[5-amino-1-(2-methyl-1H-benzimidazol-5-yl)-1H-pyrazol-4-yl](6-morpholin-4-ylmethyl-1H-indol-2-yl)methanone | 1265230-56-5

• 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: [5-amino-1-(2-methyl-1H-benzimidazol-5-yl)-1H-pyrazol-4-yl](6-morpholin-4-ylmethyl-1H-indol-2-yl)methanone
• 英文别名: [5-amino-1-(2-methyl-1H-benzimidazol-5-yl)-1H-pyrazol-4-yl]-(6-morpholin-4-ylmethyl-1H-indol-2-yl)-methanone；[5-amino-1-(2-methyl-3H-benzimidazol-5-yl)pyrazol-4-yl]-[6-(morpholin-4-ylmethyl)-1H-indol-2-yl]methanone
• CAS: 1265230-56-5
• 化学式: C₂₅H₂₅N₇O₂
• 分子量: 455.519
• InChiKey: TVWOUPGUUIDZET-UHFFFAOYSA-N

物化性质

• 沸点：
  817.3±65.0 °C(Predicted)
• 密度：
  1.50±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  118
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  [5-amino-1-(2-methyl-1H-benzimidazol-5-yl)-1H-pyrazol-4-yl]-(1-benzenesulfonyl-6-morpholin-4-ylmethyl-1H-indol-2-yl)-methanone 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 22.0h， 以75%的产率得到[5-amino-1-(2-methyl-1H-benzimidazol-5-yl)-1H-pyrazol-4-yl](6-morpholin-4-ylmethyl-1H-indol-2-yl)methanone
  参考文献：
  名称：

  AMINOPYRAZOLE DERIVATIVE

  摘要：

  公开号：

  EP2471786B1

文献信息

• Discovery of [5-Amino-1-(2-methyl-3<i>H</i>-benzimidazol-5-yl)pyrazol-4-yl]-(1<i>H</i>-indol-2-yl)methanone (CH5183284/Debio 1347), An Orally Available and Selective Fibroblast Growth Factor Receptor (FGFR) Inhibitor
  作者：Hirosato Ebiike、Naoki Taka、Masayuki Matsushita、Masayuki Ohmori、Kyoko Takami、Ikumi Hyohdoh、Masami Kohchi、Tadakatsu Hayase、Hiroki Nishii、Kenji Morikami、Yoshito Nakanishi、Nukinori Akiyama、Hidetoshi Shindoh、Nobuya Ishii、Takehito Isobe、Hiroharu Matsuoka

  DOI：10.1021/acs.jmedchem.6b01156

  日期：2016.12.8

  The fibroblast growth factor receptor (FGFR) family of receptor tyrosine kinases regulates multiple biological processes, such as cell proliferation, migration, apoptosis, and differentiation. Various genetic alterations that drive activation of the receptors and the pathway are associated with tumor growth and survival; therefore, the FGFR family represents an attractive therapeutic target for treating

  受体酪氨酸激酶的成纤维细胞生长因子受体（FGFR）家族调节多种生物学过程，例如细胞增殖，迁移，凋亡和分化。驱动受体和途径活化的各种遗传改变与肿瘤的生长和存活有关。因此，FGFR家族代表了用于治疗癌症的有吸引力的治疗靶标。在这里，我们报告8（CH5183284 / Debio 1347），一种FGFR1，FGFR2和FGFR3的口服可用和选择性抑制剂的发现和药理作用。由抑制剂和FGFR的3D模型分析指导的化学修饰导致鉴定出对FGFR1，FGFR2和FGFR3具有选择性的抑制剂。在小鼠的体外研究和异种移植模型中，8显示出对具有遗传改变的FGFR的癌细胞系的抗肿瘤活性。这些结果支持了8作为一种新的抗癌药的潜在治疗用途。
• Aminopyrazole Derivative
  申请人：Taka Naoki

  公开号：US20120208811A1

  公开（公告）日：2012-08-16

  A compound represented by formula (I) or a pharmacologically acceptable salt thereof, which can inhibit a fibroblast growth factor receptor (FGFR) family kinase in cancer tissues. (In the formula, A represents a 5- to 10-membered heteroaryl group, or a C 6-10 aryl group; R 1 and R 2 independently represent H, OH, X, CN, NO 2 , a C 1-4 haloalkyl group, a C 1-6 alkyl group, or the like ; R 3 represents H, a C 1-5 alkyl group, a C 6-10 aryl group, a C 1-5 alkyl group, or a C 1-4 haloalkyl group; and R 4 represents H, X, a C 1-3 alkyl group, a C 1-4 haloalkyl group, OH, CN, NO 2 , or the like.)

  化合物(I)或其药学上可接受的盐，可以抑制癌组织中的成纤维细胞生长因子受体（FGFR）家族激酶。在公式中，A代表5-至10-成员的杂环芳基基团或C6-10芳基基团；R1和R2独立地表示H、OH、X、CN、NO2、C1-4卤代烷基、C1-6烷基或类似物；R3表示H、C1-5烷基、C6-10芳基基团、C1-5烷基或C1-4卤代烷基；R4表示H、X、C1-3烷基、C1-4卤代烷基、OH、CN、 或类似物。
• Aminopyrazole derivative
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：US09102692B2

  公开（公告）日：2015-08-11

  A method for treating cancer that includes administering a pharmaceutically effective amount of a composition containing a compound represented by formula (I) or a pharmacologically acceptable salt thereof. In the formula, A represents a 5- to 10-membered heteroaryl group, or a C6-10 aryl group; R1 and R2 independently represent H, OH, X, CN, NO2, a C1-4 haloalkyl group, a C1-6 alkyl group, or the like ; R3 represents H, a C1-5 alkyl group, a C6-10 aryl group, a C1-5 alkyl group, or a C1-4 haloalkyl group; and R4 represents H, X, a C1-3 alkyl group, a C1-4 haloalkyl group, OH, CN, NO2, or the like.

  一种治疗癌症的方法，包括给予含有式（I）所表示的化合物或其药理学上可接受的盐的药物有效量的组合物。在该式中，A表示一个5-至10-成员的杂环芳基基团或一个C6-10芳基基团；R1和R2独立地表示H、OH、X、CN、NO2、C1-4卤代烷基、C1-6烷基或类似物；R3表示H、C1-5烷基、C6-10芳基基团、C1-5烷基或C1-4卤代烷基；R4表示H、X、C1-3烷基、C1-4卤代烷基、OH、CN、 或类似物。
• FGFR gatekeeper mutant gene and drug targeting same
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：US10391081B2

  公开（公告）日：2019-08-27

  The present inventors successfully identified novel gatekeeper mutations for FGFR. Further, they discovered that mutant FGFR having the mutations demonstrate resistance to known FGFR inhibitors such as AZD4547, and at the same time demonstrate sensitivity to specific compounds. Mutant polypeptides having the mutations may be used as biomarkers in cancer treatment by FGFR inhibitors to prevent the development of side effects in therapy by conventional FGFR inhibitors, and to control the therapeutic mode for receiving the best therapeutic effect, thus making individualized treatment possible.

  本发明者成功鉴定了新型的 FGFR 守门突变。此外，他们还发现，具有这些突变的突变型 FGFR 对已知的 FGFR 抑制剂（如 AZD4547）表现出抗性，同时对特定化合物表现出敏感性。具有这些突变的突变多肽可用作 FGFR 抑制剂治疗癌症的生物标志物，以防止传统 FGFR 抑制剂在治疗过程中产生副作用，并控制治疗模式以获得最佳治疗效果，从而使个体化治疗成为可能。
• FGFR3 fusion gene and pharmaceutical drug targeting same
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：US10689705B2

  公开（公告）日：2020-06-23

  The FGFR-encoding gene was studied extensively with regard to its expression, hyperamplification, mutation, translocation, or such in various cancer cells. As a result, novel fusion polypeptides in which the FGFR3 polypeptide is fused with a different polypeptide were identified and isolated from several types of bladder cancer-derived cells and lung cancer cells. The use of a fusion polypeptide of the present invention as a biomarker in FGFR inhibitor-based cancer therapy enables one to avoid side effects in cancer therapy and control the therapeutic condition to produce the best therapeutic effect, thereby enabling individualized medicine.

  对表皮生长因子受体编码基因在各种癌细胞中的表达、高扩增、突变、易位等情况进行了广泛研究。结果，从几种类型的膀胱癌衍生细胞和肺癌细胞中鉴定并分离出了新型融合多肽，其中 FGFR3 多肽与另一种多肽融合。在基于表皮生长因子受体抑制剂的癌症治疗中，使用本发明的融合多肽作为生物标记物，可以避免癌症治疗中的副作用，控制治疗条件以产生最佳治疗效果，从而实现个体化医疗。