Design, synthesis and structure–activity relationships of benzoxazinone-based factor Xa inhibitors

…, JF Zuckett, L Wang, J Woolfrey, Y Song, ZJ Jia…

Index: Huang, Wenrong; Zhang, Penglie; Zuckett, Jingmei F.; Wang, Lingyan; Woolfrey, John; Song, Yonghong; Jia, Zhaozhong J.; Clizbe, Lane A.; Su, Ting; Tran, Katherine; Huang, Brian; Wong, Paul; Sinha, Uma; Park, Gary; Reed, Andrea; Malinowski, John; Hollenbach, Stanley J.; Scarborough, Robert M.; Zhu, Bing-Yan Bioorganic and Medicinal Chemistry Letters, 2003 , vol. 13, # 3 p. 561 - 566

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Citation Number: 24

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 ...