl alkoxycarbonyl, aminocarbonyl, C 1 -C 6 -alkyl aminocarbonyl, acylamino, C 1 -C 6 -alkyl acylamino, ureido, C 1 -C 6 -alkyl ureido, amino, C 1 -C 6 -alkyl amino, ammonium, sulfonyloxy, C 1 -C 6 -alkyl sulfonyloxy, sulfonyl, sulfonyl, sulfinyl, C 1 -C 6 -alkyl sulfinyl, sulfanyl, C 1 -C 6 -alkyl sulfanyl, sulfonylamino, C 1 -C 6 -alkyl sulfonylamino or carbamate;
R 2 is selected from the group consisting of H, halogen, acyl, amino, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -alkyl carboxy, C 1 -C o -alkyl acyl, C 1 -C o -alkyl alkoxycarbonyl, C 1 -C 6 -alkyl aminocarbonyl, C 1 -C 6 -alkyl acyloxy, C 1 -C 6 -alkyl acylamino, C 1 -C 6 -alkyl ureido, C 1 -C 6 -alkyl amino, C 1 -C 6 -alkyl alkoxy, C 1 -C 6 -alkyl sulfanyl, C 1 -C 6 -alkyl sulfinyl, C 1 -C 6 -alkyl sulfonyl, C 1 -C 6 -alkyl sulfonylaminoaryl, aryl, C 3 -C 8 -cycloalkyl or heterocycloalkyl, C 1 -C o -alkyl aryl, C 2 -C 6 -alkenyl-aryl, C 2 -C 6 -alkynyl aryl, carboxy, cyano, hydroxy, C 1 -C 6 -alkoxy, nitro, acylamino, ureido, C 1 -C 6 -alkyl carbamate, sulfonylamino, sulfanyl, or sulfonyl;
n is 0, 1 or 2;
with the proviso that the following compounds are excluded:
wherein R 1 is a lower alkyl or aralkyl and R 2 is H or a halogen.