(2S,4R)-1-((R)-5-chloro-3-(2-methoxyphenyl)-2-oxoindolin-3-yl)-4-hydroxy-N,N-dimethylpyrrolidine-2-carboxamide | 352278-36-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S,4R)-1-((R)-5-chloro-3-(2-methoxyphenyl)-2-oxoindolin-3-yl)-4-hydroxy-N,N-dimethylpyrrolidine-2-carboxamide
• 英文别名: (2S,4R)-1-[(3R)-5-chloro-3-(2-methoxyphenyl)-2-oxo-1H-indol-3-yl]-4-hydroxy-N,N-dimethylpyrrolidine-2-carboxamide
• CAS: 352278-36-5
• 化学式: C₂₂H₂₄ClN₃O₄
• 分子量: 429.903
• InChiKey: WRNVMCWBWWYGLM-GHNFSYLKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  82.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,4-二甲氧基苯磺酰氯 、 (2S,4R)-1-((R)-5-chloro-3-(2-methoxyphenyl)-2-oxoindolin-3-yl)-4-hydroxy-N,N-dimethylpyrrolidine-2-carboxamide 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.05h， 以100%的产率得到(4R)-1-[(3R)-5-氯-1-[(2,4-二甲氧基苯基)磺酰基]-3-(2-甲氧基苯基)-2-氧代-2,3-二氢-1H-吲哚-3-基]-4-羟基-N,N-二甲基-L-脯氨酰胺
  参考文献：
  名称：

  Synthesis of [11C]SSR149415 and preliminary imaging studies using positron emission tomography

  摘要：

  SSR149415 was the first non-peptide vasopressin-(V-1b) receptor antagonist reported. It has been used to probe the role of V-1b receptors in animal models of depression, aggression, and stress-anxiety, and was progressed to clinical trials for the treatment of depression. Due to the interest in V-1b receptors as a therapeutic target and the growing use of SSR149415 in preclinical research, we developed a method to label SSR145419 with carbon-11 and have studied its pharmacokinetics in non-human primates using positron emission tomography. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.03.108
• 作为产物：
  描述：

  2-Methoxyphenylmagnesium bromide 在 吡啶 、 氯化亚砜 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (2S,4R)-1-((S)-5-chloro-3-(2-methoxyphenyl)-2-oxoindolin-3-yl)-4-hydroxy-N,N-dimethylpyrrolidine-2-carboxamide 、 (2S,4R)-1-((R)-5-chloro-3-(2-methoxyphenyl)-2-oxoindolin-3-yl)-4-hydroxy-N,N-dimethylpyrrolidine-2-carboxamide
  参考文献：
  名称：

  Potent and selective oxindole-based vasopressin 1b receptor antagonists with improved pharmacokinetic properties

  摘要：

  Herein we report the discovery of a novel series of vasopressin 1b (V1b) receptor antagonists, starting from potent but metabolically labile oxindole SSR149415. Masking the proline N,N-dimethyl amide moiety as an oxazole and attaching a benzylic amine moiety to the northern phenyl ring resulted in potent and selective V1b receptor antagonists with improved metabolic stability and improved pharmacokinetic properties in rat. Compound 18c was found to be efficacious in a rat model of anti-depressant activity. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.03.012

文献信息

• Bioo. Med. Chem. Lett. 2010, 20, 3103-3106
  作者：

  DOI：——

  日期：——
• Potent and selective oxindole-based vasopressin 1b receptor antagonists with improved pharmacokinetic properties
  作者：Thorsten Oost、Gisela Backfisch、Swati Bhowmik、Marcel M. van Gaalen、Hervé Geneste、Wilfried Hornberger、Wilfried Lubisch、Astrid Netz、Liliane Unger、Wolfgang Wernet

  DOI：10.1016/j.bmcl.2011.03.012

  日期：2011.6

  Herein we report the discovery of a novel series of vasopressin 1b (V1b) receptor antagonists, starting from potent but metabolically labile oxindole SSR149415. Masking the proline N,N-dimethyl amide moiety as an oxazole and attaching a benzylic amine moiety to the northern phenyl ring resulted in potent and selective V1b receptor antagonists with improved metabolic stability and improved pharmacokinetic properties in rat. Compound 18c was found to be efficacious in a rat model of anti-depressant activity. (C) 2011 Elsevier Ltd. All rights reserved.
• Synthesis of [11C]SSR149415 and preliminary imaging studies using positron emission tomography
  作者：Matthias Schönberger、Carmine Leggett、Sung Won Kim、Jacob M. Hooker

  DOI：10.1016/j.bmcl.2010.03.108

  日期：2010.5

  SSR149415 was the first non-peptide vasopressin-(V-1b) receptor antagonist reported. It has been used to probe the role of V-1b receptors in animal models of depression, aggression, and stress-anxiety, and was progressed to clinical trials for the treatment of depression. Due to the interest in V-1b receptors as a therapeutic target and the growing use of SSR149415 in preclinical research, we developed a method to label SSR145419 with carbon-11 and have studied its pharmacokinetics in non-human primates using positron emission tomography. (C) 2010 Elsevier Ltd. All rights reserved.