Alpha-substituted N-(4-tert-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea analogues as potent and stereospecific TRPV1 antagonists.
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).
Chung
Jae-Uk
JU
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
Kim
Su Yeon
SY
Lim
Ju-Ok
JO
Choi
Hyun-Kyung
HK
Kang
Sang-Uk
SU
Yoon
Hae-Seok
HS
Ryu
Hyungchul
H
Kang
Dong Wook
DW
Lee
Jeewoo
J
Kang
Bomi
B
Choi
Sun
S
Toth
Attila
A
Pearce
Larry V
LV
Pavlyukovets
Vladimir A
VA
Lundberg
Daniel J
DJ
Blumberg
Peter M
PM
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*
D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D013890:Thiourea; D002211:Capsaicin; D002118:Calcium