Author/Authors :
George R. Brown، نويسنده , , Alan J. Foubister، نويسنده , , Susan Freeman، نويسنده , , Fergus McTaggart، نويسنده , , Donald J. Mirrlees، نويسنده , , Alan C. Reid، نويسنده , , Graham J. Smith، نويسنده , , Melvyn J. Taylor، نويسنده , , Douglas A. Thomason، نويسنده , , Paul R. O. Whittamore، نويسنده ,
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.
