title: N-Tetrahydroquinolinyl, N-quinolinyl and N-isoquinolinyl biaryl carboxamides as antagonists of TRPV1.
abstract: Starting from the high throughput screening hit (3), novel N-tetrahydroquinolinyl, N-quinolinyl and N-isoquinolinyl carboxamides have been identified as potent antagonists of the ion channel TRPV1. The N-quinolinylnicotinamide (46) showed excellent potency at human, guinea pig and rat TRPV1, a favourable in vitro DMPK profile and activity in an in vivo model of inflammatory pain.
authors.affiliation: Neurology and GI Center of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex, UK. sue.m.westaway@gsk.com
authors.forename: Susan M
authors.initials: SM
authors.lastname: Westaway
authors.forename: Ying-Kit
authors.initials: YK
authors.lastname: Chung
authors.forename: John B
authors.initials: JB
authors.lastname: Davis
authors.forename: Vicky
authors.initials: V
authors.lastname: Holland
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Jerman
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Medhurst
authors.forename: Harshad K
authors.initials: HK
authors.lastname: Rami
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Stemp
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Stevens
authors.forename: Mervyn
authors.initials: M
authors.lastname: Thompson
authors.forename: Kim Y
authors.initials: KY
authors.lastname: Winborn
authors.forename: James
authors.initials: J
authors.lastname: Wright
mesh_terms: D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D001549:Benzamides; D007546:Isoquinolines; D011804:Quinolines; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D002211:Capsaicin