3-(4-chlorophenyl)pyrrolidin-2-one | 120418-69-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯啉
• 英文名称: 3-(4-chlorophenyl)pyrrolidin-2-one
• CAS: 120418-69-1
• 化学式: C₁₀H₁₀ClNO
• 分子量: 195.648
• InChiKey: XUHZYYCMBOYAHK-UHFFFAOYSA-N

物化性质

• 沸点：
  390.0±42.0 °C(Predicted)
• 密度：
  1.243±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3-(4-chlorophenyl)pyrrolidin-2-one 在 盐酸 作用下， 以 水 为溶剂， 反应 11.0h， 以54%的产率得到2-(4-氯苯基)-4-氨基丁酸
  参考文献：
  名称：

  Metabolism of 3-(p-chlorophenyl)pyrrolidine. Structural effects in conversion of a prototype .gamma.-aminobutyric acid prodrug to lactam and .gamma.-aminobutyric acid type metabolites

  摘要：

  By use of rat liver or brain homogenate supernatants containing microsomes and/or mitochondria, it was found that the prototype GABAergic prodrug [3-(p-chlorophenyl)pyrrolidine (1)] underwent a series of alpha-oxidation transformations to a pair of amino acid metabolites and a pair of lactam metabolites [4-amino-3-(p-chlorophenyl)butanoic acid, baclofen (5); 4-amino-2-(p-chlorophenyl)butanoic acid (10); 4-(chlorophenyl)pyrrolidin-2-one and 3-(p-chlorophenyl)pyrrolidine-2-one (11)]. With the liver homogenates, the formation of the lactam metabolites was approximately 2 orders of magnitude greater than that of the amino acid metabolites, while with the brain homogenates, the amino acid and lactam pathways were of similar magnitude. For either tissue, for both the lactam and the amino acid series, attack at the less sterically hindered 5-position of the pyrrolidine ring was greater than the attack at the 2-position (5 greater than 10 and 6 greater than 11) with the exception of the liver homogenate mitochondrial fraction (6 less than 11). The parenteral administration of the prodrug 1 was found to give detectable brain levels of 5 as well as activity in an isoniazid-induced (GABA-inhibited) convulsion model.

  DOI：

  10.1021/jm00126a033
• 作为产物：
  描述：

  对氯苯乙酸乙酯 在 镍 氢气 、 苄基三甲基氢氧化铵 作用下， 以 甲醇 、 乙醇 、 xylene 为溶剂， 25.0~70.0 ℃ 、12.41 MPa 条件下， 反应 2.0h， 生成 3-(4-chlorophenyl)pyrrolidin-2-one
  参考文献：
  名称：

  Metabolism of 3-(p-chlorophenyl)pyrrolidine. Structural effects in conversion of a prototype .gamma.-aminobutyric acid prodrug to lactam and .gamma.-aminobutyric acid type metabolites

  摘要：

  By use of rat liver or brain homogenate supernatants containing microsomes and/or mitochondria, it was found that the prototype GABAergic prodrug [3-(p-chlorophenyl)pyrrolidine (1)] underwent a series of alpha-oxidation transformations to a pair of amino acid metabolites and a pair of lactam metabolites [4-amino-3-(p-chlorophenyl)butanoic acid, baclofen (5); 4-amino-2-(p-chlorophenyl)butanoic acid (10); 4-(chlorophenyl)pyrrolidin-2-one and 3-(p-chlorophenyl)pyrrolidine-2-one (11)]. With the liver homogenates, the formation of the lactam metabolites was approximately 2 orders of magnitude greater than that of the amino acid metabolites, while with the brain homogenates, the amino acid and lactam pathways were of similar magnitude. For either tissue, for both the lactam and the amino acid series, attack at the less sterically hindered 5-position of the pyrrolidine ring was greater than the attack at the 2-position (5 greater than 10 and 6 greater than 11) with the exception of the liver homogenate mitochondrial fraction (6 less than 11). The parenteral administration of the prodrug 1 was found to give detectable brain levels of 5 as well as activity in an isoniazid-induced (GABA-inhibited) convulsion model.

  DOI：

  10.1021/jm00126a033

文献信息

• Asymmetric Michael Addition Reaction of α-Aryl-Substituted Lactams Catalyzed by Chiral Quaternary Ammonium Salts Derived from Cinchona Alkaloids: A New Short Synthesis of (+)-Mesembrine
  作者：Hiyoshizo Kotsuki、Shiori Nunokawa、Masamitsu Minamisawa、Keiji Nakano、Yoshiyasu Ichikawa

  DOI：10.1055/s-0035-1560090

  日期：——

  The enantioselective Michael addition reaction of α-aryl-substituted lactams with electron-deficient olefins was efficiently catalyzed using chiral quaternary ammonium salts derived from cinchona alkaloids. This method was highly useful for the construction of an all-carbon-substituted quaternary carbon stereogenic center at the α-position of lactams in good to high yields and with good enantiomeric

  α-芳基取代的内酰胺与缺电子烯烃的对映选择性迈克尔加成反应使用金鸡纳生物碱衍生的手性季铵盐有效催化。该方法对于在内酰胺的 α 位构建全碳取代的季碳立体中心非常有用，收率良好，对映体过量良好，可应用于 (+)-mesembrine 的短程合成.
• [EN] MODULATORS OF THE INTEGRATED STRESS PATHWAY<br/>[FR] MODULATEURS DE LA VOIE DE RÉPONSE INTÉGRÉE AU STRESS
  申请人：CALICO LIFE SCIENCES LLC

  公开号：WO2022094244A1

  公开（公告）日：2022-05-05

  Provided herein are compounds, compositions, and methods useful for modulating the integrated stress response (I SR) and for treating related diseases, disorders, and conditions.

  本文提供了一些化合物、组合物和方法，用于调节综合应激反应（ISR）和治疗相关疾病、疾患和病况。
• [EN] SUBSTITUTED CYCLOALKYLS AS MODULATORS OF THE INTEGRATED STRESS PATHWAY<br/>[FR] CYCLOALKYLES SUBSTITUÉS UTILISÉS EN TANT QUE MODULATEURS DE LA VOIE INTÉGRÉE AU STRESS
  申请人：CALICO LIFE SCIENCES LLC

  公开号：WO2020223538A8

  公开（公告）日：2021-11-18
• SUBSTITUTED CYCLOALKYLS AS MODULATORS OF THE INTEGRATED STRESS PATHWAY
  申请人：Calico Life Sciences LLC

  公开号：EP3962906A1

  公开（公告）日：2022-03-09
• TRICYCLIC DERIVATIVE
  申请人：Sunovion Pharmaceuticals Inc.

  公开号：US20170273985A1

  公开（公告）日：2017-09-28

  Disclosed are compounds useful as inhibitors of phosphodiesterase 1 (PDE1), compositions thereof, and methods of using the same.