Author/Authors :
Wenrong Huang، نويسنده , , Penglie Zhang، نويسنده , , Jingmei F. Zuckett، نويسنده , , Lingyan Wang، نويسنده , , John Woolfrey، نويسنده , , Yonghong Song، نويسنده , , Zhaozhong J. Jia، نويسنده , , Lane A. Clizbe، نويسنده , , Ting Su، نويسنده , , Katherine Tran، نويسنده , , Brian Huang، نويسنده , , Paul Wong، نويسنده , , Uma Sinha، نويسنده , , Gary Park، نويسنده , , Andrea Reed، نويسنده , , John Malinowski، نويسنده , , Stanley J. Hollenbach، نويسنده , , Robert M. Scarborough، نويسنده , , Bing-Yan Zhu، نويسنده ,
Abstract :
A series of benzoxazinone derivatives was designed and synthesized as factor Xa inhibitors. We demonstrated that the naphthyl moiety in the aniline-based compounds 1 and 2 can be replaced with benzene-fused heterobicycles and biaryls to give factor Xa inhibitors with improved trypsin selectivity. The P4 modifications lead to monoamidines which are moderately active. The benzoxazinones 41–45 are potent against factor Xa, retain the improved trypsin selectivity of the corresponding aniline-based compounds, and show strong antithrombotic effect dose responsively.
