Title of article :
Design, synthesis, and structure–Activity relationships of unsubstituted piperazinone-Based transition state factor Xa inhibitors
Author/Authors :
Wenrong Huang، نويسنده , , Mary Ann Naughton، نويسنده , , Hua Yang، نويسنده , , Ting Su، نويسنده , , Suiko Dam، نويسنده , , Paul W. Wong، نويسنده , , Ann Arfsten، نويسنده , , Susan Edwards، نويسنده , , Uma Sinha، نويسنده , , Stanley Hollenbach، نويسنده , , Robert M. Scarborough، نويسنده , , Bing-Yan Zhu، نويسنده ,
Abstract :
A series of novel transition state factor Xa inhibitors containing a variety of lactam ring systems as central templates was synthesized in an expedient manner and allowed for a great deal of structural variability. Among them, the piperazinone-based inhibitors were found to be not only active against factor Xa but also selective over thrombin. Optimization of the P4 moiety yielded several potent compounds with IC50 below 1 nM against factor Xa.
