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Amines Amines Q 0120Novel 3-Phenylprop-2-ynylamines as Inhibitors of Mammalian Squalene Epoxidase. -A number of novel 3-phenylprop-2-ynylamines (isolated as the hydrochloride salts) are prepared from phenylacetylenes and amines under Mannich conditions. Product (IVe) represents a new class of potent and selective inhibitors of mammalian squalene epoxidase which lacks the typical ene-yne moiety of allylamines or the extented saturated/unsaturated carbon chain of substrate analogs hitherto reported in literature. -(MUSSO*, D. L.; CLARKE, M. J.; KELLEY, J. L.; BOSWELL, G. E.; CHEN, G.; Org. Biomol. Chem 1 (2003) 3, 498-506; GlaxoSmithKline Res. Dev., Research Triangle Park, NC 27709, USA; Eng.) -S. Adam 26-094

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.

Clinical Pharmacology & Therapeutics (2003) 73, P19–P19; doi: