Halogenation of 4-hydroxy-3-methoxybenzyl thiourea TRPV1 agonists showed enhanced antagonism to capsaicin

Dong Wook Kang, Hyung Chul Ryu, Jeewoo Lee, Krystle A. Lang, Vladimir A. Pavlyukovets, Larry V. Pearce, Tetsurou Ikeda, Jozsef Lazar, Peter M. Blumberg

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Selected potent TRPV1 agonists (1-6) have been modified by 5- or 6-halogenation on the aromatic A-region to analyze their effects on potency and efficacy (agonism versus antagonism). The halogenation caused enhanced functional antagonism at TRPV1 compared to the corresponding prototype agonists. The analysis of SAR indicated that the antagonism was enhanced as the size of the halogen increased (I > Br > Cl) and when the 6-position was halogenated. Compounds 23c and 31b were found to be potent full antagonists with Ki (as functional antagonist) = 23.1 and 30.3 nM in rTRPV1/CHO system, respectively.

Original languageEnglish
Pages (from-to)214-219
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Issue number1
StatePublished - Jan 1 2007

Bibliographical note

Funding Information:
This work was supported by Grant R01-2004-000-10132-0 from the Basic Research Program of the Korea Science and Engineering Foundation and this research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. We thank Matthew A. Morgan, Andrew K. Tao, and Christopher B. Ryder for technical assistance.


  • Capsaicinoid
  • Halogenation
  • Resiniferatoxin
  • TRPV1 agonist
  • TRPV1 antagonist

ASJC Scopus subject areas

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


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