Asymmetric synthesis and receptor activity of chiral simplified resiniferatoxin (sRTX) analogues as transient receptor potential vanilloid 1 (TRPV1) ligands

Bioorg Med Chem Lett. 2014 Jan 1;24(1):382-5. doi: 10.1016/j.bmcl.2013.10.064. Epub 2013 Nov 6.

Abstract

The chiral isomers of the two potent simplified RTX-based vanilloids, compounds 2 and 3, were synthesized employing highly enantioselective PTC alkylation and evaluated as hTRPV1 ligands. The analysis indicated that the R-isomer was the eutomer in binding affinity and functional activity. The agonism of compound 2R was comparable to that of RTX. Docking analysis of the chiral isomers of 3 suggested the basis for its stereospecific activity and the binding mode of 3R.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diterpenes / chemical synthesis
  • Diterpenes / chemistry
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Ligands
  • Models, Molecular
  • Molecular Structure
  • Stereoisomerism
  • Structure-Activity Relationship
  • TRPV Cation Channels / agonists*
  • TRPV Cation Channels / antagonists & inhibitors*

Substances

  • Diterpenes
  • Ligands
  • TRPV Cation Channels
  • TRPV1 protein, human
  • resiniferatoxin