Novel optimised quinuclidine squalene synthase inhibitors

…, S Freeman, F McTaggart, DJ Mirrlees, AC Reid…

Index: Brown, George R.; Foubister, Alan J.; Freeman, Susan; McTaggart, Fergus; Mirrlees, Donald J.; Reid, Alan C.; Smith, Graham J.; Taylor, Melvyn J.; Thomason, Douglas A.; Whittamore, Paul R. O. Bioorganic and Medicinal Chemistry Letters, 1997 , vol. 7, # 5 p. 597 - 600

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Citation Number: 20

Abstract

Optimised quinuclidine squalene synthase (SQS) inhibitors are reported; 3-[2-(2-allyl-4-(2- ethoxy carbonylethyl) phenyl) ethynyl] quinuclidin-3-ol 1c, is a potent inhibitor of rat (KI= 6 nM) and human (KI= 43 nM) microsomal SQS; the oral ED50 of 1c, for the inhibition of rat cholesterol biosynthesis was 1.3±0.45 mg/kg and for the R-enantiomer 1m, 0.8±0.2 mg/kg, with the corresponding R-carboxylic acid 6a, being 0.9±0.25 mg/kg.