6-(1-methyl-1H-pyrazol-4-yl)-2-{3-[5-(2-morpholin-4-yl-ethoxy)-pyrimidin-2-yl]-benzyl}-2H-pyridazin-3-one dihydrogenphosphate | 1232691-18-7

• 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: 6-(1-methyl-1H-pyrazol-4-yl)-2-{3-[5-(2-morpholin-4-yl-ethoxy)-pyrimidin-2-yl]-benzyl}-2H-pyridazin-3-one dihydrogenphosphate
• 英文别名: 6-(1-methylpyrazol-4-yl)-2-[[3-[5-(2-morpholin-4-ylethoxy)pyrimidin-2-yl]phenyl]methyl]pyridazin-3-one;phosphoric acid
• CAS: 1232691-18-7
• 化学式: C₂₅H₂₇N₇O₃*H₃O₄P
• 分子量: 571.53
• InChiKey: ZJLNMCIVKXVBKW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.93
• 重原子数：
  40
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  176
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  6-(1-methyl-1H-pyrazol-4-yl)-2-{3-[5-(2-morpholin-4-yl-ethoxy)-pyrimidin-2-yl]-benzyl}-2H-pyridazin-3-one dihydrogenphosphate 、 以 binary mixture 、 acetonitrile-water 为溶剂， 反应 168.0h， 生成 6-(1-methyl-1H-pyrazol-4-yl)-2-{3-[5-(2-morpholin-4-yl-ethoxy)-pyrimidin-2-yl]-benzyl}-2H-pyridazin-3-one Dihydrogenphosphate Dihydrate
  参考文献：
  名称：

  Polymorphic forms of 6-(1-methyl-1H-pyrazol-4-yl)-2-{3-[5-(2-morpholin-4-yl-ethoxy)-pyrimidin-2-yl]-benzyl}-2H-pyridazin-3-one dihydrogenphosphate and processes of manufacturing thereof

  摘要：

  本发明涉及6-(1-甲基-1H-吡唑-4-基)-2-{3-[5-(2-吗啡啶-4-基-乙氧基)嘧啶-2-基]-苯甲基}-2H-吡啶并[3,2-d][1,3,4]噻二酮二氢磷酸盐、其溶剂化合物和晶体修饰。本发明还涉及制造这些晶体修饰的工艺以及它们在治疗和/或预防由激酶信号转导的抑制、调节和/或调控引起、介导和/或传播的生理和/或病理情况中的使用，特别是通过抑制酪氨酸激酶的抑制，例如癌症等病理情况。

  公开号：

  US08586599B2
• 作为产物：
  描述：

  (4-(2-(2-(3-(3-(1-methyl-1H-pyrazol-4-yl)-6-oxo-1,6-dihydropyridazin-1-ylmethyl)phenyl)pyrimidin-5-yloxy)ethyl)morpholine) 在 磷酸 作用下， 以 水 为溶剂， 生成 6-(1-methyl-1H-pyrazol-4-yl)-2-{3-[5-(2-morpholin-4-yl-ethoxy)-pyrimidin-2-yl]-benzyl}-2H-pyridazin-3-one dihydrogenphosphate
  参考文献：
  名称：

  [EN] NOVEL POLYMORPHIC FORMS OF 6-(1-METHYL-1H-PYRAZOL-4-YL)-2-{3-[5-(2-MORPHOLIN-4-YL-ETHOXY)-PYRIMIDIN-2-YL]-BENZYL}-2H-PYRIDAZIN-3-ONE DIHYDROGENPHOSPHATE AND PROCESSES OF MANUFACTURING THEREOF
  [FR] NOUVEAUX POLYMORPHES DE DIHYDROGÉNOPHOSPHATE DE 6-(1-MÉTHYL-1H-PYRAZOL-4-YL)-2-{3-[5-(2-MORPHOLIN-4-YL-ÉTHOXY)-PYRIMIDIN-2-YL]-BENZYL}-2H-PYRIDAZIN-3-ONE ET PROCÉDÉS DE PRÉPARATION ASSOCIÉS

  摘要：

  本发明涉及6-(1-甲基-1H-吡唑-4-基)-2-{3-[5-(2-吗啉基-4-基-乙氧基)嘧啶-2-基]-苄基}-2H-吡啶并嗪-3-酮二氢磷酸盐、其溶剂结晶体形态的制造方法以及它们在治疗和/或预防由激酶信号传导的抑制、调节和/或调节引起、介导和/或传播的生理和/或病理状况中的使用，特别是通过抑制酪氨酸激酶的抑制，例如癌症等病理状况。

  公开号：

  WO2010072295A1

文献信息

• Novel Polymorphic Forms of 6-(1-methyl-1H-pyrazol-4-yl)-2--2H-pyridazin-3-one Dihydrogenphosphate and Processes of Manufacturing thereof
  申请人：Becker Axel

  公开号：US20110257180A1

  公开（公告）日：2011-10-20

  The present invention relates to 6-(1-methyl-1H-pyrazol-4-yl)-2-3-[5-(2-morpholin-4-yl-ethoxy)-pyrimidin-2-yl]-benzyl}-2H-pyridazin-3-one dihydrogenphosphate, its solvates and crystalline modifications thereof. The present invention further relates to processes of manufacturing these crystalline modifications as well as their use in the treatment and/or prophylaxis of physiological and/or pathophysiological conditions, which are caused, mediated and/or propagated by the inhibition, regulation and/or modulation of signal transduction of kinases, in particular by the inhibition of tyrosine kinases, e.g. pathophysiological conditions such as cancer.

  本发明涉及6-(1-甲基-1H-吡唑-4-基)-2-3-[5-(2-吗啡啉-4-基-乙氧基)嘧啶-2-基]-苄基}-2H-吡啶并[3,2-c][1,2,6]噻二氮磷酸二氢盐、其溶剂化物和晶体修饰。本发明进一步涉及制备这些晶体修饰的方法，以及它们在治疗和/或预防生理和/或病理状态方面的使用，这些状态是由于激酶信号转导的抑制、调节和/或调制所引起、介导和/或传播的，特别是通过抑制酪氨酸激酶的抑制，例如癌症等病理状态。
• NOVEL POLYMORPHIC FORMS OF 6-(1-METHYL-1H-PYRAZOL-4-YL)-2-{3-[5-(2-MORPHOLIN-4-YL-ETHOXY)-PYRIMIDIN-2-YL]-BENZYL}-2H-PYRIDAZIN-3-ONE DIHYDROGENPHOSPHATE AND PROCESSES OF MANUFACTURING THEREOF
  申请人：Merck Patent GmbH

  公开号：EP2361250A1

  公开（公告）日：2011-08-31
• COMPOSITIONS AND METHODS TO IMPROVE THE THERAPEUTIC BENEFIT OF SUBOPTIMALLY ADMINISTERED CHEMICAL COMPOUNDS INCLUDING SUBSTITUTED NAPHTHALIMIDES SUCH AS AMONAFIDE FOR THE TREATMENT OF IMMUNOLOGICAL, METABOLIC, INFECTIOUS, AND BENIGN OR NEOPLASTIC HYPERPROLIFERATIVE DISEASE CONDITIONS
  申请人：BROWN Dennis M.

  公开号：US20160067241A1

  公开（公告）日：2016-03-10

  The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutic agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to naphthalimides such as amonafide or analogs, derivatives, or prodrugs thereof.
• US8586599B2
  申请人：——

  公开号：US8586599B2

  公开（公告）日：2013-11-19
• [EN] NOVEL POLYMORPHIC FORMS OF 6-(1-METHYL-1H-PYRAZOL-4-YL)-2-{3-[5-(2-MORPHOLIN-4-YL-ETHOXY)-PYRIMIDIN-2-YL]-BENZYL}-2H-PYRIDAZIN-3-ONE DIHYDROGENPHOSPHATE AND PROCESSES OF MANUFACTURING THEREOF<br/>[FR] NOUVEAUX POLYMORPHES DE DIHYDROGÉNOPHOSPHATE DE 6-(1-MÉTHYL-1H-PYRAZOL-4-YL)-2-{3-[5-(2-MORPHOLIN-4-YL-ÉTHOXY)-PYRIMIDIN-2-YL]-BENZYL}-2H-PYRIDAZIN-3-ONE ET PROCÉDÉS DE PRÉPARATION ASSOCIÉS
  申请人：MERCK PATENT GMBH

  公开号：WO2010072295A1

  公开（公告）日：2010-07-01

  The present invention relates to 6-(1-methyl-1 H-pyrazol-4-yl)-2-3-[5-(2-morpholin- 4-yl-ethoxy)-pyrimidin-2-yl]-benzyl}-2H-pyridazin-3-one dihydrogenphosphate, its solvates and crystalline modifications thereof. The present invention further relates to processes of manufacturing these crystalline modifications as well as their use in the treatment and/or prophylaxis of physiological and/or pathophysiological conditions, which are caused, mediated and/or propagated by the inhibition, regulation and/or modulation of signal transduction of kinases, in particular by the inhibition of tyrosine kinases, e.g. pathophysiological conditions such as cancer.

  本发明涉及6-(1-甲基-1H-吡唑-4-基)-2-3-[5-(2-吗啉基-4-基-乙氧基)嘧啶-2-基]-苄基}-2H-吡啶并嗪-3-酮二氢磷酸盐、其溶剂结晶体形态的制造方法以及它们在治疗和/或预防由激酶信号传导的抑制、调节和/或调节引起、介导和/或传播的生理和/或病理状况中的使用，特别是通过抑制酪氨酸激酶的抑制，例如癌症等病理状况。