title: N-4-t-Butylbenzyl 2-(4-methylsulfonylaminophenyl) propanamide TRPV1 antagonists: Structure-activity relationships in the A-region.
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.
authors.affiliation: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Yong Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Kil
authors.forename: Sang-Uk
authors.initials: SU
authors.lastname: Kang
authors.forename: HyungChul
authors.initials: H
authors.lastname: Ryu
authors.forename: Myeong Seop
authors.initials: MS
authors.lastname: Kim
authors.forename: Yongsung
authors.initials: Y
authors.lastname: Cho
authors.forename: Rahul S
authors.initials: RS
authors.lastname: Bhondwe
authors.forename: Shivaji A
authors.initials: SA
authors.lastname: Thorat
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.forename: Keliang
authors.initials: K
authors.lastname: Liu
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Sun
authors.initials: S
authors.lastname: Choi
authors.forename: Larry V
authors.initials: LV
authors.lastname: Pearce
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Pavlyukovets
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Morgan
authors.forename: Richard
authors.initials: R
authors.lastname: Tran
authors.forename: Jozsef
authors.initials: J
authors.lastname: Lazar
authors.forename: Peter M
authors.initials: PM
authors.lastname: Blumberg
authors.forename: Jeewoo
authors.initials: J
authors.lastname: Lee
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D003198:Computer Simulation; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D006860:Hydrogen Bonding; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000577:Amides; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human