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. Epub 2012 Jun 23.

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry
  • Amides / metabolism
  • Methylation
  • Protein Binding
  • Stereoisomerism
  • Structure-Activity Relationship
  • TRPV Cation Channels / agonists*
  • TRPV Cation Channels / metabolism
  • Thiourea / chemical synthesis
  • Thiourea / chemistry
  • Thiourea / metabolism

Substances

  • Amides
  • TRPV Cation Channels
  • Thiourea