methyl (3Z)-3-{[(4-{methyl[(4-methylpiperazin-1-yl)acetyl]amino}phenyl)amino](phenyl)methylidene}-2-oxo-2,3-dihydro-1H-indole-6-carboxylate phosphoric acid salt | 959761-75-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: methyl (3Z)-3-{[(4-{methyl[(4-methylpiperazin-1-yl)acetyl]amino}phenyl)amino](phenyl)methylidene}-2-oxo-2,3-dihydro-1H-indole-6-carboxylate phosphoric acid salt
• 英文别名: intedanib phosphoric acid salt；3-Z-[1-(4-(N-((4-methyl-piperazin-1-yl)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone phosphate；methyl (3Z)-3-[[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]anilino]-phenylmethylidene]-2-oxo-1H-indole-6-carboxylate;phosphoric acid
• CAS: 959761-75-2
• 化学式: C₃₁H₃₃N₅O₄*H₃O₄P
• 分子量: 637.629
• InChiKey: IFKJBAKESVSNBI-FJBFXRHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.69
• 重原子数：
  45.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  171.98
• 氢给体数：
  5.0
• 氢受体数：
  8.0

反应信息

• 作为产物：
  描述：

  尼达尼布 在 磷酸 作用下， 以 丙酮 为溶剂， 反应 72.0h， 生成 methyl (3Z)-3-{[(4-{methyl[(4-methylpiperazin-1-yl)acetyl]amino}phenyl)amino](phenyl)methylidene}-2-oxo-2,3-dihydro-1H-indole-6-carboxylate phosphoric acid salt
  参考文献：
  名称：

  SPECIALLY FORMULATED COMPOSITIONS OF INHALED NINTEDANIB AND NINTEDANIB SALTS

  摘要：

  本文公开了尼特丹尼布及其盐、吲哚酮衍生物化合物及其盐的配方，用于喷雾剂，并使用这些配方预防或治疗各种纤维化、致癌、血管和病毒感染性疾病，包括与肺部、心脏、肾脏、肝脏、眼睛、中枢神经系统和手术部位相关的疾病。本文所描述的配方和传递选项允许有效地局部传递尼特丹尼布或吲哚酮衍生物化合物或其盐。方法包括吸入程序、适应症和制造过程，用于生产和使用所述的组合物。还包括识别通过重新配制和吸入给药获益的化合物和适应症的方法。

  公开号：

  US20200060968A1

文献信息

• [EN] CRYSTALLINE MODIFICATIONS OF METHYL (3Z)-3-{[(4-{METHYL[(4-METHYLPIPERAZIN-1-YL)ACETYL]AMINO} PHENYL)AMINO](PHENYL)METHYLIDENE}-2-OXO-2,3-DIHYDRO-1H-INDOLE-6-CARBOXYLATE SALTS AND METHODS OF PREPARATION THEREOF<br/>[FR] MODIFICATIONS CRISTALLINES DE SELS (3Z)-3-{[(4-{MÉTHYL[(4-MÉTHYLPIPÉRAZIN-1-YL)ACÉTYL]AMINO}PHÉNYL)AMINO](PHÉNYL)MÉTHYLIDÈNE}-2-OXO-2,3-DIHYDRO-1H-INDOLE-6-CARBOXYLATE DE MÉTHYLE ET LEURS PROCÉDÉS DE PRÉPARATION
  申请人：ZENTIVA KS

  公开号：WO2017144029A1

  公开（公告）日：2017-08-31

  The present solution relates to crystalline modifications of methyl (3Z)-3-[(4-methyl[(4- methylpiperazin-l-yl)acetyl]amino}phenyl)amino](phenyl)methylidene}-2-oxo-2,3-dihydro-lH-indole- 6-carboxylate salts of Formula I, wherein HX represents at least one acid component, preferably methanesulfonic acid, p-toluenesulphonic acid, L-tartaric acid, maleic acid, acetic acid and phosphoric acid. Another solution also relates to the processes for the preparation thereof as well as said use thereof in phamaceutically acceptable compositions. Use of said crystalline forms of intedanib and manufactured salts in the preparation of methyl (3Z)-3-[(4-methyl[(4-methylpiperazin-l- yl)acetyl]amino}phenyl)amino](phenyl)methylidene}-2-oxo-2,3-dihydro-lH-indole-6-carboxylate in the form of any phamaceutically acceptable salt thereof is also object of this invention.

  本方案涉及甲基(3Z)-3-[(4-甲基[(4-甲基哌嗪-1-yl)乙酰]氨基}苯基)氨基](苯基)甲基亚甲基}-2-氧代-2,3-二氢-1H-吲哚-6-羧酸盐的晶体改性，其中HX代表至少一种酸组分，优选是甲磺酸，对甲苯磺酸，L-酒石酸，马来酸，乙酸和磷酸。另一方案还涉及其制备过程以及在药学可接受的组合物中使用它们的方法。本发明还涉及使用所述晶体形式的intedanib和制造的盐制备甲基(3Z)-3-[(4-甲基[(4-甲基哌嗪-1-yl)乙酰]氨基}苯基)氨基](苯基)甲基亚甲基}-2-氧代-2,3-二氢-1H-吲哚-6-羧酸的任何药学可接受盐的制备。
• Salts and crystalline salt forms of an 2-indolinone derivative
  申请人：Boehringer Ingelheim Pharma GmbH & Co. KG

  公开号：EP1870400A1

  公开（公告）日：2007-12-26

  The present invention relates to new salts and crystalline salt forms of an indolinone derivative which have valuable pharmacological properties, to a process for their manufacture, to pharmaceutical formulations containing them and to their use as medicament.

  本发明涉及一种具有重要药理特性的吲哚啉酮衍生物的新盐和结晶盐形式、其生产工艺、含有它们的药物制剂以及它们作为药物的用途。
• Saccharin salts and crystalline salt forms of an 2-indolinone derivative
  申请人：Boehringer Ingelheim Pharma GmbH & Co. KG

  公开号：EP2366689A1

  公开（公告）日：2011-09-21

  The present invention relates to saccharinate salts and crystalline salt forms of an indolinone derivative of the formula (I) which have valuable pharmacological properties, to a process for their manufacture, to pharmaceutical formulations containing them and to their use as medicament.

  本发明涉及式 (I) 的吲哚啉酮衍生物的糖盐和结晶盐形式 的糖盐和结晶盐形式，它们具有宝贵的药理特性，涉及其制造工艺、含有它们的药物制剂以及它们作为药物的用途。
• SALTS AND CRYSTALLINE SALT FORMS OF AN 2-INDOLINONE DERIVATIVE
  申请人：Boehringer Ingelheim International GmbH

  公开号：EP2029533A2

  公开（公告）日：2009-03-04
• New Salts and Crystalline Salt Forms of an Indolinone Derivative
  申请人：Sieger Peter

  公开号：US20090318471A1

  公开（公告）日：2009-12-24

  The present invention relates to new salts and crystalline salt forms of an indolinone derivative which have valuable pharmacological properties, to a process for their manufacture, to pharmaceutical formulations containing them and to their use as medicament.