Synthesis And Evaluation Of Newer Quinoline Derivatives Of Thiazolidinediones For Their Antidiabetic Activity

Abstract

In view of various biological activities of both thiazolidinediones and quinoline derivatives like antidiabetic, antifungal, antitumoral, anti-inflammatory, retinoidal, anti atherosclerotic activities, it was our interest to prepare various thiazolidinedione derivatives with a quinoline ring moiety and to evaluate them for antidiabetic activity. 5-(4-fluorobenzyl)-2,4-thiazolidinedione was synthesized by reaction of 4-fluoroaniline with methyl acrylate to give crude 2-Bromo-3-(4-fluoro-phenyl)-propionic acid methyl ester as an oil which was treated with thiourea in presence of sodium acetate and ethanol to give 5-(4-fluoro-benzyl)-2-imino-thiazolidine-4-one which on oxidation gave 5-(4-fluoro-benzyl)thiazolidine-2,4-dione. This was condensed with the quinoline derivatives in presence of Tetrahydrofuran. Among the synthesized derivatives five of them were screened for oral hypoglycemic activity, the compounds SK, SK-3 were showing significant activity and compound SK2 was showing moderate activity and compounds SK-4 and SK-5 were active. The structures of newly synthesized compounds were established on the basis of elemental analysis, TLC, IR and 1H NMR spectral studies.