A NOVEL FACTOR XA INHIBITOR - STRUCTURE-ACTIVITY-RELATIONSHIPS AND SELECTIVITY BETWEEN FACTOR XA AND THROMBIN

被引：53

作者：

KATAKURA, S

NAGAHARA, T

HARA, T

IWAMOTO, M

机构：

[1] Exploratory Research Laboratories 2, Daiichi Pharmaceutical Co. Ltd., Tokyo 134, 1-16-13 Kita-Kasai, Edogawa-ku

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1993年 / 197卷 / 02期

关键词：

D O I：

10.1006/bbrc.1993.2573

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：

A series of 3-amidinoaryl-2-[4-[[(3S)-3-pyrrolidinyl]oxy]phenyl] propanoic acids have been investigated for development of a novel factor Xa inhibitor, possessing a potent inhibitory activity for factor Xa and a selectivity for factor Xa compared to thrombin. In order to study the structure-activity relationships and the selectivity, models of factor Xa complexes formed with the inhibitors were constructed on the basis of X-ray crystallographic data of a trypsin-inhibitor complex. The models showed that the binding mode of the inhibitors to the S1 pocket of the enzyme accounted for the structure- activity relationships and that the difference between Gln192 of factor Xa and Glu192 of thrombin had a key role in the selectivity. © 1993 Academic Press, Inc.

引用

页码：965 / 972

页数：8

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