2-{(R)-4-[6-(2,4-difluoro-benzyl)-4,5-dimethyl-pyridazin-3-yl]-2-methyl-piperazin-1-yl}-4-trifluoromethyl-pyrimidine-5-carboxylic acid ethyl ester | 1204975-08-5

• 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: 2-{(R)-4-[6-(2,4-difluoro-benzyl)-4,5-dimethyl-pyridazin-3-yl]-2-methyl-piperazin-1-yl}-4-trifluoromethyl-pyrimidine-5-carboxylic acid ethyl ester
• 英文别名: ethyl 2-[(2R)-4-[6-[(2,4-difluorophenyl)methyl]-4,5-dimethylpyridazin-3-yl]-2-methylpiperazin-1-yl]-4-(trifluoromethyl)pyrimidine-5-carboxylate
• CAS: 1204975-08-5
• 化学式: C₂₆H₂₇F₅N₆O₂
• 分子量: 550.531
• InChiKey: DYGCINYUEKOJBJ-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  39
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  84.3
• 氢给体数：
  0
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  2-{(R)-4-[6-(2,4-difluoro-benzyl)-4,5-dimethyl-pyridazin-3-yl]-2-methyl-piperazin-1-yl}-4-trifluoromethyl-pyrimidine-5-carboxylic acid ethyl ester 、 甲基溴化镁 在 水 、 氯化铵 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 0.5h， 以13%的产率得到2-(2-{(R)-4-[6-(2,4-difluoro-benzyl)-4,5-dimethyl-pyridazin-3-yl]-2-methyl-piperazin-1-yl}-4-trifluoromethyl-pyrimidin-5-yl)-propan-2-ol
  参考文献：
  名称：

  Organic Compounds as Smo Inhibitors

  摘要：

  本发明一般涉及与Hedgehog通路相关的病理诊断和治疗的新化合物，包括但不限于肿瘤形成、癌症、肿瘤和非恶性过度增殖性疾病。本发明包括新化合物、新组合物、它们的使用方法和制备方法，这些化合物通常在药理学上作为治疗剂是有用的，其作用机制涉及通过抑制Hedgehog和Smo信号通路的方法来抑制肿瘤发生、肿瘤生长和肿瘤存活。

  公开号：

  US20100041663A1
• 作为产物：
  描述：

  2-[(R)-4-(6-chloro-4,5-dimethyl-pyridazin-3-yl)-2-methyl-piperazin-1-yl]-4-trifluoromethyl-pyrimidine-5-carboxylic acid ethyl ester 、 bromozinc(1+),2,4-difluoro-1-methanidylbenzene 在 四(三苯基膦)钯 水 、 乙酸乙酯 、 magnesium sulfate 、 silica gel 、 ethyl acetate heptane 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以to yield the desired compound (225 mg, 81%)的产率得到2-{(R)-4-[6-(2,4-difluoro-benzyl)-4,5-dimethyl-pyridazin-3-yl]-2-methyl-piperazin-1-yl}-4-trifluoromethyl-pyrimidine-5-carboxylic acid ethyl ester
  参考文献：
  名称：

  Pyridazinyl derivatives as smo inhibitors

  摘要：

  本发明涉及公式I的化合物：其中R11和R12在发明摘要中定义; 能够抑制Hedgehog和Smo信号通路。本发明还提供了制备本发明化合物的方法，包括这些化合物的制药制剂以及使用这些化合物和组合物在诊断和治疗与Hedgehog和Smo信号通路相关的病理学，例如肿瘤形成，癌症，肿瘤和非恶性增生性疾病。

  公开号：

  US08481542B2

文献信息

• [EN] PYRIDAZINE DERIVATIVES AS SMO INHIBITORS<br/>[FR] DÉRIVÉS DE PYRIDAZINE EN TANT QU'INHIBITEURS DE SMO
  申请人：NOVARTIS AG

  公开号：WO2010007120A1

  公开（公告）日：2010-01-21

  The present invention relates generally to novel compounds relating to the diagnosis and treatment of pathologies relating to the Hedgehog pathway, including but not limited to tumor formation, cancer, neoplasia, and non-malignant hyperproliferative disorders. The present invention includes novel compounds, novel compositions, methods of their use and methods of their manufacture, where such compounds are generally pharmacologically useful as agents in therapies whose mechanism of action involve methods of inhibiting tumorigenesis, tumor growth and tumor survival using agents that inhibit the Hedgehog and Smo signaling pathway.

  本发明涉及与Hedgehog通路相关的病理诊断和治疗的新化合物，包括但不限于肿瘤形成、癌症、肿瘤新生和非恶性高增殖性疾病。本发明包括新的化合物、新的组合物、它们的使用方法和制造方法，其中这些化合物通常作为药理学上有用的治疗剂，其作用机制涉及使用抑制Hedgehog和Smo信号通路的剂量来抑制肿瘤发生、肿瘤生长和肿瘤存活的方法。
• ORGANIC COMPOUNDS AS SMO INHIBITORS
  申请人：HE Feng

  公开号：US20120289507A1

  公开（公告）日：2012-11-15

  The present invention relates generally to novel compounds relating to the diagnosis and treatment of pathologies relating to the Hedgehog pathway, including but not limited to tumor formation, cancer, neoplasia, and non-malignant hyperproliferative disorders. The present invention includes novel compounds, novel compositions, methods of their use and methods of their manufacture, where such compounds are generally pharmacologically useful as agents in therapies whose mechanism of action involve methods of inhibiting tumorigenesis, tumor growth and tumor survival using agents that inhibit the Hedgehog and Smo signaling pathway.

  本发明涉及与Hedgehog通路相关的病理诊断和治疗的新化合物，包括但不限于肿瘤形成、癌症、肿瘤新生和非恶性过度增殖性疾病。本发明包括新化合物、新组合物、它们的使用方法和制备方法，这些化合物通常在药理学上可用作抑制肿瘤发生、肿瘤生长和肿瘤存活的治疗剂，其机制涉及抑制Hedgehog和Smo信号通路的方法。
• Pyridazinyl derivatives as smo inhibitors
  申请人：He Feng

  公开号：US08481542B2

  公开（公告）日：2013-07-09

  The present invention relates to compounds of formula I: in which R11 and R12 are defined in the Summary of the Invention; capable of inhibiting the Hedgehog and Smo signaling pathway. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds and compositions in the diagnosis and treatment of pathologies relating to the Hedgehog and Smo signaling pathway, for example, tumor formation, cancer, neoplasia and non-malignant hyperproliferative disorders.

  本发明涉及公式I的化合物：其中R11和R12在发明摘要中定义; 能够抑制Hedgehog和Smo信号通路。本发明还提供了制备本发明化合物的方法，包括这些化合物的制药制剂以及使用这些化合物和组合物在诊断和治疗与Hedgehog和Smo信号通路相关的病理学，例如肿瘤形成，癌症，肿瘤和非恶性增生性疾病。
• PYRIDAZINYL DERIVATIVES AS SMO INHIBITORS
  申请人：He Feng

  公开号：US20130261299A1

  公开（公告）日：2013-10-03

  The present invention relates to compounds of formula I: in which L, W, X, Y, Z, m, p, R1, R2, R3, R4 and R7 are defined in the Summary of the Invention; capable of inhibiting the Hedgehog and Smo signaling pathway. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds and compositions in the diagnosis and treatment of pathologies relating to the Hedgehog and Smo signaling pathway, for example, tumor formation, cancer, neoplasia and non-malignant hyperproliferative disorders.

  本发明涉及式I的化合物：其中L、W、X、Y、Z、m、p、R1、R2、R3、R4和R7在发明摘要中被定义；能够抑制Hedgehog和Smo信号通路。本发明还提供了一种制备本发明化合物的方法，包括含有这种化合物的制药制剂以及在与Hedgehog和Smo信号通路相关的病理学诊断和治疗中使用这种化合物和组合物的方法，例如肿瘤形成、癌症、肿瘤新生和非恶性增殖性疾病。
• PYRIDAZINE DERIVATIVES AS SMO INHIBITORS
  申请人：Novartis AG

  公开号：EP2318389A1

  公开（公告）日：2011-05-11