N-{5-[5-fluoro-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrol-3-yl}-3-(4-ethylpiperazin-1-yl)propionamide | 1351529-95-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-{5-[5-fluoro-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrol-3-yl}-3-(4-ethylpiperazin-1-yl)propionamide
• 英文别名: 3-(4-ethylpiperazin-1-yl)-N-[5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrol-3-yl]propanamide
• CAS: 1351529-95-7
• 化学式: C₂₄H₃₀FN₅O₂
• 分子量: 439.533
• InChiKey: UCVSBXVAWNHNTF-RGEXLXHISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.23
• 重原子数：
  32.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  80.47
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  3,5-二甲基-2-吡咯甲醛 在 四氢吡咯 、 硫酸 、 溶剂黄146 、 potassium nitrate 、 4-(4,6-二甲氧基三嗪-2-基)-4-甲基吗啉盐酸盐 、 锌 作用下， 以 乙醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 N-{5-[5-fluoro-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrol-3-yl}-3-(4-ethylpiperazin-1-yl)propionamide
  参考文献：
  名称：

  PYRROLYL SUBSTITUTED DIHYDROINDOL-2-ONE DERIVATIVES, PREPARATION METHODS AND USES THEREOF

  摘要：

  提供了由式（I）表示的吡咯基取代的二氢吲哚-2-酮衍生物，以及该衍生物的药用可接受的盐或溶剂，或该盐的溶剂，这些衍生物是有效的酪氨酸激酶抑制剂。还提供了上述化合物的制备方法，含有这些化合物的药物组合物，以及利用这些化合物制造对治疗或辅助治疗由酪氨酸激酶介导的肿瘤或哺乳动物（包括人类）中由酪氨酸激酶驱动的肿瘤细胞增殖或迁移有用的药物。

  公开号：

  US20130158030A1

文献信息

• Pyrrolyl substituted dihydroindol-2-one derivatives, preparation methods and uses thereof
  申请人：Wang Jingyi

  公开号：US08637681B2

  公开（公告）日：2014-01-28

  Provided are pyrrolyl substituted dihydroindol-2-one derivatives represented by formula (I), pharmaceutically acceptable salts or solvates of said derivatives, or solvates of said salts, which are effective tyrosine kinase inhibitors. Also provided are the preparation methods of the above compounds, pharmaceutical compositions containing these compounds, and the use of these compounds in manufacturing drugs useful for the treatment or adjunctive treatment of tumors medicated by tyrosine kinases or proliferation or migration of tumor cells driven by tyrosine kinases in mammals (including human).

  提供的是公式（I）所代表的吡咯基取代的二氢吲哚-2-酮衍生物、该衍生物的药学上可接受的盐或溶剂合物，或该盐的溶剂合物，其是有效的酪氨酸激酶抑制剂。还提供了上述化合物的制备方法，含有这些化合物的制药组合物，以及使用这些化合物制造用于治疗或辅助治疗哺乳动物（包括人类）中由酪氨酸激酶介导的肿瘤或由酪氨酸激酶驱动的肿瘤细胞增殖或迁移的药物的用途。
• Synthesis and in vivo SAR study of indolin-2-one-based multi-targeted inhibitors as potential anticancer agents
  作者：Long Zhang、Qingmei Zheng、Yingying Yang、Haojie Zhou、Xingjiang Gong、Shuyong Zhao、Chuanwen Fan

  DOI：10.1016/j.ejmech.2014.05.051

  日期：2014.7

  A series of indolin-2-one analogues were designed and synthesized, and all of them exhibited excellent in vitro potency. The structure and in vivo activity or toxicity relationship (in-vivo SAR) investigation of indolin-2-one structural analogues was carried out. In vivo efficacy studies indicated that 3b significantly suppressed tumor growth in HT-29 and NCI-H460 xenografts without causing significant loss of body weight. Kinase assay showed that compound 3b effectively inhibited the VEGFR-2, VEGFR-3, FLT3, Ret and PDGFR-beta kinases, but had little effect on the VEGFR-1 kinase. Besides, 3b showed higher selectivity for VEGFR-2 compared with PDGFR-beta. On the basis of its selectivity and safety properties, 3b was identified as a drug candidate for the treatment of cancer. (C) 2014 Elsevier Masson SAS. All rights reserved.
• US8637681B2
  申请人：——

  公开号：US8637681B2

  公开（公告）日：2014-01-28