Synthesis and biological evaluation of isoxazole, oxazole, and oxadiazole containing heteroaryl analogs of biaryl ureas as DGAT1 inhibitors

► Identification of a 3-phenylisoxazole scaffold as potent inhibitor of hDGAT1. ► DGAT1 activity of 3-phenylisoxazoles translates to in vivo triglyceride reduction. ► 3-Phenylisoxazole analogs with improved cLogP result in improved solubility. ► Compound 40a may serve as a new lead for developing newer anti-obesity agents.