2-amino-N-(5-benzenesulfonyl-1H-indazol-3-yl)-4-(4-methyl-piperazin-1-yl)-benzamide | 1034974-45-2

• 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-amino-N-(5-benzenesulfonyl-1H-indazol-3-yl)-4-(4-methyl-piperazin-1-yl)-benzamide
• 英文别名: 2-amino-N-(5-benzenesulfonyl-1H-indazol-3-yl)-4-(4-methylpiperazin-1-yl)benzamide；2-amino-N-[5-(benzenesulfonyl)-1H-indazol-3-yl]-4-(4-methylpiperazin-1-yl)benzamide
• CAS: 1034974-45-2
• 化学式: C₂₅H₂₆N₆O₃S
• 分子量: 490.586
• InChiKey: JAIUSWPMZSECSF-UHFFFAOYSA-N

物化性质

• 沸点：
  734.6±60.0 °C(Predicted)
• 密度：
  1.409±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  133
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  四氢吡喃酮 、 2-amino-N-(5-benzenesulfonyl-1H-indazol-3-yl)-4-(4-methyl-piperazin-1-yl)-benzamide 在 三氟乙酸 、 tetramethylammonium triacetoxyborohydride 作用下， 以 二氯甲烷 为溶剂， 生成 N-(5-benzenesulfonyl-1H-indazol-3-yl)-4-(4-methyl-piperazin-1-yl)-2-(tetrahydro-pyran-4-ylamino)-benzamide
  参考文献：
  名称：

  WO2008/74749

  摘要：

  公开号：
• 作为产物：
  描述：

  N-(5-benzenesulfonyl-1H-indazol-3-yl)-4-(4-methyl-piperazin-1-yl)-2-nitro-benzamide 在 palladium 10% on activated carbon 作用下， 以 四氢呋喃 、 乙醇 、 水 、 环己烯 为溶剂， 反应 2.0h， 以86%的产率得到2-amino-N-(5-benzenesulfonyl-1H-indazol-3-yl)-4-(4-methyl-piperazin-1-yl)-benzamide
  参考文献：
  名称：

  WO2008/74749

  摘要：

  公开号：

文献信息

• Molecules for administration to ROS1 mutant cancer cells
  申请人：Ignyta, Inc.

  公开号：US10231965B2

  公开（公告）日：2019-03-19

  Substituted indazole derivatives of formula (I) or formula 2.(I) and pharmaceutically acceptable salts thereof, as defined in the specification, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful in therapy in the treatment of diseases associated with a deregulated protein kinase activity, like cancer.

  公开了公式（I）或公式2的取代吲唑衍生物以及其药用盐，如规范中所定义，其制备方法和包含它们的药物组合物；该发明的化合物可能在治疗与蛋白激酶活性失调相关的疾病，如癌症方面有用。
• [EN] PROCESS FOR THE PREPARATION OF SUBSTITUTED N-(5-BENZENESULFONYL-1H-INDAZOL-3-YL)-BENZAMIDES<br/>[FR] PROCÉDÉ POUR LA PRÉPARATION DE N-(5-BENZÈNESULFONYL-1H-INDAZOL-3-YL)-BENZAMIDES SUBSTITUÉS
  申请人：NERVIANO MEDICAL SCIENCES SRL

  公开号：WO2015110467A1

  公开（公告）日：2015-07-30

  The present invention relates to a process for the preparation of substituted N-(5-benzenesulfonyl-1 H-indazol-3-yl)-benzamides and to the useful intermediate compounds of such process. Such derivatives are described and claimed in WO2008/074749, which also discloses processes for their preparation. The process of the present invention allows to obtain the desired products in high yields and purity and with a limited number of steps. The synthesis starts from 5-iodo-1 H-indazol-3-ylamine and comprises, as the key steps, the coupling of an activated benzoic acid with a 5-phenylsulfanyl-1 H-indazol-3-ylamine scaffold and the subsequent oxidation of the sulfur atom, followed by further functional group transformations, which furnish the desired products. The compounds prepared according to the process of the present invention are endowed with protein kinase inhibiting activity and, more particularly, IGF-1R or ALK inhibiting activity. The compounds are therefore useful in the treatment of a variety of cancers, cell proliferative disorders and diseases associated with protein kinases.

  本发明涉及一种制备取代N-(5-苯磺酰基-1H-吲哚-3-基)-苯甲酰胺的过程，以及该过程中的有用中间化合物。这些衍生物在WO2008/074749中有描述和申请，该专利还公开了它们的制备方法。本发明的工艺允许以高收率和纯度，并且在有限步骤内获得所需产品。合成从5-碘-1H-吲哚-3-基胺开始，并包括关键步骤，即活化苯甲酸与5-苯基硫基-1H-吲哚-3-基胺支架的偶联，随后是硫原子的氧化，然后进行进一步的官能团转化，从而得到所需的产物。根据本发明的工艺制备的化合物具有蛋白激酶抑制活性，更具体地说是IGF-1R或ALK抑制活性。因此，这些化合物在治疗各种癌症、细胞增殖障碍和与蛋白激酶相关的疾病方面非常有用。
• INDAZOLE DERIVATIVES AS KINASE INHIBITORS FOR THE TREATMENT OF CANCER
  申请人：Bandiera Tiziano

  公开号：US20100197665A1

  公开（公告）日：2010-08-05

  Substituted indazole derivatives of formula (I) and pharmaceutically acceptable salts thereof, as defined in the specification, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful in therapy in the treatment of diseases associated with a dysregulated protein kinase activity, like cancer formula (I).

  本发明揭示了公式（I）的取代吲唑衍生物及其药学上可接受的盐，其定义在说明书中，以及其制备过程和包含它们的制药组合物；本发明的化合物可能在治疗与蛋白激酶活性失调相关的疾病，如癌症公式（I）中有用。
• Indazole derivatives as kinase inhibitors for the treatment of cancer
  申请人：Nerviano Medical Sciences S.R.L.

  公开号：US08114865B2

  公开（公告）日：2012-02-14

  Substituted indazole derivatives of formula (I) and pharmaceutically acceptable salts thereof, as defined in the specification, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful in therapy in the treatment of diseases associated with a dysregulated protein kinase activity, like cancer formula (I).

  本发明涉及公式(I)的取代吲唑衍生物及其药学上可接受的盐，其定义在规范中，以及制备它们的过程和包含它们的制药组合物；本发明的化合物可能在治疗与蛋白激酶活性失调相关的疾病中有用，例如癌症公式(I)。
• N-[5-(3,5-DIFLUOROBENZYL)-1H-INDAZOL-3-YL]-4-(4-METHYL-PIPERAZIN-1-YL)-2-(TETRAHYDRO-2H-PYRAN-4-YLAMINO) BENZAMIDE FOR TREATING PATIENTS WITH ROS1,NTRK1, NTRK2 AND NTRK3 MUTANT CANCER CELLS
  申请人：Ignyta, Inc.

  公开号：EP3834827A1

  公开（公告）日：2021-06-16

  Substituted indazole derivatives of formula (I) or formula 2.(I) and pharmaceutically acceptable salts thereof, as defined in the specification, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful in therapy in the treatment of diseases associated with a deregulated protein kinase activity, like cancer.

  本发明公开了式(I)或式2.(I)的取代吲唑衍生物及其药学上可接受的盐类（如说明书中所定义）、其制备工艺和包含它们的药物组合物；本发明的化合物可用于治疗与蛋白激酶活性失调有关的疾病（如癌症）。