The SAR analysis of TRPV1 agonists with the α-methylated B-region

  • Bioorg Med Chem Lett. 2012 Aug 15;22(16):5227-31. doi: 10.1016/j.bmcl.2012.06.059.
Yongsung Cho  1 ,  Myeong Seop Kim ,  Ho Shin Kim ,  Jihyae Ann ,  Jiyoun Lee ,  Larry V Pearce ,  Vladimir A Pavlyukovets ,  Matthew A Morgan ,  Peter M Blumberg ,  Jeewoo Lee
Affiliations
  • 1. Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
PMID: 22796184 DOI: 10.1016/j.bmcl.2012.06.059
Abstract

A series of TRPV1 agonists with amide, reverse amide, and thiourea groups in the B-region and their corresponding α-methylated analogues were investigated. Whereas the α-methylation of the amide B-region enhanced the binding affinities and potencies as agonists, that of the reverse amide and thiourea led to a reduction in receptor affinity. The analysis indicated that proper hydrogen bonding as well as steric effects in the B-region are critical for receptor binding.