title: Aminoquinazolines as TRPV1 antagonists: modulation of drug-like properties through the exploration of 2-position substitution.
abstract: A focused SAR exploration of the lead 4-aminoquinazoline TRPV1 antagonist 2 led to the discovery of compound 18. In rats, compound 18 is readily absorbed following oral dosing and demonstrates excellent in vivo potency and efficacy in an acute inflammatory pain model.
authors.affiliation: Neurogen Corporation, 35 N. E. Industrial Road, Branford, CT 06405, USA. cablum@comcast.net
authors.forename: Charles A
authors.initials: CA
authors.lastname: Blum
authors.forename: Xiaozhang
authors.initials: X
authors.lastname: Zheng
authors.forename: Harry
authors.initials: H
authors.lastname: Brielmann
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Hodgetts
authors.forename: Rajagopal
authors.initials: R
authors.lastname: Bakthavatchalam
authors.forename: Jayaraman
authors.initials: J
authors.lastname: Chandrasekhar
authors.forename: James E
authors.initials: JE
authors.lastname: Krause
authors.forename: Daniel
authors.initials: D
authors.lastname: Cortright
authors.forename: David
authors.initials: D
authors.lastname: Matson
authors.forename: Marci
authors.initials: M
authors.lastname: Crandall
authors.forename: Chu K
authors.initials: CK
authors.lastname: Ngo
authors.forename: Lawrence
authors.initials: L
authors.lastname: Fung
authors.forename: Marta
authors.initials: M
authors.lastname: Day
authors.forename: Mark
authors.initials: M
authors.lastname: Kershaw
authors.forename: Stéphane
authors.initials: S
authors.lastname: De Lombaert
authors.forename: Bertrand L
authors.initials: BL
authors.lastname: Chenard
mesh_terms: D000634:Aminoquinolines / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004285:Dogs; D015195:Drug Design; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000737:chemistry; D007249:Inflammation / Q000188:drug therapy; D007700:Kinetics; D008956:Models, Chemical; D008968:Molecular Conformation; D010146:Pain / Q000188:drug therapy; D004364:Pharmaceutical Preparations / Q000737:chemistry; D051381:Rats; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D000634:Aminoquinolines; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D004364:Pharmaceutical Preparations; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C494484:TRPV1 receptor