Identification of anthranilamide derivatives as potential factor Xa inhibitors Drug design, synthesis and biological evaluation》.pdfVIP

European Journal of Medicinal Chemistry 95 (2015) 388e399 Contents lists available at ScienceDirect European Journal of Medicinal Chemistry journal homepage: http://www.elsevier .com/locate/ejmech Original article Identification of anthranilamide derivatives as potential factor Xa inhibitors: Drug design, synthesis and biological evaluation Junhao Xing a, Lingyun Yang a, Hui Li a, Qing Li a, Leilei Zhao a, Xinning Wang a, Yuan Zhang b, Muxing Zhou a, Jinpei Zhou b, Huibin Zhang a, c, * a Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China b Department of Medicinal Chemistry, China Pharmaceutical University, TongjiaXiang 24, 210009 Nanjing, PR China c Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, Nanjing 210009, PR China a r t i c l e i n f o a b s t r a c t Article history: The coagulation enzyme factor Xa (fXa) plays a crucial role in the blood coagulation cascade. In this Received 11 November 2014 study, three-dimensional fragment based drug design (FBDD) combined with structure-based pharma- Received in revised form cophore (SBP) model and structural consensus docking were employed to identify novel fXa inhibitors. 21 March 2015 After a multi-stage virtual screening (VS) workflow, two hit compounds 3780 and 319 having persistent Accepted 23 March 2015 Available online 25 March 2015 high performance were identified. Then, these two hit compounds and several analogs were synthes