title: Conformationally constrained analogues of N'-(4-tert-butylbenzyl)-N-(4-methylsulfonylaminobenzyl)thiourea as TRPV1 antagonists.
abstract: A series of bicyclic analogues having indan and tetrahydronaphthalene templates in the A-region were designed as conformationally constrained analogues of our previously reported potent TRPV1 antagonists (1, 3). The activities for rat TRPV1 of the conformationally restricted analogues were moderately or markedly diminished, particularly in the case of the tetrahydronaphthalene analogues. The analysis indicated that steric constraints at the benzylic position in the bicyclic analogues may be an important factor for their unfavorable interaction with the receptor.
authors.affiliation: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim-Dong, Kwanak-Ku, Seoul 151-742, Republic of Korea.
authors.forename: Ju-Ok
authors.initials: JO
authors.lastname: Lim
authors.forename: Mi-Kyoung
authors.initials: MK
authors.lastname: Jin
authors.forename: HyungChul
authors.initials: H
authors.lastname: Ryu
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Kang
authors.forename: Jeewoo
authors.initials: J
authors.lastname: Lee
authors.forename: Larry V
authors.initials: LV
authors.lastname: Pearce
authors.forename: Richard
authors.initials: R
authors.lastname: Tran
authors.forename: Attila
authors.initials: A
authors.lastname: Toth
authors.forename: Peter M
authors.initials: PM
authors.lastname: Blumberg
mesh_terms: D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007189:Indans; D008968:Molecular Conformation; D009281:Naphthalenes; D051381:Rats; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D007189:Indans; D009281:Naphthalenes; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C031721:naphthalene; D013890:Thiourea; C093582:indan