Design,synthesis and biological evaluation of dihydroquinoxalinone derivatives as BRD4 inhibitors |
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| Affiliation: | 1. Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China;2. Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China;1. State Key Lab of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, China;2. Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences ,345 Lingling Road, Shanghai 200032 China;3. State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China |
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| Abstract: | BRD4 plays a key role in transcriptional regulation. Recent biological and pharmacological studies have demonstrated that bromodomain-containing protein 4 (BRD4) is a viable drug target for cancer treatment. In this study, we synthesized a series of dihydroquinoxalinone derivatives and evaluated their BRD4 inhibitory activities, obtaining compound 5i with IC50 value of 73 nM of binding activity in BRD4(1) and 258 nM of cellular activity in MV-4-11 cancer cell lines. Docking studies were performed to explain the structure-activity relationship. Based on its potent biochemical and anti-proliferative activity, the novel BRD4 inhibitor compound 5i, is a promising lead compound for further investigation. |
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| Keywords: | BRD4 inhibitors Cancer Molecular docking Dihydroquinoxalinone derivatives |
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