2-(4-tert-butylphenyl)-4-(5-methyl-1H-pyrazol-3-ylamino)-2H-phthalazin-1-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2-(4-tert-butylphenyl)-4-(5-methyl-1H-pyrazol-3-ylamino)-2H-phthalazin-1-one
• 英文别名: 2-(4-tert-butylphenyl)-4-[(5-methyl-1H-pyrazol-3-yl)amino]phthalazin-1-one
• 化学式: C₂₂H₂₃N₅O
• 分子量: 373.458
• InChiKey: AIHXCSFEMCZERD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  73.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  对特丁基苯肼盐酸盐 在 tris-(dibenzylideneacetone)dipalladium(0) 、 溶剂黄146 、 2-(二叔丁基膦)联苯 、 sodium t-butanolate 、 三溴氧磷 作用下， 以 乙醇 、 1,2-二氯乙烷 、 甲苯 为溶剂， 反应 40.0h， 生成 2-(4-tert-butylphenyl)-4-(5-methyl-1H-pyrazol-3-ylamino)-2H-phthalazin-1-one
  参考文献：
  名称：

  Phthalazinone Pyrazoles as Potent, Selective, and Orally Bioavailable Inhibitors of Aurora-A Kinase

  摘要：

  The inhibition of Aurora kinases in order to arrest mitosis and subsequently inhibit tumor growth via apoptosis of proliferating cells has generated significant discussion within the literature. We report a novel class of Aurora kinase inhibitors based upon a phthalazinone pyrazole scaffold. The development of the phthalazinone template resulted in a potent Aurora-A selective series of compounds (typically >1000-fold selectivity over Aurora-B) that display good pharmacological profiles with significantly improved oral bioavailability compared to the well studied Aurora inhibitor VX-680.

  DOI：

  10.1021/jm101346r

文献信息

• [EN] NOVEL PHTHALAZINONE DERIVATIVES, AS AURORA-A KINASE INHIBITORS<br/>[FR] NOUVEAUX COMPOSÉS DE PHTALAZINONE SERVANT D'INHIBITEURS DE LA KINASE AURORA-A
  申请人：HOFFMANN LA ROCHE

  公开号：WO2006032518A1

  公开（公告）日：2006-03-30

  Objects of the present invention are the compounds of formula (I) their pharmaceutically acceptable salts, enantiomeric forms, diastereoisomers and racemates, the preparation of the above-mentioned compounds, medicaments containing them and their manufacture, as well as the use of the above-mentioned compounds in the control or prevention of illnesses such as cancer.

  本发明的对象是公式（I）的化合物及其药学上可接受的盐、对映体形式、二对映异构体和消旋体，上述化合物的制备，含有它们的药物以及其制造，以及上述化合物在控制或预防癌症等疾病中的应用。
• Phthalazinone derivatives
  申请人：Boyd Edward

  公开号：US20060089359A1

  公开（公告）日：2006-04-27

  Compounds of formula I their pharmaceutically acceptable salts, enantiomeric forms, diastereoisomers and racemates are disclosed. Also disclosed are methods for the preparation of the above-mentioned compounds, pharmaceutical compositions containing them, as well as the use of the above-mentioned compounds in the treatment, control or prevention of illnesses such as cancer.

  公开了式I的化合物及其药学上可接受的盐、对映体、二对映异构体和混合物。还公开了制备上述化合物的方法、含有它们的药物组合物，以及上述化合物在治疗、控制或预防癌症等疾病中的应用。
• NOVEL PHTHALAZINONE DERIVATIVES, AS AURORA-A KINASE INHIBITORS
  申请人：F.HOFFMANN-LA ROCHE AG

  公开号：EP1794148A1

  公开（公告）日：2007-06-13
• US7226923B2
  申请人：——

  公开号：US7226923B2

  公开（公告）日：2007-06-05
• Phthalazinone Pyrazoles as Potent, Selective, and Orally Bioavailable Inhibitors of Aurora-A Kinase
  作者：Michael E. Prime、Stephen M. Courtney、Frederick A. Brookfield、Richard W. Marston、Victoria Walker、Justin Warne、Andrew E. Boyd、Norman A. Kairies、Wolfgang von der Saal、Anja Limberg、Guy Georges、Richard A. Engh、Bernhard Goller、Petra Rueger、Matthias Rueth

  DOI：10.1021/jm101346r

  日期：2011.1.13

  The inhibition of Aurora kinases in order to arrest mitosis and subsequently inhibit tumor growth via apoptosis of proliferating cells has generated significant discussion within the literature. We report a novel class of Aurora kinase inhibitors based upon a phthalazinone pyrazole scaffold. The development of the phthalazinone template resulted in a potent Aurora-A selective series of compounds (typically >1000-fold selectivity over Aurora-B) that display good pharmacological profiles with significantly improved oral bioavailability compared to the well studied Aurora inhibitor VX-680.