Transformation of a selective factor Xa inhibitor rivaroxaban into a dual factor Xa/thrombin inhibitor by modification of the morpholin-3-one moiety

被引：7
|
作者：
Trstenjak, Uros [1 ]
Ilas, Janez [1 ]
Kikelj, Danijel [1 ]
机构：
[1] Univ Ljubljana, Fac Pharm, Ljubljana 1000, Slovenia
来源：
MEDCHEMCOMM | 2014年 / 5卷 / 02期
关键词：
PLATELET-AGGREGATION; THROMBIN; DISCOVERY; POTENT; WEIGHT; DESIGN; SERIES;
D O I：
10.1039/c3md00250k
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：
Replacement of the P-4 morpholin-3-one moiety in a selective factor Xa inhibitor rivaroxaban by 2-ethoxycarbonylpiperidine resulted in a dual factor Xa/thrombin inhibitor 24, possessing a K-i of 62 +/- 18 nM for factor Xa and a K-i of 353 +/- 75 nM for thrombin. Presented rationalization of dual activity provides a good starting point for "designing in" thrombin inhibitory activity to potent factor Xa inhibitor rivaroxaban.
引用
收藏
页码：197 / 202
页数：6
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