title: The synthesis of 4,7-disubstituted-2H-benzo[b][1,4]-oxazin-3(4H)-ones using Smiles rearrangement and their in vitro evaluation as platelet aggregation inhibitors.
abstract: A series of novel benzo[b][1,4]oxazin-3(4H)-one derivatives were synthesized as platelet aggregation inhibitors for structure-activity relationships (SAR) analysis. The synthetic pattern, involved Smiles rearrangement for the preparation of benzoxazine, was proven to be more efficient than the conventional methods. Biological evaluation demonstrated that among all the synthesized compounds, compound 9u (IC50=9.20μM) exhibited the most potent inhibition activity compared with aspirin, the positive control (IC50=7.07μM). Molecular docking revealed that these set of compounds could be the GPIIb/IIIa antagonist for that they could be situated in the binding site of GPIIb/IIIa receptor quite well.
authors.affiliation: College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Xia
authors.affiliation: College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China.
authors.forename: Ji-Qiang
authors.initials: JQ
authors.lastname: Liu
authors.affiliation: College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China.
authors.forename: Xiu-Hua
authors.initials: XH
authors.lastname: Wang
authors.affiliation: Department of Medicinal Chemistry and Key Laboratory of Chemical Biology, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.affiliation: College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China.
authors.forename: Jing-Huan
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Department of Oncology, The Ninth People's Hospital of Chongqing, Chongqing 400700, China. Electronic address: fangliangfranc@gmail.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Fang
authors.affiliation: College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China. Electronic address: zuohua@swu.edu.cn.
authors.forename: Hua
authors.initials: H
authors.lastname: Zuo
mesh_terms: D048588:Benzoxazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D020134:Catalytic Domain; D062105:Molecular Docking Simulation; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000378:metabolism; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: C000592786:7-((4-benzylpiperazin-1-yl)methyl)-4-propyl-2H-benzo(b)(1,4)oxazin-3(4H)-one; D048588:Benzoxazines; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex
keywords: 4,7-Disubstituted-2H-benzo[b][1,4]oxazin-3(4H)-one; Molecular docking; Platelet aggregation; Smiles rearrangement; Structure–activity relationships (SAR)