Discovery of Novel TRPV1 Ligands through Rational Approach Based on Its Putative Endogenous Ligand, 12(S)-HPETE

摘要

We report design and synthesis of the novel TRPV1 ligands through a rational approach. Simplified analogues of 12(S)-HPETE showing TRPV1 agonistic effect are disclosed. Biological evaluation revealed that substitution of functional groups without any change in conformation converted agonist into antagonist. Our work provided key information with regard to TRPV1 agonist/antagonist switching.