title: Synthesis and evaluation of thiazole carboxamides as vanilloid receptor 1 (TRPV1) antagonists.
abstract: 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.
authors.affiliation: Chemistry Research and Discovery, Amgen Inc., One Amgen Center Dr., Thousand Oaks, CA 91320, USA. nxi@amgen.com
authors.forename: Ning
authors.initials: N
authors.lastname: Xi
authors.forename: Yunxin
authors.initials: Y
authors.lastname: Bo
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Doherty
authors.forename: Christopher
authors.initials: C
authors.lastname: Fotsch
authors.forename: Narender R
authors.initials: NR
authors.lastname: Gavva
authors.forename: Nianhe
authors.initials: N
authors.lastname: Han
authors.forename: Randall W
authors.initials: RW
authors.lastname: Hungate
authors.forename: Lana
authors.initials: L
authors.lastname: Klionsky
authors.forename: Qingyian
authors.initials: Q
authors.lastname: Liu
authors.forename: Rami
authors.initials: R
authors.lastname: Tamir
authors.forename: Shimin
authors.initials: S
authors.lastname: Xu
authors.forename: James J S
authors.initials: JJ
authors.lastname: Treanor
authors.forename: Mark H
authors.initials: MH
authors.lastname: Norman
mesh_terms: 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*
chemical_list: D000577:Amides; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D013844:Thiazoles; D010072:Oxamic Acid