Novel optimised quinuclidine squalene synthase inhibitors

被引：21

作者：

Brown, GR

Foubister, AJ

Freeman, S

McTaggart, F

Mirrlees, DJ

Reid, AC

Smith, GJ

Taylor, MJ

Thomason, DA

Whittamore, PRO

机构：

[1] Cardiovasc./Muscoskeletal Res. Dept., Zeneca Pharmaceuticals, Macdesfield, Cheshire SK10 4TG, Alderley Park

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1997年 / 7卷 / 05期

关键词：

CORONARY-HEART-DISEASE; SYNTHETASE;

D O I：

10.1016/S0960-894X(97)00053-X

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Optimised quinuclidine squalene synthase (SQS) inhibitors are reported; 3-[2-(2-allyl-4-(2-ethoxy carbonylethyl)phenyl)ethynyl]quinuclidin-3-ol 1c, is a potent inhibitor of rat (KI = 6 nM) and human (KI = 43 nM) microsomal SQS; the oral ED(50) of 1c, for the inhibition of rat cholesterol biosynthesis was 1.3+/-0.45 mg/kg and for the R-enantiomer 1m, 0.8+/-0.2 mg/kg, with the corresponding R-carboxylic acid 6a, being 0.9+/-0.25 mg/kg. (C) 1997 Elsevier Science Ltd. All rights reserved.

引用

页码：597 / 600

页数：4

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