A novel series of 4-piperidinopyridine and 4-piperidinopyrimidine inhibitors of 2, 3-oxidosqualene cyclase-lanosterol synthase

…, AJ Foubister, SC Glossop, F McTaggart…

Index: Brown; Hollinshead; Stokes; Waterson; Clarke; Foubister; Glossop; McTaggart; Mirrlees; Smith; Wood Journal of Medicinal Chemistry, 2000 , vol. 43, # 26 p. 4964 - 4972

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Citation Number: 20

Abstract

A novel series of 4-piperidinopyridines and 4-piperidinopyrimidines showed potent and selective inhibition of rat 2, 3-oxidosqualene cyclase-lanosterol synthase (OSC)(eg 26 IC50 rat= 398±25 nM, human= 112±25 nM) and gave selective oral inhibition of rat cholesterol biosynthesis (26 ED80= 1.2±0.3 mg/kg, n= 5; HMGCoA reductase inhibitor simvastatin ED80= 1.2±0.3 mg/kg, n= 5). The piperidinopyrimidine OSC inhibitors have a significantly ...