(E)-3-(5-((5-chloro-2-oxoindolin-3-ylidene)methyl)furan-2-yl)benzoic acid | 1202918-24-8

• 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: (E)-3-(5-((5-chloro-2-oxoindolin-3-ylidene)methyl)furan-2-yl)benzoic acid
• 英文别名: 3-[5-[(E)-(5-chloro-2-oxo-1H-indol-3-ylidene)methyl]furan-2-yl]benzoic acid
• CAS: 1202918-24-8
• 化学式: C₂₀H₁₂ClNO₄
• 分子量: 365.773
• InChiKey: GSVOZLMGXZDHOR-MHWRWJLKSA-N

物化性质

• 沸点：
  656.7±55.0 °C(Predicted)
• 密度：
  1.454±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  79.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-3-(5-((5-chloro-2-oxoindolin-3-ylidene)methyl)furan-2-yl)benzoic acid 在 盐酸 、 N,N'-羰基二咪唑 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 49.0h， 生成 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 、 甲苯 为溶剂， 反应 4.0h， 生成 (E)-3-(5-((5-chloro-2-oxoindolin-3-ylidene)methyl)furan-2-yl)benzoic acid
  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。
• US8124649B2
  申请人：——

  公开号：US8124649B2

  公开（公告）日：2012-02-28
• [EN] OXINDOLE COMPOUNDS<br/>[FR] COMPOSÉS D'OXINDOLE
  申请人：CYLENE PHARMACEUTICALS INC

  公开号：WO2010002933A1

  公开（公告）日：2010-01-07

  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.
• Synthesis of [11C]CX-6258 as a new PET tracer for imaging of Pim kinases in cancer
  作者：Min Wang、Reynaldo Tzintzun、Mingzhang Gao、Zhidong Xu、Qi-Huang Zheng

  DOI：10.1016/j.bmcl.2015.07.061

  日期：2015.9

  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.
• Discovery of CX-6258. A Potent, Selective, and Orally Efficacious pan-Pim Kinases Inhibitor
  作者：Mustapha Haddach、Jerome Michaux、Michael K. Schwaebe、Fabrice Pierre、Sean E. O’Brien、Cosmin Borsan、Joe Tran、Nicholas Raffaele、Suchitra Ravula、Denis Drygin、Adam Siddiqui-Jain、Levan Darjania、Ryan Stansfield、Chris Proffitt、Diwata Macalino、Nicole Streiner、Joshua Bliesath、May Omori、Jeffrey P. Whitten、Kenna Anderes、William G. Rice、David M. Ryckman

  DOI：10.1021/ml200259q

  日期：2012.2.9

  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.