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 - Jun 1 2012

Bibliographical note

Funding Information:
This research was supported by Grants from the National Research Foundation of Korea (NRF) ( R11-2007-107-02001-0 ), Grants from the NLRL program (2011-0028885), Brain Research Center of the 21st Century Frontier Research Program (2011-K000289) funded by MEST and NRF, the Ewha Global Top 5 Grant 2011 of Ewha Womans University, and was supported in part by the Intramural Research Program of the National Institutes of Health, Center for Cancer Research, National Cancer Institute (Project Z1A BC 005270).

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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