title: Alpha-substituted N-(4-tert-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea analogues as potent and stereospecific TRPV1 antagonists.
abstract: A series of alpha-substituted N-(4-tert-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea analogues have been investigated as TRPV1 receptor antagonists. alpha-Methyl substituted analogues showed potent and stereospecific antagonism to the action of capsaicin on rat TRPV1 heterologously expressed in Chinese hamster ovary cells. In particular, compounds 14 and 18, which possess the R-configuration, exhibited excellent potencies (respectively, K(i)=41 and 39.2 nM and K(i(ant))=4.5 and 37 nM).
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Jae-Uk
authors.initials: JU
authors.lastname: Chung
authors.forename: Su Yeon
authors.initials: SY
authors.lastname: Kim
authors.forename: Ju-Ok
authors.initials: JO
authors.lastname: Lim
authors.forename: Hyun-Kyung
authors.initials: HK
authors.lastname: Choi
authors.forename: Sang-Uk
authors.initials: SU
authors.lastname: Kang
authors.forename: Hae-Seok
authors.initials: HS
authors.lastname: Yoon
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: Bomi
authors.initials: B
authors.lastname: Kang
authors.forename: Sun
authors.initials: S
authors.lastname: Choi
authors.forename: Attila
authors.initials: A
authors.lastname: Toth
authors.forename: Larry V
authors.initials: LV
authors.lastname: Pearce
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Pavlyukovets
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lundberg
authors.forename: Peter M
authors.initials: PM
authors.lastname: Blumberg
mesh_terms: D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D008958:Models, Molecular; D015394:Molecular Structure; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*; D013890:Thiourea / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D013890:Thiourea; D002211:Capsaicin; D002118:Calcium