title: 6,7-Dihydrobenzo[f]benzo[4,5]imidazo[1,2-d][1,4]oxazepine derivatives as selective inhibitors of PI3Kα.
abstract: Twenty eight 6,7-dihydrobenzo[f]benzo[4,5]imidazo[1,2-d][1,4]oxazepine derivatives were synthesized and evaluated their biological activities as PI3K inhibitors. Biological evaluation against four human tumor cell lines revealed that most target compounds showed impressively better antiproliferative activities than that of LY294002. Among these compounds, compound 25 exhibited the most potent and selective activity for PI3Kα, with the IC50 value of 0.016μM, an approximately 30-fold increase in comparison with LY294002, it also has an increased potency of approximately 11-fold for PI3Kβ. It indicated the potential of developing 6,7-dihydrobenzo[f]benzo[4,5]imidazo[1,2-d][1,4]oxazepine derivatives as the new PI3Kα selective inhibitors for tumor treatment.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Biao
authors.initials: B
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Shao
authors.initials: S
authors.lastname: Sha
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Xun
authors.initials: X
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Chetan B
authors.initials: CB
authors.lastname: Sangani
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: She-Feng
authors.initials: SF
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Qiao
authors.affiliation: College of Science, Nanjing Agriculture University, Nanjing 210095, People's Republic of China.
authors.forename: Ai-Min
authors.initials: AM
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Peng-Cheng
authors.initials: PC
authors.lastname: Lv
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China. Electronic address: zhuhl@nju.edu.cn.
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D058534:Class I Phosphatidylinositol 3-Kinases; D004305:Dose-Response Relationship, Drug; D045325:HCT116 Cells; D018922:HL-60 Cells; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010077:Oxazepines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D006576:Heterocyclic Compounds, 4 or More Rings; D010077:Oxazepines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; C484760:PIK3CA protein, human
keywords: 6,7-Dihydrobenzo[f]benzo[4,5]imidazo[1,2-d][1,4]oxazepine derivatives; Antitumor; PI3Kα