((R)-4-(4-(1H-indol-1-yl)phthalazin-1-yl)-3-methylpiperazin-1-yl)(phenyl)methanone | 1095638-83-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: ((R)-4-(4-(1H-indol-1-yl)phthalazin-1-yl)-3-methylpiperazin-1-yl)(phenyl)methanone
• 英文别名: (R)-(4-(4-(indolin-1-yl)phthalazin-1-yl)-3-methylpiperazin-1-yl)(phenyl)methanone；[(3R)-4-(4-indol-1-ylphthalazin-1-yl)-3-methylpiperazin-1-yl]-phenylmethanone
• CAS: 1095638-83-7
• 化学式: C₂₈H₂₅N₅O
• 分子量: 447.539
• InChiKey: QOWBMSKVQFFCNY-HXUWFJFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  34
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  54.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  吲哚 、 (R)-(4-(4-chlorophthalazin-1-yl)-3-methylpiperazin-1-yl)(phenyl)methanone 在 copper(l) iodide 、 phosphate potassium salt 、 反式-1,2-环己二胺 作用下， 以 1,4-二氧六环 为溶剂， 生成 ((R)-4-(4-(1H-indol-1-yl)phthalazin-1-yl)-3-methylpiperazin-1-yl)(phenyl)methanone
  参考文献：
  名称：

  Addressing PXR liabilities of phthalazine-based hedgehog/smoothened antagonists using novel pyridopyridazines

  摘要：

  Pyridopyridazine antagonists of the hedgehog signaling pathway are described. Designed to optimize our previously described phthalazine smoothened antagonists, a representative compound eliminates a PXR liability while retaining potency and in vitro metabolic stability. Moreover, the compound has improved efficacy in a hedgehog/smoothened signaling mouse pharmacodynamic model. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.06.006

文献信息

• Phthalazine compounds, compositions and methods of use
  申请人：Austin Richard J.

  公开号：US20090048259A1

  公开（公告）日：2009-02-19

  The present invention relates generally to compounds represented in Formula I, pharmaceutical compositions comprising them and methods of treating of diseases or disorders such as cancer.

  本发明一般涉及在式I中表示的化合物，包括它们的药物组合物以及治疗癌症等疾病或疾病的方法。
• PHTHALAZINE COMPOUNDS, COMPOSITIONS AND METHODS OF USE
  申请人：Amgen Inc.

  公开号：EP2170866B1

  公开（公告）日：2014-08-13
• US8153633B2
  申请人：——

  公开号：US8153633B2

  公开（公告）日：2012-04-10
• [EN] PHTHALAZINE COMPOUNDS, COMPOSITIONS AND METHODS OF USE<br/>[FR] COMPOSÉS DE PHTHALAZINE, COMPOSITIONS ET PROCÉDÉS D'UTILISATION
  申请人：AMGEN INC

  公开号：WO2009002469A1

  公开（公告）日：2008-12-31

  [EN] The present invention relates generally to compounds represented in Formula I, pharamaceutical compositions comprising them and methods of treating of diseases or disorders such as cancer.
  [FR] La présente invention concerne de manière générale des composés représentés par la formule I, des compositions pharmaceutiques contenant ceux-ci et des procédés destinés à traiter des maladies ou des troubles tels que le cancer.
• Addressing PXR liabilities of phthalazine-based hedgehog/smoothened antagonists using novel pyridopyridazines
  作者：Jacob A. Kaizerman、Wade Aaron、Songzhu An、Richard Austin、Matt Brown、Angela Chong、Tom Huang、Randall Hungate、Ben Jiang、Michael G. Johnson、Gary Lee、Brian S. Lucas、Jessica Orf、Minqing Rong、Maria M. Toteva、Dineli Wickramasinghe、Guifen Xu、Qiuping Ye、Wendy Zhong、Dustin L. McMinn

  DOI：10.1016/j.bmcl.2010.06.006

  日期：2010.8

  Pyridopyridazine antagonists of the hedgehog signaling pathway are described. Designed to optimize our previously described phthalazine smoothened antagonists, a representative compound eliminates a PXR liability while retaining potency and in vitro metabolic stability. Moreover, the compound has improved efficacy in a hedgehog/smoothened signaling mouse pharmacodynamic model. (C) 2010 Elsevier Ltd. All rights reserved.