N,N-dialkylated 4-(4-arylsulfonylpiperazine-l-carbonyl)-benzamidines and 4-((4-arylsulfonyl)-2-oxo-piperazin-1-ylmethyl)benzamidines as potent factor Xa inhibitors

被引：17

作者：

Jia, ZJ ^{[1
]}

Su, T ^{[1
]}

Zuckett, JF ^{[1
]}

Wu, YH ^{[1
]}

Goldman, EA ^{[1
]}

Li, WH ^{[1
]}

Zhang, PL ^{[1
]}

Clizbe, LA ^{[1
]}

Song, YH ^{[1
]}

Bauer, SM ^{[1
]}

Huang, WR ^{[1
]}

Woolfrey, J ^{[1
]}

Sinha, U ^{[1
]}

Arfsten, AE ^{[1
]}

Hutchaleelaha, A ^{[1
]}

Hollenbach, SJ ^{[1
]}

Lambing, JL ^{[1
]}

Scarborough, RM ^{[1
]}

Zhu, BY ^{[1
]}

机构：

[1] Millennium Pharmaceut Inc, San Francisco, CA 94080 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 09期

关键词：

factor Xa inhibitors; benzamidines;

D O I：

10.1016/j.bmcl.2004.02.049

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A class of N,N-dialkylated 4-(4-arylsulfonylpiperazine-1-carbonyl)-benzamidines and 4-((4-arylsulfonyl)-2-oxo-pipeRazin-1-y1methyl)-benzamidiries has been discovered as potent factor Xa inhibitors with desirable in vitro and in vivo anticoagulant activity, but with low oral bioavailability. The 5-chloroindole and 6-chlorobenzo[b]thiophene groups are optimal as the factor Xa S1 binding elements. The strategy of incorporating a side chain on the piperazine nucleus to enhance binding affinity has been examined. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：2073 / 2078

页数：6

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