(3E)-5-氯-3-[[5-[3-[(六氢-4-甲基-1H-14-二氮杂革-1-基)羰基]苯基]-2-呋喃]亚甲基]-1,3-二氢-2H-吲哚-2-酮 | 1202916-90-2

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 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
• 中文名称: (3E)-5-氯-3-[[5-[3-[(六氢-4-甲基-1H-14-二氮杂革-1-基)羰基]苯基]-2-呋喃]亚甲基]-1,3-二氢-2H-吲哚-2-酮
• 英文名称: CX-6258
• 英文别名: (E)-5-chloro-3-((5-(3-(4-methyl-1,4-diazepane-1-carbonyl)phenyl)furan-2-yl)methylene)indolin-2-one；(3E)-5-chloro-3-[[5-[3-(4-methyl-1,4-diazepane-1-carbonyl)phenyl]furan-2-yl]methylidene]-1H-indol-2-one
• CAS: 1202916-90-2
• 化学式: C₂₆H₂₄ClN₃O₃
• 分子量: 461.948
• InChiKey: KGBPLKOPSFDBOX-CJLVFECKSA-N

物化性质

• 沸点：
  697.8±55.0 °C(Predicted)
• 密度：
  1.309±0.06 g/cm3(Predicted)
• 溶解度：
  不溶于乙醇； DMSO 中≥11.15 mg/mL；温和加热时，水中≥2.575 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  33
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  65.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3E)-5-氯-3-[[5-[3-[(六氢-4-甲基-1H-14-二氮杂革-1-基)羰基]苯基]-2-呋喃]亚甲基]-1,3-二氢-2H-吲哚-2-酮 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 1.0h， 以48.71 g的产率得到化合物CX-6258HCL
  参考文献：
  名称：

  Discovery of CX-6258. A Potent, Selective, and Orally Efficacious pan-Pim Kinases Inhibitor

  摘要：

  Structure activity relationship analysis in a series of 3-(5-((2-oxoindolin-3-ylidene)methyl)furan-2-yl)amides identified compound 13, a pan-Pim kinases inhibitor with excellent biochemical potency and kinase selectivity. Compound 13 exhibited in vitro synergy with chemotherapeutics and robust in vivo efficacy in two Pim kinases driven tumor models.

  DOI：

  10.1021/ml200259q
• 作为产物：
  描述：

  5-溴-2-呋喃甲醛 在 哌啶 、 palladium diacetate 、 sodium carbonate 、 三苯基膦 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 28.0h， 生成 (3E)-5-氯-3-[[5-[3-[(六氢-4-甲基-1H-14-二氮杂革-1-基)羰基]苯基]-2-呋喃]亚甲基]-1,3-二氢-2H-吲哚-2-酮
  参考文献：
  名称：

  Synthesis of [11C]CX-6258 as a new PET tracer for imaging of Pim kinases in cancer

  摘要：

  The reference standard CX-6258 {(E)-5-chloro-3-((5-(3-(4-methyl-1,4-diazepane-1-carbonyl) phenyl) furan-2-yl) methylene) indolin-2-one, 4a} and its desmethylated precursor N-desmethyl-CX-6258 {(E)-3-((5-(3-(1,4-diazepane-1-carbonyl) phenyl) furan-2-yl) methylene)-5-chloroindolin-2-one, 5} for radiolabeling were synthesized from 5-bromo-2-furaldehyde and 3-carboxybenzeneboronic acid in 3 and 4 steps with 29-49% and 24-32% overall chemical yield, respectively. The target tracer [C-11] CX-6258 {(E)-5-chloro-3-((5-(3-(4-[11C] methyl-1,4-diazepane-1-carbonyl) phenyl) furan-2-yl) methylene) indolin-2-one, [C-11] 4a} was prepared from N-desmethyl-CX-6258 (5) with [C-11] CH3OTf under basic condition (2 N NaOH) through N-[C-11] methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 40-50% radiochemical yield based on [C-11] CO2 and decay corrected to end of bombardment (EOB) with 370-1110 GBq/mu mol specific activity at EOB. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.07.061

文献信息

• OXINDOLE COMPOUNDS
  申请人：HADDACH Mustapha

  公开号：US20100041635A1

  公开（公告）日：2010-02-18

  The invention provides compounds that inhibit PIM kinases and Flt3 kinase, and compositions containing such compounds. These compounds and compositions are useful for treating proliferative disorders such as cancer, as well as other kinase-associated conditions including inflammation.

  该发明提供了抑制PIM激酶和Flt3激酶的化合物，以及含有这些化合物的组合物。这些化合物和组合物对治疗癌症等增殖性疾病以及其他激酶相关疾病，如炎症，具有用处。
• PIM kinase inhibitors in combination with RNA splicing modulators/inhibitors for treatment of cancers
  申请人：UNIVERSITY OF MARYLAND, BALTIMORE COUNTY

  公开号：US10842785B2

  公开（公告）日：2020-11-24

  The present invention provides for a method of treating cancer and/or reducing proliferation of cancer cells, the method comprising administering to a subject in need of such treatment a composition comprising a PIM kinase inhibitor that exhibits changes of mRNA splicing in combination with a compound that modulates/inhibits activity of an RNA splicing factor protein. Further, changes in splicing of mRNAs and phosphorylation of RNA splicing factors can be used as biomarkers for patient responsiveness to anti-PIM treatment and also suggest effective combinatorial therapies, including synergistic combination.

  本发明提供了一种治疗癌症和/或减少癌细胞增殖的方法，该方法包括向需要这种治疗的受试者施用一种组合物，该组合物包含一种PIM激酶抑制剂，该PIM激酶抑制剂与一种调节/抑制RNA剪接因子蛋白活性的化合物相结合，可显示出mRNA剪接的变化。此外，mRNA 的剪接变化和 RNA 剪接因子的磷酸化可用作患者对抗 PIM 治疗反应性的生物标志物，还可提示有效的组合疗法，包括协同组合疗法。
• Compositions and methods for the treatment of aberrant angiogenesis
  申请人：The Schepens Eye Research Institute, Inc.

  公开号：US11229662B2

  公开（公告）日：2022-01-25

  The present subject matter provides compositions, formulations, and methods for inhibiting, treating, or preventing aberrant angiogenesis in a subject.

  本主题提供了用于抑制、治疗或预防受试者异常血管生成的组合物、制剂和方法。
• PIM kinase inhibitors in combination with autophagy inhibitors for treatment of cancers
  申请人：UNIVERSITY OF MARYLAND, BALTIMORE COUNTY

  公开号：US11389440B2

  公开（公告）日：2022-07-19

  The present invention provides for a method of treating cancer and/or reducing proliferation of cancer cells, the method comprising administering to a subject in need of such treatment a composition comprising a PIM kinase inhibitor that exhibits changes in expressed RNA or ribosomal binding proteins in combination with a compound that inhibits autophagy.

  本发明提供了一种治疗癌症和/或减少癌细胞增殖的方法，该方法包括向需要这种治疗的受试者施用一种组合物，该组合物包含一种 PIM 激酶抑制剂，该抑制剂与一种抑制自噬的化合物结合使用，后者在表达的 RNA 或核糖体结合蛋白中显示出变化。
• PIM KINASE INHIBITORS IN COMBINATION WITH RNA SPLICING MODULATORS/INHIBITORS FOR TREATMENT OF CANCERS
  申请人：University of Maryland, Baltimore County

  公开号：EP3432886B1

  公开（公告）日：2021-06-02