2-methyl-7-[1,2-dihydro-5-fluoro-2-oxo-3H-indol-(Z)-3-ylidene]-4,5,6,7-tetrahydro-1H-indole-3-carboxylic acid | 1032267-99-4

• 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: 2-methyl-7-[1,2-dihydro-5-fluoro-2-oxo-3H-indol-(Z)-3-ylidene]-4,5,6,7-tetrahydro-1H-indole-3-carboxylic acid
• 英文别名: (7Z)-7-(5-fluoro-2-oxo-1H-indol-3-ylidene)-2-methyl-1,4,5,6-tetrahydroindole-3-carboxylic acid
• CAS: 1032267-99-4
• 化学式: C₁₈H₁₅FN₂O₃
• 分子量: 326.327
• InChiKey: UCSBDEBAWBNTRX-PTNGSMBKSA-N

物化性质

• 沸点：
  635.2±55.0 °C(Predicted)
• 密度：
  1.472±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  82.2
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N,N-二乙基乙二胺 、 2-methyl-7-[1,2-dihydro-5-fluoro-2-oxo-3H-indol-(Z)-3-ylidene]-4,5,6,7-tetrahydro-1H-indole-3-carboxylic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 苹果酸他菲替尼
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of novel 3-pyrrolo[b]cyclohexylene-2-dihydroindolinone derivatives as potent receptor tyrosine kinase inhibitors

  摘要：

  A novel series of 3-pyrrolo[b]cyclohexylene-2-dihydroindolinone derivatives targeting VEGFR-2, PDGFR-beta and c-Kit kinases were designed and synthesized. The molecular design was based on the SAR features of indolin-2-ones as kinase inhibitors. SAR study of the series allowed us to identify compounds possessing more potent inhibitory activities against the three kinases than sunitinb with IC50 values in the low nanomolar range in vitro. Additionally, some compounds also showed favorable antiproliferative activities against a panel of cancer cell lines (BXPC-3, T24, BGC, HEPG2 and HT29). (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.08.037
• 作为产物：
  描述：

  6-amino-5-oxohexanoic acid hydrochloride 在 吡啶 、 sodium dihydrogenphosphate 、 四磷十氧化物 、 四氯化钛 、 lithium hydroxide 作用下， 以 水 为溶剂， 反应 84.5h， 生成 2-methyl-7-[1,2-dihydro-5-fluoro-2-oxo-3H-indol-(Z)-3-ylidene]-4,5,6,7-tetrahydro-1H-indole-3-carboxylic acid
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of novel 3-pyrrolo[b]cyclohexylene-2-dihydroindolinone derivatives as potent receptor tyrosine kinase inhibitors

  摘要：

  A novel series of 3-pyrrolo[b]cyclohexylene-2-dihydroindolinone derivatives targeting VEGFR-2, PDGFR-beta and c-Kit kinases were designed and synthesized. The molecular design was based on the SAR features of indolin-2-ones as kinase inhibitors. SAR study of the series allowed us to identify compounds possessing more potent inhibitory activities against the three kinases than sunitinb with IC50 values in the low nanomolar range in vitro. Additionally, some compounds also showed favorable antiproliferative activities against a panel of cancer cell lines (BXPC-3, T24, BGC, HEPG2 and HT29). (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.08.037

文献信息

• 3-Pyrrolo[b]Cyclohexylene-2-Dihydroindolinone Derivatives and Uses Thereof
  申请人：Tang Feng

  公开号：US20100160318A1

  公开（公告）日：2010-06-24

  3-pyrrolo[b]cyclohexylene-2-dihydro-indolinone derivatives of formula (I) or their pharmaceutically acceptable salts and uses thereof. The intermediates of formula (II) for preparing the above compounds. The bioassay shows that the above compounds and their pharmaceutically acceptable salts can modulate the activity of protein kinases (PKs), inhibit the activity of tyrosine kinases (PTKs) and inhibit many kinds of tumor cells as well as.

  公式（I）的3-吡咯[ b ]环己烯-2-二氢吲哚酮衍生物或其药用盐及其用途。用于制备上述化合物的公式（II）的中间体。生物测定表明，上述化合物及其药用盐可以调节蛋白激酶（PKs）的活性，抑制酪氨酸激酶（PTKs）的活性，并抑制多种类型的肿瘤细胞。
• Bioorga. Med. Chem. Lett. 2013, 23, 5630-5633
  作者：

  DOI：——

  日期：——
• NOVEL PHARMACEUTICAL FORMULATIONS CONTAINING INDIRUBIN AND DERIVATIVES THEREOF AND METHODS OF MAKING AND USING THE SAME
  申请人：Phosphorex, Inc.

  公开号：EP3600259A1

  公开（公告）日：2020-02-05
• US8084621B2
  申请人：——

  公开号：US8084621B2

  公开（公告）日：2011-12-27
• [EN] NOVEL PHARMACEUTICAL FORMULATIONS CONTAINING INDIRUBIN AND DERIVATIVES THEREOF AND METHODS OF MAKING AND USING THE SAME<br/>[FR] NOUVELLES FORMULATIONS PHARMACEUTIQUES CONTENANT DE L'INDIRUBINE ET DES DÉRIVÉS DE CELUI-CI ET PROCÉDÉS DE FABRICATION ET D'UTILISATION DE CELLES-CI
  申请人：PHOSPHOREX INC

  公开号：WO2018183631A1

  公开（公告）日：2018-10-04

  The invention described herein provides various indirubin compositions for treating diseases.