title: Novel 3-phenylprop-2-ynylamines as inhibitors of mammalian squalene epoxidase.
abstract: The synthesis of a novel series of 3-phenylprop-2-ynylamines as selective mammalian squalene epoxidase inhibitors is described. Structure activity relationship studies led to the discovery of compound 19, 1-[3-(3,5-dichlorophenyl)-prop-2-ynyl]-3- methylpiperidine hydrochloride with an IC50 of 2.8 +/- 0.6 microM against rat liver squalene epoxidase. Against 23 strains of fungal squalene epoxidase compound 19 was found to be inactive.
authors.affiliation: GlaxoSmithKline Research and Development, Five Moore Dr., Research Triangle Park, NC 27709, USA. Dave.L.Musso@gsk.com
authors.forename: David L
authors.initials: DL
authors.lastname: Musso
authors.forename: Morris J
authors.initials: MJ
authors.lastname: Clarke
authors.forename: James L
authors.initials: JL
authors.lastname: Kelley
authors.forename: G Evan
authors.initials: GE
authors.lastname: Boswell
authors.forename: Grace
authors.initials: G
authors.lastname: Chen
mesh_terms: D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D001555:Benzene Derivatives / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D005260:Female; D020128:Inhibitory Concentration 50; D010105:Oxygenases / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050603:Squalene Monooxygenase; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D001555:Benzene Derivatives; D004791:Enzyme Inhibitors; D010105:Oxygenases; D050603:Squalene Monooxygenase