Title of article :
Design, synthesis, and SAR of anthranilamide-based factor Xa inhibitors incorporating substituted biphenyl P4 motifs
Author/Authors :
Penglie Zhang، نويسنده , , Liang Bao، نويسنده , , Jingmei F. Zuckett، نويسنده , , Erick A. Goldman، نويسنده , , Zhaozhong J Jia، نويسنده , , Ann Arfsten، نويسنده , , Susan Edwards، نويسنده , , Uma Sinha، نويسنده , , Athiwat Hutchaleelaha، نويسنده , , Gary Park، نويسنده , , Joseph L Lambing، نويسنده , , Stanley J. Hollenbach، نويسنده , , Robert M. Scarborough، نويسنده , , Bing-Yan Zhu، نويسنده ,
Abstract :
Anthranilamides 4 and 5 were designed and synthesized as selective and orally bioavailable factor Xa inhibitors. Structural modifications aimed at lowering their lipophilicity were performed at the central phenyl ring and at the S4 binding biphenyl region by incorporating water solublizing substituents. The resulting compounds (e.g., 7, 8, 14, 30a, and 32b) are highly potent in vitro, and show improved activity in human plasma-based thrombin generation assay.
