Discovery of Potent of New 4-oxothiazolidin-2-ylidene Derivatives Containing Piperidinyl Moiety against Aldose Reductase”

Abstract

2-(2-Oxo-2-(piperidin-1-yl)ethylidene)thiazolidin-4-one (1) was used as a key intermediate for the synthesis of many thiazolo[3,2-a] pyridine derivatives. Thus, 4-thiazolidinine (1) was refluxed with aromatic aldehydes where the corresponding 4-thiazolidinone derivatives (2a,b) were afforded. Cyclization of (2a,b) with malononitrile and aldehydes gave the corresponding thiazolo[3,2-a] pyridines (5a,b). Thiazolo[3,2-a] naphthyridine derivatives (6a,b) were obtained from the reaction of compounds (5a,b) with formic acid. Acylation of (5a,b) with acetic anhydride or benzoyl chloride for 2 h produced the corresponding amide derivatives (7,8). While, upon treatment of (5b) with acetic anhydride for 5 h furnished tricyclic structure (9). Furthermore, compounds (5a,b) were refluxed with either chloroacetonitrile to give thiazolo[3,2-a] pyrrolo [2,3-c] pyridines (10a,b) or with malononitrile to afford the corresponding thiazolo[3,2-a] naphthyridine derivatives (14a,b). In addition, the corresponding thiourea and Pyrazolo [3,4:4’,5] thiazolo derivatives (15) and (16) were produced via the reaction of 5 ethyl with ethylisothiocyanate and phenyl hydrazine. Molecular docking simulations into the active site of ALR2 were performed, and showed that, some of the synthesized compounds more suitable inhibitor against ALR2 with farther modification in future.