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
相关论文
共 50 条
  • [1] Rivaroxaban: An Oral Factor Xa Inhibitor
    Thomas, Tyan F.
    Ganetsky, Valerie
    Spinier, Sarah A.
    CLINICAL THERAPEUTICS, 2013, 35 (01) : 4 - 27
  • [2] The direct factor Xa inhibitor rivaroxaban
    Verma, Abhishek K.
    Brighton, Timothy A.
    MEDICAL JOURNAL OF AUSTRALIA, 2009, 190 (07) : 379 - 383
  • [3] Rivaroxaban: An oral direct inhibitor of factor Xa
    Gulseth, Michael P.
    Michaud, Jessica
    Nutescu, Edith A.
    AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY, 2008, 65 (16) : 1520 - 1529
  • [4] Rivaroxaban, an oral direct factor Xa inhibitor
    Piccini, Jonathan P.
    Patel, Manesh R.
    Mahaffey, Kenneth W.
    Fox, Keith A. A.
    Califf, Robert M.
    EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2008, 17 (06) : 925 - 937
  • [5] Rivaroxaban: A New Oral Factor Xa Inhibitor
    Perzborn, Elisabeth
    Roehrig, Susanne
    Straub, Alexander
    Kubitza, Dagmar
    Mueck, Wolfgang
    Laux, Volker
    ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2010, 30 (03) : 376 - U24
  • [6] Rivaroxaban.: Factor Xa inhibitor, anticoagulant.
    Escolar, G.
    Villalta, J.
    Casals, F.
    Bozzo, J.
    Serradell, N.
    Bolos, J.
    DRUGS OF THE FUTURE, 2006, 31 (06) : 484 - 493
  • [7] Rivaroxaban: A Novel, Oral, Direct Factor Xa Inhibitor
    Abrams, Paris J.
    Emerson, Christopher R.
    PHARMACOTHERAPY, 2009, 29 (02): : 167 - 181
  • [8] Rivaroxaban, the first oral, direct factor Xa inhibitor
    Fassiadis, Nicholas
    EXPERT OPINION ON PHARMACOTHERAPY, 2009, 10 (18) : 2945 - 2946
  • [9] RIVAROXABAN, A DIRECT FACTOR XA INHIBITOR: A DRUG UPDATE
    Shyamasakhi, P. D.
    Sania, K. M.
    Meena, N. D.
    Bikram, T.
    Tarinita, L.
    INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES AND RESEARCH, 2015, 6 (08): : 3186 - 3191
  • [10] Inhibition of thrombin generation in human plasma by rivaroxaban, an oral, direct Factor Xa inhibitor
    Perzborn, E.
    Harwardt, M.
    JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2009, 7 : 379 - 379
12345