(R)-4-(4-(4-benzoyl-2-methylpiperazin-1-yl)phthalazin-1-yl)benzoic acid | 1245773-21-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (R)-4-(4-(4-benzoyl-2-methylpiperazin-1-yl)phthalazin-1-yl)benzoic acid
• 英文别名: 4-[4-[(2R)-4-benzoyl-2-methylpiperazin-1-yl]phthalazin-1-yl]benzoic acid
• CAS: 1245773-21-0
• 化学式: C₂₇H₂₄N₄O₃
• 分子量: 452.513
• InChiKey: ZYXQNFFWVWSSOK-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  86.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (R)-(4-(4-chlorophthalazin-1-yl)-3-methylpiperazin-1-yl)(phenyl)methanone 、 4-羧基苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 甲苯 为溶剂， 生成 (R)-4-(4-(4-benzoyl-2-methylpiperazin-1-yl)phthalazin-1-yl)benzoic acid
  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

• 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.