title: Novel Anthranilamide-Based FXa Inhibitors: Drug Design, Synthesis and Biological Evaluation.
abstract: Factor Xa (FXa) plays a significant role in the blood coagulation cascade and it has become a promising target for anticoagulation drugs. Three oral direct FXa inhibitors have been approved by the FDA for treating thrombotic diseases. By structure-activity relationship (SAR) analysis upon these FXa inhibitors, a series of novel anthranilamide-based FXa inhibitors were designed and synthesized. According to our study, compounds 1a, 1g and 1s displayed evident FXa inhibitory activity and excellent selectivity over thrombin in in vitro inhibition activities studies. Compounds 1g and 1s also exhibited pronounced anticoagulant activities in in vitro anticoagulant activity studies.
authors.affiliation: School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China. wangwenzhi870507@163.com.|Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China. wangwenzhi870507@163.com.
authors.forename: Wenzhi
authors.initials: W
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China. yuanj@tjipr.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China. fuxl@tjipr.com.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Fu
authors.affiliation: Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China. mengfc@tjipr.com.
authors.forename: Fancui
authors.initials: F
authors.lastname: Meng
authors.affiliation: Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China. zhangsj@tjipr.com.
authors.forename: Shijun
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China. xuwr@tjipr.com.
authors.forename: Weiren
authors.initials: W
authors.lastname: Xu
authors.affiliation: School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China. wzzyyx2016@163.com.
authors.forename: Yongnan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China. huangcj@tjipr.com.
authors.forename: Changjiang
authors.initials: C
authors.lastname: Huang
mesh_terms: D000925:Anticoagulants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D018360:Crystallography, X-Ray; D015195:Drug Design; D015951:Factor Xa / Q000737:chemistry* / Q000378:metabolism; D065427:Factor Xa Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D000069552:Rivaroxaban / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000737:chemistry; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy*; D062367:ortho-Aminobenzoates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D062367:ortho-Aminobenzoates; D000069552:Rivaroxaban; D013917:Thrombin; D015951:Factor Xa; C000219:anthranilamide
keywords: FXa inhibitor; anthranilamide-based FXa inhibitors; docking simulation; thrombosis