Synthesis and biological evaluation of novel propylamine derivatives as orally active squalene synthase inhibitors

被引：22
|
作者：
Ishihara, T [1 ]
Kakuta, H [1 ]
Moritani, H [1 ]
Ugawa, T [1 ]
Yanagisawa, I [1 ]
机构：
[1] Yamanouchi Pharmaceut Co Ltd, Inst Drug Discovery Res, Chem Labs, Tsukuba, Ibaraki 3058585, Japan
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2004年 / 12卷 / 22期
关键词：
squalene synthase; antihypercholesterolemic effect; antihypertriglyceridemic effect; hepatotoxicity;
D O I：
10.1016/j.bmc.2004.08.033
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Squalene synthase inhibitors are potentially superior hypolipidemic agents. We synthesized novel propylamine derivatives, as well as evaluated their ability to inhibit squalene synthase and their lipid-lowering effects in rats. 1-Allyl-2-[3-(benzylamino)propoxy]-9H-carbazole (YM-75440) demonstrated potent inhibition of the enzyme derived from HepG2 cells with an IC50 value of 63nM. It significantly reduced both plasma total cholesterol and plasma triglyceride levels following oral dosing to rats with a reduced tendency to elevate plasma transaminase levels. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码：5899 / 5908
页数：10
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