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Bioorg Med Chem Lett ; 11(16): 2213-6, 2001 Aug 20.
Article in English | MEDLINE | ID: mdl-11514173

ABSTRACT

Potent inhibition of rat microsomal oxidosqualene cyclase-lanosterol synthase (OSC) was maintained after structural modification of the 4-piperidinopyridine OSC inhibitor series. These novel analogues with a much lower pK(a) range (5.8-6.7) gave potent oral inhibition of rat cholesterol biosynthesis (8 ED(80) 0.7 mg/kg), and diminished effects on rat feeding after a 100 mg/kg oral dose.


Subject(s)
Enzyme Inhibitors/pharmacology , Intramolecular Transferases/antagonists & inhibitors , Piperidines/chemical synthesis , Pyridines/chemical synthesis , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Intramolecular Transferases/metabolism , Kinetics , Piperidines/chemistry , Piperidines/pharmacology , Pyridines/chemistry , Pyridines/pharmacology
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