179050-10-3Relevant academic research and scientific papers
A novel series of 4-piperidinopyridine and 4-piperidinopyrimidine inhibitors of 2,3-oxidosqualene cyclase-lanosterol synthase
Brown,Hollinshead,Stokes,Waterson,Clarke,Foubister,Glossop,McTaggart,Mirrlees,Smith,Wood
, p. 4964 - 4972 (2007/10/03)
A novel series of 4-piperidinopyridines and 4-piperidinopyrimidines showed potent and selective inhibition of rat 2,3-oxidosqualene cyclase-lanosterol synthase (OSC) (e.g. 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 lower pKa than the corresponding pyridine or the previously reported quinuclidine OSC inhibitor series. This indicates that other novel OSC inhibitors may be found in analogues of this series across a broader pKa range (6.0-9.0). These series may yield novel hypocholesterolemic agents for the treatment of cardiovascular disease.
