title: Structure-activity relationship (SAR) investigations of substituted imidazole analogs as TRPV1 antagonists.
abstract: 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.
authors.affiliation: Chemistry Research & Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA. vgore@amgen.com
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Gore
authors.forename: Vu V
authors.initials: VV
authors.lastname: Ma
authors.forename: Rami
authors.initials: R
authors.lastname: Tamir
authors.forename: Narender R
authors.initials: NR
authors.lastname: Gavva
authors.forename: James J S
authors.initials: JJ
authors.lastname: Treanor
authors.forename: Mark H
authors.initials: MH
authors.lastname: Norman
mesh_terms: 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*
chemical_list: D007093:Imidazoles; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human