N-4-t-Butylbenzyl 2-(4-methylsulfonylaminophenyl) propanamide TRPV1 antagonists: Structure-activity relationships in the A-region

Yong Soo Kim, Min Jung Kil, Sang Uk Kang, Hyungchul Ryu, Myeong Seop Kim, Yongsung Cho, Rahul S. Bhondwe, Shivaji A. Thorat, Wei Sun, Keliang Liu, Jin Hee Lee, Sun Choi, Larry V. Pearce, Vladimir A. Pavlyukovets, Matthew A. Morgan, Richard Tran, Jozsef Lazar, Peter M. Blumberg, Jeewoo Lee

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Structure-activity relationships for the A-region in a series of N-4-t-butylbenzyl 2-(4-methylsulfonylaminophenyl) propanamides as TRPV1 antagonists have been investigated. Among them, the 3-fluoro analogue 54 showed high binding affinity and potent antagonism for both rTRPV1 and hTRPV1 in CHO cells. Its stereospecific activity was demonstrated with marked selectivity for the (S)-configuration (54S versus 54R). A docking study of 54S with our hTRPV1 homology model highlighted crucial hydrogen bonds between the ligand and the receptor contributing to its potency.

Original languageEnglish
Pages (from-to)215-224
Number of pages10
JournalBioorganic and Medicinal Chemistry
Issue number1
StatePublished - 1 Jan 2012

Bibliographical note

Funding Information:
This research was supported by Research Funding from Digitalbiotech, Grants R11–2007–107–02001-0 from the National Research Foundation of Korea (NRF), the National Core Research Center (NCRC) program (No. 2011-0006244) of MEST and NRF through the Center for Cell Signaling & Drug Discovery Research at Ewha Womans University, and the intramural program of the National Institutes of Health, Center for Cancer Research, National Cancer Institute (project Z1A BC 005270).


  • Analgesic
  • Capsaicin
  • Molecular modeling
  • Resiniferatoxin
  • TRPV1 antagonists


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