tert-butyl 1-(4-bromo-2-fluorobenzyl)-2-oxospiro[indoline-3,3'-pyrrolidine]-1'-carboxylate | 1426689-05-5

• 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: tert-butyl 1-(4-bromo-2-fluorobenzyl)-2-oxospiro[indoline-3,3'-pyrrolidine]-1'-carboxylate
• 英文别名: Tert-butyl 1-[(4-bromo-2-fluorophenyl)methyl]-2-oxospiro[indole-3,3'-pyrrolidine]-1'-carboxylate；tert-butyl 1-[(4-bromo-2-fluorophenyl)methyl]-2-oxospiro[indole-3,3'-pyrrolidine]-1'-carboxylate
• CAS: 1426689-05-5
• 化学式: C₂₃H₂₄BrFN₂O₃
• 分子量: 475.358
• InChiKey: GVHIGZQCVSGCDF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 1-(4-bromo-2-fluorobenzyl)-2-oxospiro[indoline-3,3'-pyrrolidine]-1'-carboxylate 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 caesium carbonate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 0.17h， 生成 1-(2-fluoro-4-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)benzyl)spiro[indoline-3,3'-pyrrolidin]-2-one
  参考文献：
  名称：

  Spirocyclic replacements for the isatin in the highly selective, muscarinic M1 PAM ML137: The continued optimization of an MLPCN probe molecule

  摘要：

  This Letter describes the further optimization of an MLPCN probe molecule (ML137) through the introduction of 5- and 6-membered spirocycles in place of the isatin ketone. Interestingly divergent structure-activity relationships, when compared to earlier M-1 PAMs, are presented. These novel spirocycles possess improved efficacy relative to ML137, while also maintaining high selectivity for the human and rat muscarinic M-1 receptor subtype. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.01.017
• 作为产物：
  描述：

  4-溴-2-氟苄溴 、 2-氧代-1,2-二氢螺[吲哚-3,3-吡咯烷]-1-羧酸叔丁酯 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 生成 tert-butyl 1-(4-bromo-2-fluorobenzyl)-2-oxospiro[indoline-3,3'-pyrrolidine]-1'-carboxylate
  参考文献：
  名称：

  SUBSTITUTED BENZYLSPIROINDOLIN-2-ONE ANALOGS AS POSITIVE ALLOSTERIC MODULATORS OF THE MUSCARINIC ACETYLCHOLINE RECEPTOR M1

  摘要：

  在一个方面，该发明涉及替代苯基螺合吲哚啉-2-酮类似物化合物，其衍生物和相关化合物，这些化合物可用作肌胆碱受体M1(mAChR M1)的正向变构调节剂；制备这些化合物的合成方法；包含这些化合物的药物组合物；以及使用这些化合物和组合物治疗与肌胆碱受体功能障碍相关的神经系统和精神疾病的方法。本摘要旨在作为特定领域搜索的扫描工具，并不意在限制本发明。

  公开号：

  US20130123236A1

文献信息

• SUBSTITUTED BENZYLSPIROINDOLIN-2-ONE ANALOGS AS POSITIVE ALLOSTERIC MODULATORS OF THE MUSCARINIC ACETYLCHOLINE RECEPTOR M1
  申请人：VANDERBILT UNIVERSITY

  公开号：US20130123236A1

  公开（公告）日：2013-05-16

  In one aspect, the invention relates to substituted benzylspiroindolin-2-one analogs compounds, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M 1 (mAChR M 1 ); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  在一个方面，该发明涉及替代苯基螺合吲哚啉-2-酮类似物化合物，其衍生物和相关化合物，这些化合物可用作肌胆碱受体M1(mAChR M1)的正向变构调节剂；制备这些化合物的合成方法；包含这些化合物的药物组合物；以及使用这些化合物和组合物治疗与肌胆碱受体功能障碍相关的神经系统和精神疾病的方法。本摘要旨在作为特定领域搜索的扫描工具，并不意在限制本发明。
• US9073935B2
  申请人：——

  公开号：US9073935B2

  公开（公告）日：2015-07-07
• [EN] SUBSTITUTED BENZYLSPIROINDOLIN-2-ONE ANALOGS AS POSITIVE ALLOSTERIC MODULATORS OF THE MUSCARINIC ACETYLCHOLINE RECEPTOR M1<br/>[FR] ANALOGUES DE BENZYLSPIROINDOLIN-2-ONE SUBSTITUÉE UTILISABLES COMME MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR MUSCARINIQUE M1 DE L'ACÉTYLCHOLINE
  申请人：UNIV VANDERBILT

  公开号：WO2013071201A1

  公开（公告）日：2013-05-16

  In one aspect, the invention relates to substituted benzylspiroindolin-2-one analogs compounds, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor Mi (mAChR M1); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
• Spirocyclic replacements for the isatin in the highly selective, muscarinic M1 PAM ML137: The continued optimization of an MLPCN probe molecule
  作者：Michael S. Poslusney、Bruce J. Melancon、Patrick R. Gentry、Douglas J. Sheffler、Thomas M. Bridges、Thomas J. Utley、J. Scott Daniels、Colleen M. Niswender、P. Jeffrey Conn、Craig W. Lindsley、Michael R. Wood

  DOI：10.1016/j.bmcl.2013.01.017

  日期：2013.3

  This Letter describes the further optimization of an MLPCN probe molecule (ML137) through the introduction of 5- and 6-membered spirocycles in place of the isatin ketone. Interestingly divergent structure-activity relationships, when compared to earlier M-1 PAMs, are presented. These novel spirocycles possess improved efficacy relative to ML137, while also maintaining high selectivity for the human and rat muscarinic M-1 receptor subtype. (C) 2013 Elsevier Ltd. All rights reserved.