α-Methylated simplified resiniferatoxin (sRTX) thiourea analogues as potent and stereospecific TRPV1 antagonists

Bioorg Med Chem Lett. 2014 Jun 15;24(12):2685-8. doi: 10.1016/j.bmcl.2014.04.054. Epub 2014 Apr 23.

Abstract

A series of α-methylated analogues of the potent sRTX thiourea antagonists were investigated as rTRPV1 ligands in order to examine the effect of α-methylation on receptor activity. The SAR analysis indicated that activity was stereospecific with the (R)-configuration of the newly formed chiral center providing high binding affinity and potent antagonism while the configuration of the C-region was not significant.

Keywords: Capsaicin; Resiniferatoxin; TRPV1 antagonist; Vanilloid receptor 1.

Publication types

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

MeSH terms

  • Animals
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Diterpenes / chemical synthesis*
  • Diterpenes / chemistry
  • Diterpenes / pharmacology*
  • Humans
  • Methylation
  • Molecular Structure
  • Protein Binding / drug effects
  • Rats
  • Stereoisomerism
  • Structure-Activity Relationship
  • TRPV Cation Channels / antagonists & inhibitors*
  • Thiourea / analogs & derivatives
  • Thiourea / chemical synthesis*
  • Thiourea / chemistry
  • Thiourea / pharmacology*

Substances

  • Diterpenes
  • TRPV Cation Channels
  • resiniferatoxin
  • Thiourea