Novel 4-piperidinopyridine inhibitors of oxidosqualene cyclase-lanosterol synthase derived by consideration of inhibitor pK(a)

Authors
Brown, GR Foubister, AJ Johnson, MC Newcombe, NJ Waterson, D Wells, SL
Citation
Gr. Brown et al., Novel 4-piperidinopyridine inhibitors of oxidosqualene cyclase-lanosterol synthase derived by consideration of inhibitor pK(a), BIOORG MED, 11(16), 2001, pp. 2213-2216
Citations number
6
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
11
Issue
16
Year of publication
2001
Pages
2213 - 2216
Database
ISI
SICI code
0960-894X(20010820)11:16<2213:N4IOOC>2.0.ZU;2-W
Abstract
Potent inhibition of rat microsomal oxidosqualene cyclase-lanosterol syntha se (OSC) was maintained after structural modification of the 4-piperidinopy ridine 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 ED80 0.7 mg/kg), and diminished effects on rat feeding after a 100 mg/k g oral dose. (C) 2001 Elsevier Science Ltd. All rights reserved.