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 |
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| Affiliation: | 1. College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China;2. Department of Medicinal Chemistry and Key Laboratory of Chemical Biology, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China;3. Department of Oncology, The Ninth People’s Hospital of Chongqing, Chongqing 400700, China;1. Department of Genetics and Microbiology, M. Curie-Sklodowska University, Akademicka 19, 20-033 Lublin, Poland;2. Department of Fish Diseases, National Veterinary Research Institute, Partyzantow 57, 24-100 Pulawy, Poland;1. Laboratory of Pharmacognosy, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan;2. Graduate School of Integrated Arts and Sciences, Hiroshima University, 1-7-1 Kagamiyama, Higashi-hiroshima 739-8521, Japan;1. N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 119991, Russia;2. S.N. Winogradsky Institute of Microbiology, Russian Academy of Sciences, Moscow 117312, Russia;1. Department of Nephropathy, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China;1. G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far East Branch of the Russian Academy of Sciences, Vladivostok, Russia;2. Far Eastern Federal University, Vladivostok, Russia |
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| 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 = 9.20 μM) exhibited the most potent inhibition activity compared with aspirin, the positive control (IC50 = 7.07 μM). 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. |
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| Keywords: | Structure–activity relationships (SAR) Smiles rearrangement Platelet aggregation Molecular docking |
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