Structure-activity relationship (SAR) investigations of substituted imidazole analogs as TRPV1 antagonists.
A novel series of 4,5-biarylimidazoles as TRPV1 antagonists were designed based on the previously reported 4,6-disubstituted benzimidazole series. The analogs were evaluated for their ability to block capsaicin- or acid-induced calcium influx in TRPV1-expressing CHO cells. These studies led to the identification of a highly potent and orally bioavailable TRPV1 antagonist, imidazole 33.
Gore
Vijay K
VK
Chemistry Research & Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA. vgore@amgen.com
Ma
Vu V
VV
Tamir
Rami
R
Gavva
Narender R
NR
Treanor
James J S
JJ
Norman
Mark H
MH
D000284:Administration, Oral; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D007093:Imidazoles / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*
D007093:Imidazoles; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human