Title of article :
Design, synthesis, and SAR of anthranilamide-based factor Xa inhibitors with improved functional activity
Author/Authors :
Penglie Zhang، نويسنده , , Liang Bao، نويسنده , , Jingmei F. Zuckett، نويسنده , , Zhaozhong J. Jia، نويسنده , , John Woolfrey، نويسنده , , Ann Arfsten، نويسنده , , Susan Edwards، نويسنده , , Uma Sinha، نويسنده , , Athiwat Hutchaleelaha، نويسنده , , Joseph L. Lambing، نويسنده , , Stanley J. Hollenbach، نويسنده , , Robert M. Scarborough، نويسنده , , Bing-Yan Zhu، نويسنده ,
Abstract :
Compound 2 containing an aminomethylbenzoyl moiety as the S4 binding motif was synthesized in order to modulate hydrophlicity of anthranilamide-based factor Xa inhibitors with substituted biphenyl P4 groups. Structure–activity relationship studies around 2 have led to a series of potent factor Xa inhibitors which are highly active in the human plasma-based thrombin generation assay with 2XTG values less than 1 μM. Compound 55 shows strong antithrombotic activity in our rabbit deep vein thrombosis model, and also exhibits good oral bioavailability and a long half life in rats.
