Novel 3-phenylprop-2-ynylamines as inhibitors of mammalian squalene epoxidase.
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.
Musso
David L
DL
GlaxoSmithKline Research and Development, Five Moore Dr., Research Triangle Park, NC 27709, USA. Dave.L.Musso@gsk.com
Clarke
Morris J
MJ
Kelley
James L
JL
Boswell
G Evan
GE
Chen
Grace
G
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
D000588:Amines; D001555:Benzene Derivatives; D004791:Enzyme Inhibitors; D010105:Oxygenases; D050603:Squalene Monooxygenase