Conformationally constrained analogues of N'-(4-tert-butylbenzyl)-N-(4-methylsulfonylaminobenzyl)thiourea as TRPV1 antagonists.
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.
Lim
Ju-Ok
JO
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.
Jin
Mi-Kyoung
MK
Ryu
HyungChul
H
Kang
Dong Wook
DW
Lee
Jeewoo
J
Pearce
Larry V
LV
Tran
Richard
R
Toth
Attila
A
Blumberg
Peter M
PM
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
D019086:Bridged Bicyclo Compounds, Heterocyclic; D007189:Indans; D009281:Naphthalenes; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C031721:naphthalene; D013890:Thiourea; C093582:indan