Synthesis of benzamide derivatives as TRPV1 antagonists.

Abstract From hit compounds identified by high throughput screening (HTS), we have found compound 1 as a lead TRPV1 antagonist and confirmed its potential as a treatment for pain. Compound 1 has led to potent TRPV1 antagonistic benzamide derivatives ((±)- 2 : human IC 50  = 23 nM, (±)- 3 : human IC 50  = 14 nM in the capsaicin-induced calcium influx assay) containing indole and naphthyl moieties, obtained by elaboration of the tryptamine scaffold or via bioisosteric replacements.