Novel 4-piperidinopyridine inhibitors of oxidosqualene cyclase-lanosterol synthase derived by consideration of inhibitor pKa

被引：10

作者：

Brown, GR ^{[1
]}

Foubister, AJ ^{[1
]}

Johnson, MC ^{[1
]}

Newcombe, NJ ^{[1
]}

Waterson, D ^{[1
]}

Wells, SL ^{[1
]}

机构：

[1] AstraZeneca, Macclesfield SK10 4TG, Cheshire, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 16期

关键词：

D O I：

10.1016/S0960-894X(01)00423-1

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 ED80 0.7 mg/kg), and diminished effects on rat feeding after a 100 mg/kg oral dose. (C) 2001 Elsevier Science Ltd. All rights reserved.

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页码：2213 / 2216

页数：4

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