Heterocycle-linked phenylbenzyl amides as novel TRPV1 antagonists and their TRPV1 binding modes: constraint-induced enhancement of in vitro and in vivo activities

Chem Asian J. 2013 Feb;8(2):400-9. doi: 10.1002/asia.201200730. Epub 2012 Dec 3.

Abstract

A series of heterocycle-linked constrained phenylbenzyl amides were found to be TRPV1 antagonists with promising in vivo profiles. In particular, one of the analogues containing a furan linker exhibited excellent TRPV1 antagonistic activity and in vivo analgesic efficacy. In addition, the binding modes of dibenzyl thiourea, benzylphenethyl amide, and furan-linked phenylbenzyl amide were examined by using the flexible docking study within the rTRPV1 homology model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry*
  • Amides / pharmacokinetics
  • Amides / therapeutic use
  • Analgesics / chemical synthesis
  • Analgesics / pharmacokinetics
  • Analgesics / therapeutic use
  • Animals
  • Binding Sites
  • Furans / chemistry
  • Half-Life
  • Heterocyclic Compounds / chemistry*
  • Hyperalgesia / chemically induced
  • Hyperalgesia / drug therapy
  • Male
  • Molecular Docking Simulation
  • Protein Structure, Tertiary
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics
  • TRPV Cation Channels / antagonists & inhibitors*
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism
  • Thiourea / chemistry

Substances

  • Amides
  • Analgesics
  • Furans
  • Heterocyclic Compounds
  • Recombinant Proteins
  • TRPV Cation Channels
  • Thiourea
  • furan