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

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12 Scopus citations

Abstract

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
Volume20
Issue number1
DOIs
StatePublished - 1 Jan 2012

Keywords

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

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