3,3-dibromo-2-oxo-2,3-dihydro-1H-indole-5-carboxylic acid methyl ester | 953029-80-6

• 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: 3,3-dibromo-2-oxo-2,3-dihydro-1H-indole-5-carboxylic acid methyl ester
• 英文别名: methyl 3,3-dibromo-2-oxo-1H-indole-5-carboxylate
• CAS: 953029-80-6
• 化学式: C₁₀H₇Br₂NO₃
• 分子量: 348.978
• InChiKey: OMYNSZMYTHDIPA-UHFFFAOYSA-N

物化性质

• 熔点：
  >300 °C(Solv: acetone (67-64-1))
• 沸点：
  436.0±45.0 °C(Predicted)
• 密度：
  1.981±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3,3-dibromo-2-oxo-2,3-dihydro-1H-indole-5-carboxylic acid methyl ester 在 盐酸 作用下， 以 水 为溶剂， 反应 0.08h， 生成 2,3-二氧代吲哚啉-5-甲酸
  参考文献：
  名称：

  Inhibitors of Src Homology-2 Domain Containing Protein Tyrosine Phosphatase-2 (Shp2) Based on Oxindole Scaffolds

  摘要：

  Screening of the NCl diversity set of compounds has led to the identification of 5 (NSC-117199), which inhibits the protein tyrosine phosphatase (PTP) Shp2 with an IC(50) of 47 mu M. A focused library incorporating an isatin scaffold was designed and evaluated for inhibition of Shp2 and Shp1 PTP activities. Several compounds were identified that selectively inhibit Shp2 over ShpI and PTP1B with low to submicromolar activity. A model for the binding of the active compounds is proposed.

  DOI：

  10.1021/jm8002526
• 作为产物：
  描述：

  吲哚-5-甲酸甲酯 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 异丙醇 为溶剂， 反应 0.75h， 以55%的产率得到3,3-dibromo-2-oxo-2,3-dihydro-1H-indole-5-carboxylic acid methyl ester
  参考文献：
  名称：

  WO2007/117699

  摘要：

  公开号：

文献信息

• Inhibition of Shp2/PTPN11 Protein Tyrosine Phosphatase by NSC-87877, NSC-117199 and Their Analogs
  申请人：Wu Jie

  公开号：US20080176309A1

  公开（公告）日：2008-07-24

  Compounds and associated methods for inhibiting a protein tyrosine phosphatase. By a combination of experimental and virtual screenings of the NCI Diversity Set chemical library, NSC-87877 and NSC-117199 have been identified as Shp2 PTP inhibitors. Significantly, NSC-87877 is active in cell-based assays and has no detectable off-target effects in the EGF-stimulated Erk1/2 activation pathway. Additionally, a number of analogs of NSC-117199 have been produced. These analogs exhibit enhanced protein tyrosine phosphatase inhibition and are found to be potent and/or selective inhibitors of Shp1 and/or Shp2 protein tyrosine phosphatases.

  化合物及其相关方法，用于抑制蛋白酪氨酸磷酸酶。通过NCI Diversity Set化学库的实验和虚拟筛选的组合，已经确定NSC-87877和NSC-117199是Shp2 PTP抑制剂。值得注意的是，NSC-87877在基于细胞的实验中是活性的，并且在EGF刺激的Erk1/2激活途径中没有检测到任何非靶效应。此外，已经生产了许多NSC-117199的类似物。这些类似物表现出增强的蛋白酪氨酸磷酸酶抑制作用，并被发现是Shp1和/或Shp2蛋白酪氨酸磷酸酶的有效和/或选择性抑制剂。
• WO2007/117699
  申请人：——

  公开号：——

  公开（公告）日：——
• US8987474B2
  申请人：——

  公开号：US8987474B2

  公开（公告）日：2015-03-24
• [EN] INHIBITION OF SHP2/PTPN11 PROTEIN TYROSINE PHOSPHATASE BY NSC-87877, NSC-117199 AND THEIR ANALOGS<br/>[FR] INHIBITION DE LA PROTEINE TYROSINE PHOSPHATASE SHP2/PTPN11 PAR NSC-87877, NSC-117199 ET LEURS ANALOGUES
  申请人：UNIV SOUTH FLORIDA

  公开号：WO2007117699A2

  公开（公告）日：2007-10-18

  [EN] Compounds and associated methods for inhibiting a protein tyrosine phosphatase. By a combination of experimental and virtual screenings of the NCI Diversity Set chemical library, NSC-87877 and NSC-117199 have been identified as Shp2 PTP inhibitors. Significantly, NSC-87877 is active in cell-based assays and has no detectable off-target effects in the EGF-stimulated Erkl/2 activation pathway. Additionally, a number of analogs of NSC-1 17199 have been produced. These analogs exhibit enhanced protein tyrosine phosphatase inhibition and arc found to be potent and/or selectiv e inhibitors of Shp l and/or Shp2 protein tyrosine phosphatases.
  [FR] La présente invention concerne des composés et des procédés associés permettant d'inhiber une protéine tyrosine phosphatase. Grâce à une association de criblages expérimentaux et virtuels de la banque chimique Diversity Set du NCI, on a pu identifier le NSC-87877 et le NSC-117199 comme inhibiteurs du Shp2 PTP. De manière significative, le NSC-87877 est actif dans des analyses cellulaires et ne présente aucun effet non ciblé détectable dans la voie d'activation Erkl/2 stimulée par EGF. En outre, un certain nombre d'analogues du NSC-1 17199 ont été produits. Ces analogues présentent une inhibition accrue de la protéine tyrosine phosphatase et sont des inhibiteurs puissants et/ou sélectifs des protéines tyrosines phosphatases Shpl et/ou Shp2.
• [EN] INHIBITION OF SHP2/PTPN11 PROTEIN TYROSINE PHOSPHATASE BY NSC-117199 AND ANALOGS<br/>[FR] INHIBITION DE LA PROTÉINE TYROSINE PHOSPHATASE SHP2/PTPN11 PAR NSC-117199 ET ANALOGUES
  申请人：H LEE MOFFITT CANCER CT AND RE

  公开号：WO2009135000A2

  公开（公告）日：2009-11-05

  Protein tyrosine phosphatase (PTP) Shp2 is a non-receptor PTP that involved in cell signaling and regulation of cell proliferation, differentiation, and migration. Shp2 mediates activation of kinases that are involved in the pathogenesis of human carcinoma. NSC-117199 was identified as a porent inhibitor of the protein tyrosine phosphatase (PTPa) Shp2. A focused library of analogs incorporating an isatin scaffold was designed and evaluated for inhibition of Shp2 and Shp1 PTP activities. Several compounds were identified that selectively inhibit Shp2 over Shp1 and PTP1B with low to sub-micromolar activity. Also disclosed are methods of inhibiting a protein tyrosine phosphatase in a cell and treating cancer through selective inhibition of Shp2.