3-chloro-4-(5-fluoro-1H-indol-3-yl)-1-methyl-1H-pyrrole-2,5-dione | 1133458-18-0

• 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-chloro-4-(5-fluoro-1H-indol-3-yl)-1-methyl-1H-pyrrole-2,5-dione
• 英文别名: 3-chloro-4-(5-fluoro-1H-indol-3-yl)-1-methylpyrrole-2,5-dione
• CAS: 1133458-18-0
• 化学式: C₁₃H₈ClFN₂O₂
• 分子量: 278.67
• InChiKey: OEGOEDBSCVTVRW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  53.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-chloro-4-(5-fluoro-1H-indol-3-yl)-1-methyl-1H-pyrrole-2,5-dione 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 3-(4-chloro-1-methyl-2,5-dihydro-1H-pyrrol-3-yl)-5-fluoro-1H-indole
  参考文献：
  名称：

  Rigidized 1-aryl sulfonyl tryptamines: Synthesis and pharmacological evaluation as 5-HT6 receptor ligands

  摘要：

  A series of N-1-arylsulfonyl-3-(pyrrolidin-3-yl)-1H-indole and N-1-arylsulfonyl-3-(4-chloro-2,5-dihydro-1H-pyrrol-3-yl)-1H-indole derivatives (tryptamine derivatives with rigidized side chain) have been prepared and tested for their binding affinity to 5-HT6 receptor. Several compounds displayed potent binding affinity for the 5-HT6 receptor when tested in in vitro binding assay. The primary SAR indicates that rigidification of dimethylamino alkyl chain at C-3 of indole carbon maintains the binding affinity to 5-HT6R. The lead compound N-1-benzenesulfonyl-3-(4-chloro-1-methyl-2,5-dihydro-1H-pyrrol-3-yl)-1H-indole, 10a (K-b = 0.1 nM) has shown excellent in vitro affinity and was active in animal models of cognition like NORT and water maze. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.106
• 作为产物：
  描述：

  2,3-二氯马来酸酐 、 5-氟-1H-茚 在 乙基溴化镁 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 2.75h， 以89%的产率得到3-chloro-4-(5-fluoro-1H-indol-3-yl)-1-methyl-1H-pyrrole-2,5-dione
  参考文献：
  名称：

  通过C 2对称双氮丙啶的亲核开合合成星形孢菌素，K-252a和瑞贝卡霉素的新氮杂类似物†

  摘要：

  稳定的， 水-易溶 氨基糖 星形孢菌素， K-252a已经通过双吲哚基马来酰亚胺对C 2对称的N-活化的N-活化的双氮丙啶进行亲核打开，制备了瑞贝卡霉素和瑞贝卡霉素类似物。这种不同的策略允许合成不对称取代的衍生物，并提供了一种容易的方法哌啶 和 吡咯烷 类似物。

  DOI：

  10.1039/b815737e

文献信息

• Rigidized 1-aryl sulfonyl tryptamines: Synthesis and pharmacological evaluation as 5-HT6 receptor ligands
  作者：Ramakrishna Nirogi、Adireddy Dwarampudi、Ramasastry Kambhampati、Venugopalarao Bhatta、Laxman Kota、Anil Shinde、Rajesh Badange、Pradeep Jayarajan、Gopinadh Bhyrapuneni、P.K. Dubey

  DOI：10.1016/j.bmcl.2011.05.106

  日期：2011.8

  A series of N-1-arylsulfonyl-3-(pyrrolidin-3-yl)-1H-indole and N-1-arylsulfonyl-3-(4-chloro-2,5-dihydro-1H-pyrrol-3-yl)-1H-indole derivatives (tryptamine derivatives with rigidized side chain) have been prepared and tested for their binding affinity to 5-HT6 receptor. Several compounds displayed potent binding affinity for the 5-HT6 receptor when tested in in vitro binding assay. The primary SAR indicates that rigidification of dimethylamino alkyl chain at C-3 of indole carbon maintains the binding affinity to 5-HT6R. The lead compound N-1-benzenesulfonyl-3-(4-chloro-1-methyl-2,5-dihydro-1H-pyrrol-3-yl)-1H-indole, 10a (K-b = 0.1 nM) has shown excellent in vitro affinity and was active in animal models of cognition like NORT and water maze. (C) 2011 Elsevier Ltd. All rights reserved.
• Synthesis of new aza-analogs of staurosporine, K-252a and rebeccamycin by nucleophilic opening of C₂-symmetric bis-aziridines
  作者：Sandrine Delarue-Cochin、Isabelle McCort-Tranchepain

  DOI：10.1039/b815737e

  日期：——

  Stable, water-soluble aminosugar staurosporine, K-252a and rebeccamycin analogs have been prepared by nucleophilic opening of C2-symmetric N-activated bis-aziridines by bis-indolylmaleimides. This divergent strategy allows the synthesis of unsymmetrical substituted derivatives and provides an easy access to the piperidine and pyrrolidine analogs.

  稳定的， 水-易溶 氨基糖 星形孢菌素， K-252a已经通过双吲哚基马来酰亚胺对C 2对称的N-活化的N-活化的双氮丙啶进行亲核打开，制备了瑞贝卡霉素和瑞贝卡霉素类似物。这种不同的策略允许合成不对称取代的衍生物，并提供了一种容易的方法哌啶 和 吡咯烷 类似物。