Design and Synthesis of Benzimidazole-Linked meta-Substituted Benzylidenes/Benzyls as Biologically Significant New Chemical Entities

Abstract

meta-Linked thiazolidinedione (TZD)– and diethyl malonate (DEM)–based benzylidenes and methyl acetoacetate (MAA)–based benzyl moieties linked to the 2-position of N-methyl benzimidazole were synthesized. TZD- and DEM-based compounds were synthesized by condensation of 2,4-thiazolidinedone and DEM respectively with the corresponding 3-substituted benzaldehyde, whereas MAA-based compounds were obtained by halogen displacement with the corresponding 3-substituted phenol. These new chemical entities were designed to provide a balanced agonism at the peroxisome proliferator activated receptor alpha/gamma (PPARα/γ) in the management of type 2 diabetes: a move from glitazones to selective PPARγ modulators (SPPARγMs). Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.