Structure-activity relationships and molecular modeling of the N-(3-pivaloyloxy-2-benzylpropyl)-N′-[4-(methylsulfonylamino)benzyl] thiourea template for TRPV1 antagonism

Rahul S. Bhondwe, Dong Wook Kang, Myeong Seop Kim, Ho Shin Kim, Seul Gi Park, Karam Son, Sun Choi, Krystle A. Lang Kuhs, Vladimir A. Pavlyukovets, Larry V. Pearce, Peter M. Blumberg, Jeewoo Lee

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The structure-activity relationships of N-(3-acyloxy-2-benzylpropyl)- N′-4-[(methylsulfonylamino)benzyl] thioureas, which represent simplified RTX-based vanilloids, were investigated by varying the distances between the four principal pharmacophores and assessing binding and antagonistic activity on rTRPV1. The analysis indicated that a 3-pivaloyloxy-2-benzylpropyl C-region conferred the best potency in binding affinity and antagonism. The molecular modeling of this best template with the tetrameric homology model of rTRPV1 was performed to identify its binding interactions with the receptor.

Original languageEnglish
Pages (from-to)3656-3660
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number11
DOIs
StatePublished - 1 Jun 2012

Keywords

  • Capsaicin
  • Molecular modeling
  • Resiniferatoxin
  • TRPV1 antagonist
  • Vanilloid receptor 1

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