Design, synthesis and computational validation of novel benzimidazole/indole-based PPARα and PPARγ partial agonists

Abstract

The design and synthesis of benzimidazolyl and indolyl linked α-alkoxy phenylpropanoic acid derivatives and the β-keto ester analogues in an effort to develop novel peroxisome proliferator activated receptors ligands expected to exhibit PPARα and PPARγ partial agonism in the management of hyperglycemia and hyperlipidemia for the treatment of type 2 diabetes is reported. Computational validation of the designed molecules through activity prediction and docking studies showed expected results. Syntheses of benzimidazole and indole linked benzyl based α-alkoxy propanoic acids and benzylidene and benzyl based β-ketoesters, as partial PPARα/γ agonists as Anti Type 2 Diabetic compounds, followed by their activity and binding affinity prediction at individual PPARs to support the design of the molecules with expected partial agonism, are reported.