Patent EA-004301-B1 (EA)
Title: Novel thiazolidinedione derivatives as antidiabetic agents
Inventor: MOURELLE MANCINI MARISABEL
IPC: A61P5/00
Filed: 2000-11-15
Abstract: 1. A compound of the general formula (I): wherein: R1 is H or C1-C6 alkyl, R2 - H, C1-C6 alkyl, halogen (F, Cl, Br, I), -OR5, -SR5, -NR5R6, -NO2, or phenyl; R3 - H, C1-C6 alkyl, halogen (F, Cl, Br, I), -OR5, -SR5, -NR5R6, -NO2, or phenyl; R4 - H, C1-C6 alkyl, halogen (F, Cl, Br, I), -OR5, NR5R6, or phenyl; R3 and R4, are taken together, are -CH = CH-CH = CH-, -N=CR7-NR8- or -NR8-CR7=N-, forming a fused ring on the pyrimidine ring. R5, R6: independently to each other, may be H or C1-C6 alkyl, R7 - H or NH2, R8 - H, C1-C6 alkyl, as well as the pharmaceutically acceptable salts and tautomeric forms thereof. 2. A compound of the general formula (I) according to Claim 1, wherein: R1 is methyl; R2 - H, -OR5, -NR5R6; R3 - H, halogen (F, Cl, Br, I), -OR5- group; R4 - H or R3, R4, are taken together, are -NR8-CR7=N- or -N=CR7-NR8-group; wherein R7 and R8 are as previously defined. 3. A compound of the general formula (I) according to Claim 1, characterized in that it is selected from one of the following: 5-{4-[2-(Methylpyrimidin-4-yl-amino]-ethoxy)-benzyl}-thiazolidine-2,4-dione 5-{4-{2-[(6-Chloropyrimidin-4-yl)-methylamino]-ethoxy}-benzyl)-thiazolidine-2,9-dione 5-(4-{2-[(2-Amino-6-chloropyrimidin-4-yl)-methylamino]-ethoxy}-benzyl)-thiazolidine-2,4-dione 5-(4-{2-[(2,6-Dimethoxypyrimidin-4-yl)-methylamino]-ethoxy}-benzyl)-thiazolidine-2,4-dione 5-(4-{2-[Methyl-(7H-purin-6-yl)-amino]-ethoxy}-benzyl)-thiazolidine-2,4-dione 5-(4-{2-[Methyl-(9-methyl-9H-purin-6-yl)amino]ethoxy}-benzyl)thiazolidine-2,4-dione 5-(4-{2-[(6-Methoxypyrimidin-4-yl)-methylamino]-ethoxy}-benzyl)-thiazolidine-2,4-dione 5-(4-{2-[(6-Hydroxypyrimidin-4-yl)-methylamino]-ethoxy}-benzyl)-thiazolidine-2,4-dione. 4. A process for the preparation of a compound according to Claim 1, characterized in that a compound of the general formula (III) is reacted with a compound of the formula (II): wherein R1, R2, R3 and R4 are as previously defined; and X is a leaving group such as a halogen, especially Cl or Br, in a inert medium at a temperature ranging from 10 to 120 degree C. 5. A process for the preparation of a compound according to Claim 1, which comprises the reduction of a compound of the formula (VI): wherein R1, R2, R3 and R4, are as previously defined. 6. A process according to Claim 5, characterized in that said reduction reaction is carried out with sodium borohydride, with metals in the presence or not of a proton-donor, by enzymatic reduction or by catalytic. hydrogenation. 7. A pharmaceutical composition which comprises a compound of the general formula (I) according to anyone of Claims 1 to 3, and a pharmaceutically acceptable carrier, for the treatment and/or prevention of hyperglycemia and/or hyperlipidemia and/or for the treatment of complications associated to the resistance to the insulin, such as hypertension, hyperuricemia or other cardiovascular, metabolic and endocrine conditions. 8. The use of a compound of the general formula (I) according to anyone of Claims 1 to 3, alone or in combination with one or more other antidiabetic agents such as sulfonylureas or biguanides, for the production of a medicament for the treatment and/or prevention of hyperglycemia and/or hyperlipidemia, and/or for the treatment of complications associated to the resistance to the insulin, such as hypertension, hyperuricemia or other cardiovascular, metabolic and endocrine conditions.