Design and synthesis of benzoxazole containing indole analogs as peroxisome proliferator-activated receptor-γ/δ dual agonists

A series of benzoxazole or benzothiazole containing indole analogs, 6-alkoxyindole-2-carboxylic acids and 5-alkoxy-3-indolylacetic acids, were synthesized as novel candidates of PPAR gamma/delta dual agonists and their ligand activities for PPAR subtypes (alpha, gamma and delta) were investigated. In transient transactivation assay, several compounds activated PPAR gamma and delta with little activity of PPAR alpha. Putative binding mode of the compounds 1a and 2a in the active site of PPAR gamma was similar with that of rosiglitazone and the molecular modeling provides molecular insight to the observed activity. (C) 2011 Elsevier Ltd. All rights reserved.