1-(3-chloro-4-fluorophenyl)-5-oxopyrrolidine-3-carboxylic acid | 696647-51-5

• 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: 1-(3-chloro-4-fluorophenyl)-5-oxopyrrolidine-3-carboxylic acid
• CAS: 696647-51-5
• 化学式: C₁₁H₉ClFNO₃
• mdl: MFCD03834520
• 分子量: 257.649
• InChiKey: BMPMCEJUODXJTL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.272
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  1-(3-chloro-4-fluorophenyl)-5-oxopyrrolidine-3-carboxylic acid 在 sodium tetrahydroborate 、 碘 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以85%的产率得到[1-(3-chloro-4-fluorophenyl)pyrrolidin-3-yl]methanol
  参考文献：
  名称：

  Sodium borohydride–iodine mediated reduction of γ-lactam carboxylic acids followed by DDQ mediated oxidative aromatisation: a simple approach towards N-aryl-formylpyrroles and 1,3-diaryl-formylpyrroles

  摘要：

  A simple methodology for the conversion of substituted N-aryl-gamma-lactam 2/3-carboxylic acids to substituted N-aryl-2/3-formyl-pyrroles has been developed. Several N-aryl-gamma-lactam 2/3-carboxylic acids were reduced to substituted (N-aryl-pyrroliden-2/3-yl)-methanols in good yields by using the NaBH4-I-2 system. Aromatisation and in situ oxidation of these alcohols using DDQ produced N-aryl-2/3-formyl-pyrroles, which act as key starting material and intermediates in the synthesis of several bioactive compounds. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2007.01.058
• 作为产物：
  描述：

  3-氯-4-氟苯胺 、 衣康酸 生成 1-(3-chloro-4-fluorophenyl)-5-oxopyrrolidine-3-carboxylic acid
  参考文献：
  名称：

  Analgesic and Anticancer Activity of Benzoxazole Clubbed 2-Pyrrolidinones as Novel Inhibitors of Monoacylglycerol Lipase

  摘要：

  设计了十种苯并噁唑与2-吡咯酮结合的人类单酰甘油酶抑制剂（11-20），根据先前报道的抑制剂的结构要求和基础设计。设计、合成和表征的化合物（11-20）针对单酰甘油酶（MAGL）进行筛选，以寻找潜在的抑制剂。化合物19（4-NO2衍生物）和20（4-SO2NH2衍生物）的IC50值分别为8.4和7.6 nM，是最活跃的。它们对于一个相似的分子，脂肪酸酰胺水解酶（FAAH），显示出微摩尔级别的活性（IC50值大于50µM），因此被认为是MAGL的选择性抑制剂。化合物19和20的分子对接研究表明，2-吡咯酮结构中的酰基位于酶的催化位点的氧酰离子孔中，与负责酶催化功能的氨基酸残基Ala51、Met123和Ser122形成三个氢键（约2埃）。值得注意的是，通过QikProp计算，化合物19和20的理化和药代性质符合良好口服生物活性中枢神经系统药物的建议指南。在甲醛诱导的疼痛实验中，化合物20以剂量依赖方式减少了急性和迟发性阶段的疼痛反应。它们显著地减少了疼痛反应，比阳性对照加巴喷丁（GBP）在30毫克/千克剂量下具有更好的效力。化合物19和20被提交给美国国家癌症研究所（NCI）进行抗癌活性筛选。化合物19（NSC：778839）和20（NSC：778842）在中枢神经系统癌症SNB-75细胞系上表现出良好的抗癌活性，分别显示出35.49%和31.88%的生长抑制率（%GI）。

  DOI：

  10.3390/molecules26082389

文献信息

• Pyrrolidin‐2‐one linked benzofused heterocycles as novel small molecule monoacylglycerol lipase inhibitors and antinociceptive agents
  作者：Abdulmalik Saleh Alfawaz Altamimi、Sandhya Bawa、Fareeda Athar、Md Quamrul Hassan、Yassine Riadi、Obaid Afzal

  DOI：10.1111/cbdd.13751

  日期：2020.12

  Eighteen pyrrolidin‐2‐one linked benzothiazole, and benzimidazole derivatives (10–27 ) were designed and synthesized. The structure of the compounds was confirmed by elemental and spectral (IR, 1H‐NMR and MS) data analysis. All the compounds were screened by human monoacylglycerol lipase (h MAGL) inhibition assay. Three benzimidazole compounds, 22 (4‐Cl phenyl), 23 (3‐Cl,4‐F phenyl) and 25 (4‐methoxy

  设计并合成了十八种吡咯烷-2-酮连接的苯并噻唑和苯并咪唑衍生物 ( 10-27 )。通过元素和光谱（IR、1 H-NMR 和 MS）数据分析确认了化合物的结构。所有化合物均通过人单酰基甘油脂肪酶（h MAGL）抑制试验进行筛选。发现三种苯并咪唑化合物22（4-Cl 苯基）、23（3-Cl,4-F 苯基）和25（4-甲氧基苯基）最有效，IC 50值为 8.6、8.0 和 9.4 n m，分别。其中，卤素取代的苯基衍生物，化合物22（4-Cl 苯基）和化合物23（3-氯，4-F苯基），显示出微摩尔效力对脂肪酸酰胺水解酶（FAAH），具有IC 50的35和24μ值米，分别。苯并咪唑衍生物具有4-甲氧基苯基取代（化合物25）被发现是一种选择性抑制剂MAGL（IC 50  = 9.4Ñ米），与IC 50值在50以上μ米对FAAH。在福尔马林诱导的伤害感受试验中，化合物25在急性期和晚期均表现出剂量依赖性的疼痛反应降低。在
• Sodium borohydride–iodine mediated reduction of γ-lactam carboxylic acids followed by DDQ mediated oxidative aromatisation: a simple approach towards N-aryl-formylpyrroles and 1,3-diaryl-formylpyrroles
  作者：Pranab Haldar、Gopa Barman、Jayanta K. Ray

  DOI：10.1016/j.tet.2007.01.058

  日期：2007.4

  A simple methodology for the conversion of substituted N-aryl-gamma-lactam 2/3-carboxylic acids to substituted N-aryl-2/3-formyl-pyrroles has been developed. Several N-aryl-gamma-lactam 2/3-carboxylic acids were reduced to substituted (N-aryl-pyrroliden-2/3-yl)-methanols in good yields by using the NaBH4-I-2 system. Aromatisation and in situ oxidation of these alcohols using DDQ produced N-aryl-2/3-formyl-pyrroles, which act as key starting material and intermediates in the synthesis of several bioactive compounds. (c) 2007 Elsevier Ltd. All rights reserved.
• Analgesic and Anticancer Activity of Benzoxazole Clubbed 2-Pyrrolidinones as Novel Inhibitors of Monoacylglycerol Lipase
  作者：Obaid Afzal、Abdulmalik Saleh Alfawaz Altamimi、Mir Mohammad Shahroz、Hemant Kumar Sharma、Yassine Riadi、Md Quamrul Hassan

  DOI：10.3390/molecules26082389

  日期：——

  Ten benzoxazole clubbed 2-pyrrolidinones (11–20) as human monoacylglycerol lipase inhibitors were designed on the criteria fulfilling the structural requirements and on the basis of previously reported inhibitors. The designed, synthesized, and characterized compounds (11–20) were screened against monoacylglycerol lipase (MAGL) in order to find potential inhibitors. Compounds 19 (4-NO2 derivative) and 20 (4-SO2NH2 derivative), with an IC50 value of 8.4 and 7.6 nM, were found most active, respectively. Both of them showed micromolar potency (IC50 value above 50 µM) against a close analogue, fatty acid amide hydrolase (FAAH), therefore considered as selective inhibitors of MAGL. Molecular docking studies of compounds 19 and 20 revealed that carbonyl of 2-pyrrolidinone moiety sited at the oxyanion hole of catalytic site of the enzyme stabilized with three hydrogen bonds (~2 Å) with Ala51, Met123, and Ser122, the amino acid residues responsible for the catalytic function of the enzyme. Remarkably, the physiochemical and pharmacokinetic properties of compounds 19 and 20, computed by QikProp, were found to be in the qualifying range as per the proposed guideline for good orally bioactive CNS drugs. In formalin-induced nociception test, compound 20 reduced the pain response in acute and late stages in a dose-dependent manner. They significantly demonstrated the reduction in pain response, having better potency than the positive control gabapentin (GBP), at 30 mg/kg dose. Compounds 19 and 20 were submitted to NCI, USA, for anticancer activity screening. Compounds 19 (NSC: 778839) and 20 (NSC: 778842) were found to have good anticancer activity on SNB-75 cell line of CNS cancer, exhibiting 35.49 and 31.88% growth inhibition (% GI), respectively.

  设计了十种苯并噁唑与2-吡咯酮结合的人类单酰甘油酶抑制剂（11-20），根据先前报道的抑制剂的结构要求和基础设计。设计、合成和表征的化合物（11-20）针对单酰甘油酶（MAGL）进行筛选，以寻找潜在的抑制剂。化合物19（4-NO2衍生物）和20（4-SO2NH2衍生物）的IC50值分别为8.4和7.6 nM，是最活跃的。它们对于一个相似的分子，脂肪酸酰胺水解酶（FAAH），显示出微摩尔级别的活性（IC50值大于50µM），因此被认为是MAGL的选择性抑制剂。化合物19和20的分子对接研究表明，2-吡咯酮结构中的酰基位于酶的催化位点的氧酰离子孔中，与负责酶催化功能的氨基酸残基Ala51、Met123和Ser122形成三个氢键（约2埃）。值得注意的是，通过QikProp计算，化合物19和20的理化和药代性质符合良好口服生物活性中枢神经系统药物的建议指南。在甲醛诱导的疼痛实验中，化合物20以剂量依赖方式减少了急性和迟发性阶段的疼痛反应。它们显著地减少了疼痛反应，比阳性对照加巴喷丁（GBP）在30毫克/千克剂量下具有更好的效力。化合物19和20被提交给美国国家癌症研究所（NCI）进行抗癌活性筛选。化合物19（NSC：778839）和20（NSC：778842）在中枢神经系统癌症SNB-75细胞系上表现出良好的抗癌活性，分别显示出35.49%和31.88%的生长抑制率（%GI）。