title: Tetrahydroquinoline derivatives as opioid receptor antagonists.
abstract: Opioid receptors play an important role in both behavioral and homeostatic functions. We herein report tetrahydroquinoline derivatives as opioid receptor antagonists. SAR studies led to the identification of the potent antagonist 2v, endowed with 1.58nM (K(i)) functional activity against the μ opioid receptor. DMPK data suggest that novel tetrahydroquinoline analogs may be advantageous in peripheral applications.
authors.affiliation: Department of Medicinal Chemistry, GlaxoSmithKline, Research Triangle Park, NC 27709, USA. cunyu.a.zhang@gsk.com
authors.forename: Cunyu
authors.initials: C
authors.lastname: Zhang
authors.forename: Susan M
authors.initials: SM
authors.lastname: Westaway
authors.forename: Jason D
authors.initials: JD
authors.lastname: Speake
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bishop
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Goetz
authors.forename: Luz Helena
authors.initials: LH
authors.lastname: Carballo
authors.forename: Mike
authors.initials: M
authors.lastname: Hu
authors.forename: Andrea H
authors.initials: AH
authors.lastname: Epperly
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D009292:Narcotic Antagonists; D011804:Quinolines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D011957:Receptors, Opioid / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D009292:Narcotic Antagonists; D011804:Quinolines; D011957:Receptors, Opioid; C542964:1,2,3,4-tetrahydroquinoline