3-Methyl-4-(2-oxopyrrolidin-1-YL)benzonitrile | 1260802-45-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 3-Methyl-4-(2-oxopyrrolidin-1-YL)benzonitrile
• CAS: 1260802-45-6
• 化学式: C₁₂H₁₂N₂O
• 分子量: 200.24
• InChiKey: UREKXLKLQHAGIT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-Methyl-4-(2-oxopyrrolidin-1-YL)benzonitrile 、 3-氨基巴豆酸乙酯 在 三氯氧磷 作用下， 以 1,2-二氯乙烷 为溶剂， 生成
  参考文献：
  名称：

  Synthesis and Pharmacological Characterization of Novel Druglike Corticotropin-Releasing Factor 1 Antagonists

  摘要：

  To identify new CRF1 receptor antagonists, an attempt to modify the bis-hetherocycle moiety present in the top region of the dihydropirrole[2,3]pyridine template was made following new pharmacophoric hypothesis on the CRF1 receptor antagonists binding pocket. In particular, the 2-thiazole ring, present in the previous series of compounds, was replaced by more hydrophilic non aromatic hetherocycles able to make appropriate H-bond interactions with amino acid residues Thr192 and Tyr195. This exploration, followed by an accurate analysis of the substitution of the pendant aryl ring, enabled to identify in vitro potent compounds showing excellent pharmacokinetics and outstanding in vivo activity in animal models of anxiety, both in rodents and primates.

  DOI：

  10.1021/jm800744m
• 作为产物：
  描述：

  4-chloro-N-(4-cyano-2-methylphenyl)butanamide 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 生成 3-Methyl-4-(2-oxopyrrolidin-1-YL)benzonitrile
  参考文献：
  名称：

  Synthesis and Pharmacological Characterization of Novel Druglike Corticotropin-Releasing Factor 1 Antagonists

  摘要：

  To identify new CRF1 receptor antagonists, an attempt to modify the bis-hetherocycle moiety present in the top region of the dihydropirrole[2,3]pyridine template was made following new pharmacophoric hypothesis on the CRF1 receptor antagonists binding pocket. In particular, the 2-thiazole ring, present in the previous series of compounds, was replaced by more hydrophilic non aromatic hetherocycles able to make appropriate H-bond interactions with amino acid residues Thr192 and Tyr195. This exploration, followed by an accurate analysis of the substitution of the pendant aryl ring, enabled to identify in vitro potent compounds showing excellent pharmacokinetics and outstanding in vivo activity in animal models of anxiety, both in rodents and primates.

  DOI：

  10.1021/jm800744m

文献信息

• Synthesis and Pharmacological Characterization of Novel Druglike Corticotropin-Releasing Factor 1 Antagonists
  作者：Romano Di Fabio、Yves St-Denis、Fabio M. Sabbatini、Daniele Andreotti、Roberto Arban、Giovanni Bernasconi、Simone Braggio、Frank E. Blaney、Anna M. Capelli、Emiliano Castiglioni、Enza Di Modugno、Daniele Donati、Elettra Fazzolari、Emiliangelo Ratti、Aldo Feriani、Stefania Contini、Gabriella Gentile、Damiano Ghirlanda、Stefano Provera、Carla Marchioro、Karen L. Roberts、Anna Mingardi、Mario Mattioli、Arnaldo Nalin、Francesca Pavone、Simone Spada、David G. Trist、Angela Worby

  DOI：10.1021/jm800744m

  日期：2008.12.11

  To identify new CRF1 receptor antagonists, an attempt to modify the bis-hetherocycle moiety present in the top region of the dihydropirrole[2,3]pyridine template was made following new pharmacophoric hypothesis on the CRF1 receptor antagonists binding pocket. In particular, the 2-thiazole ring, present in the previous series of compounds, was replaced by more hydrophilic non aromatic hetherocycles able to make appropriate H-bond interactions with amino acid residues Thr192 and Tyr195. This exploration, followed by an accurate analysis of the substitution of the pendant aryl ring, enabled to identify in vitro potent compounds showing excellent pharmacokinetics and outstanding in vivo activity in animal models of anxiety, both in rodents and primates.