(R)-tert-butyl 3-methyl-4-(1-phenylpyrido[3,4-d]pyridazin-4-yl)piperazine-1-carboxylate | 1133748-67-0

• 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)-tert-butyl 3-methyl-4-(1-phenylpyrido[3,4-d]pyridazin-4-yl)piperazine-1-carboxylate
• 英文别名: tert-butyl (3R)-3-methyl-4-(1-phenylpyrido[3,4-d]pyridazin-4-yl)piperazine-1-carboxylate
• CAS: 1133748-67-0
• 化学式: C₂₃H₂₇N₅O₂
• 分子量: 405.5
• InChiKey: QKIFRJGPAPIJEJ-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  71.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (R)-tert-butyl 3-methyl-4-(1-phenylpyrido[3,4-d]pyridazin-4-yl)piperazine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (R)-4-(2-methylpiperazin-1-yl)-1-phenylpyrido[3,4-d]pyridazine
  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
• 作为产物：
  描述：

  (R)-tert-butyl 4-(1-chloropyrido[3,4-d]pyridazin-4-yl)-3-methylpiperazine-1-carboxylate 、 苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 甲苯 为溶剂， 生成 (R)-tert-butyl 3-methyl-4-(1-phenylpyrido[3,4-d]pyridazin-4-yl)piperazine-1-carboxylate
  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

• Pyridopyridazine compounds, compositions and methods of use
  申请人：Kaizerman Jacob

  公开号：US20090099173A1

  公开（公告）日：2009-04-16

  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.

  本发明涉及一般表示为公式I的化合物，包括它们的制药组合物和治疗癌症等疾病或疾病的方法。
• ANNELATED PYRIDAZINES FOR THE TREATMENT OF TUMORS DRIVEN BY INAPPROPRIATE HEDGEHOG SIGNALLING
  申请人：Amgen Inc.

  公开号：EP2188283B1

  公开（公告）日：2012-08-15
• US8222251B2
  申请人：——

  公开号：US8222251B2

  公开（公告）日：2012-07-17
• 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.