Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV1

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

Authors: 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

Journal, date & volume: Bioorg. Med. Chem., 2012 Jan 1 , 20, 215-24

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22169633

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.