1-(2-bromobenzenesulfonyl)-3-(1-methylpyrrolidin-3-yl)-5-methoxy-1H-indole | 859832-44-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(2-bromobenzenesulfonyl)-3-(1-methylpyrrolidin-3-yl)-5-methoxy-1H-indole
• 英文别名: (R,S)-1-(2-bromobenzenesulfonyl)-3-(1-methylpyrrolidin-3-yl)-5-methoxy-1H-indole；1-(2-Bromophenyl)sulfonyl-5-methoxy-3-(1-methylpyrrolidin-3-yl)indole
• CAS: 859832-44-3
• 化学式: C₂₀H₂₁BrN₂O₃S
• 分子量: 449.368
• InChiKey: DRHAGPVCFUFBDL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  59.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(2-bromobenzenesulfonyl)-3-(1-methylpyrrolidin-3-yl)-5-methoxy-1H-indole 在 四(三苯基膦)钯 、 potassium acetate 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 5.0h， 生成 (R,S) 2-methoxy-10-(1-methylpyrrolidin-3-yl)-5-thia-4b-aza-indeno[2,1-a]indene 5,5-dioxide
  参考文献：
  名称：

  Synthesis and Structure Activity Relationship of Rigidized Indolyl Pyrrolidine Derivatives as 5-HT6 Receptor Ligands

  摘要：

  一系列新型刚性吲哚基吡咯烷衍生物通过限制色氨酸胺氮原子与a和b碳的结合而设计。所有合成的衍生物在体外结合测定中对5-HT6R表现出中等亲和力。本通讯的主题是选定化合物的合成、结构活性关系（SAR）、药代动力学特征以及体内疗效。

  DOI：

  10.14233/ajchem.2013.15443
• 作为产物：
  描述：

  5-甲氧基吲哚 在 lithium aluminium tetrahydride 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 1-(2-bromobenzenesulfonyl)-3-(1-methylpyrrolidin-3-yl)-5-methoxy-1H-indole
  参考文献：
  名称：

  Synthesis and Structure Activity Relationship of Rigidized Indolyl Pyrrolidine Derivatives as 5-HT6 Receptor Ligands

  摘要：

  一系列新型刚性吲哚基吡咯烷衍生物通过限制色氨酸胺氮原子与a和b碳的结合而设计。所有合成的衍生物在体外结合测定中对5-HT6R表现出中等亲和力。本通讯的主题是选定化合物的合成、结构活性关系（SAR）、药代动力学特征以及体内疗效。

  DOI：

  10.14233/ajchem.2013.15443

文献信息

• [EN] 3-(PYROLIDIN-3-L) INDOLES AS 5-HT6 RECEPTOR MODULATORS<br/>[FR] 3-(PYRROLIDINE-3-L)INDOLES EN TANT QUE MODULATEURS DU RECEPTEUR 5-HT6
  申请人：SUVEN LIFE SCIENCES

  公开号：WO2005066157A1

  公开（公告）日：2005-07-21

  The present invention describes 3-(Heterocyclic)indoles with the Formula (I), its stereoisomers and salts, wherein the substituents such as R, R1, R2, R3, R4, R10, R11, R12, R13, and R14 are described in the specification. The invention also provides a method to prepare compound with formula (I), pharmaceutical composition containing such compounds and method to manufacture a medicament. These compounds are useful in the treatment of various CNS disorders, hematological disorders, eating disorders, diseases associated with pain, respiratory disease, genito-urological disorders, cardio vascular diseases and cancer.

  本发明描述了具有化学式(I)的3-(杂环)吲哚，其立体异构体和盐，其中取代基如R、R1、R2、R3、R4、R10、R11、R12、R13和R14在说明书中有所描述。该发明还提供了制备具有化学式(I)的化合物的方法，含有这些化合物的药物组合物以及制造药物的方法。这些化合物在治疗各种中枢神经系统疾病、血液学疾病、进食障碍、与疼痛相关的疾病、呼吸系统疾病、泌尿生殖系统疾病、心血管疾病和癌症方面具有用途。
• 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 and Structure Activity Relationship of Rigidized Indolyl Pyrrolidine Derivatives as 5-HT6 Receptor Ligands
  作者：Ramakrishna Nirogi、Adireddy Dwarampudi、Venugopalarao Bhatta、Laxman Kota、P.K. Dubey

  DOI：10.14233/ajchem.2013.15443

  日期：——

  A novel series of rigidized indolyl pyrrolidine derivatives have been designed by constraining the tryptamine nitrogen through a and b carbons. All the synthesized derivatives have shown moderate affinities at 5-HT6R when tested in in vitro binding assay. Synthesis, structure activity relationship (SAR), pharmacokinetic profile and in vivo efficacy of a selected compound is the subject matter of this communication.

  一系列新型刚性吲哚基吡咯烷衍生物通过限制色氨酸胺氮原子与a和b碳的结合而设计。所有合成的衍生物在体外结合测定中对5-HT6R表现出中等亲和力。本通讯的主题是选定化合物的合成、结构活性关系（SAR）、药代动力学特征以及体内疗效。