Synthesis and evaluation of thiazole carboxamides as vanilloid receptor 1 (TRPV1) antagonists.
A thiazole derivative, 2-(2,6-dichlorobenzyl)-N-(4-isopropylphenyl) thiazole-4-carboxamide (1), was identified as a TRPV1 antagonist. We synthesized various thiazole analogs and evaluated them for their ability to block capsaicin- or acid-induced calcium influx in TRPV1-expressing CHO cells. The IC(50) values of the most potent antagonists were ca. 0.050microM in these assays.
Xi
Ning
N
Chemistry Research and Discovery, Amgen Inc., One Amgen Center Dr., Thousand Oaks, CA 91320, USA. nxi@amgen.com
Bo
Yunxin
Y
Doherty
Elizabeth M
EM
Fotsch
Christopher
C
Gavva
Narender R
NR
Han
Nianhe
N
Hungate
Randall W
RW
Klionsky
Lana
L
Liu
Qingyian
Q
Tamir
Rami
R
Xu
Shimin
S
Treanor
James J S
JJ
Norman
Mark H
MH
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D015394:Molecular Structure; D010072:Oxamic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D000577:Amides; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D013844:Thiazoles; D010072:Oxamic Acid