title: Structure-activity relationships and molecular modeling of the N-(3-pivaloyloxy-2-benzylpropyl)-N'-[4-(methylsulfonylamino)benzyl] thiourea template for TRPV1 antagonism.
abstract: The structure-activity relationships of N-(3-acyloxy-2-benzylpropyl)-N'-4-[(methylsulfonylamino)benzyl] thioureas, which represent simplified RTX-based vanilloids, were investigated by varying the distances between the four principal pharmacophores and assessing binding and antagonistic activity on rTRPV1. The analysis indicated that a 3-pivaloyloxy-2-benzylpropyl C-region conferred the best potency in binding affinity and antagonism. The molecular modeling of this best template with the tetrameric homology model of rTRPV1 was performed to identify its binding interactions with the receptor.
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
authors.forename: Rahul S
authors.initials: RS
authors.lastname: Bhondwe
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Kang
authors.forename: Myeong Seop
authors.initials: MS
authors.lastname: Kim
authors.forename: Ho Shin
authors.initials: HS
authors.lastname: Kim
authors.forename: Seul-gi
authors.initials: SG
authors.lastname: Park
authors.forename: Karam
authors.initials: K
authors.lastname: Son
authors.forename: Sun
authors.initials: S
authors.lastname: Choi
authors.forename: Krystle A Lang
authors.initials: KA
authors.lastname: Kuhs
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Pavlyukovets
authors.forename: Larry V
authors.initials: LV
authors.lastname: Pearce
authors.forename: Peter M
authors.initials: PM
authors.lastname: Blumberg
authors.forename: Jeewoo
authors.initials: J
authors.lastname: Lee
mesh_terms: D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D056004:Molecular Dynamics Simulation; D017434:Protein Structure, Tertiary; D051381:Rats; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013890:Thiourea / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D013890:Thiourea