4-(benzo[d]oxazol-2-yl)-1-phenylpyrrolidin-2-one

• 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: 4-(benzo[d]oxazol-2-yl)-1-phenylpyrrolidin-2-one
• 英文别名: 4-(1,3-Benzoxazol-2-yl)-1-phenylpyrrolidin-2-one；4-(1,3-benzoxazol-2-yl)-1-phenylpyrrolidin-2-one
• 化学式: C₁₇H₁₄N₂O₂
• 分子量: 278.31
• InChiKey: FEGSQBGFHORSMQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  46.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  5-氧代-1-苯基吡咯烷-3-羧酸 、 2-氨基苯酚 反应 2.5h， 以60%的产率得到4-(benzo[d]oxazol-2-yl)-1-phenylpyrrolidin-2-one
  参考文献：
  名称：

  1-芳基-4-羧基-2-吡咯烷酮与邻二氨基芳烃、邻氨基苯酚的缩合产物及其结构研究

  摘要：

  通过1-芳基-4-羧基-2-吡咯烷酮与芳香族邻二胺或邻氨基苯酚的缩合反应合成了一系列2-取代苯并咪唑、苯并恶唑。苯并咪唑与碘代烷烃的烷基化产生 1-芳基-4-(1-烷基-1H-苯并咪唑-2-基)-2-吡咯烷酮或 1,3-二烷基苯并咪唑鎓碘化物。N-取代的γ-氨基酸是通过1-芳基-4-(1H-苯并咪唑-2-基)-2-吡咯烷酮在氢氧化钠溶液中水解制备的，然后用乙酸处理。使用 IR 和 1H、13C NMR 光谱、MM2 分子力学和 AM1 半经验量子力学方法研究了合成产物的结构。© 2006 Wiley Periodicals, Inc. 杂原子化学 17:47–56, 2006; 在线发表于 Wiley InterScience (www.interscience.wiley.com)。DOI 10.1002/hc.20171

  DOI：

  10.1002/hc.20171

文献信息

• Efficient novel eutectic-mixture-mediated synthesis of benzoxazole-linked pyrrolidin-2-one heterocycles
  作者：Yassine Riadi、Oussama Ouerghi、Mohammed H. Geesi、Abdellah Kaiba、El Hassane Anouar、Philippe Guionneau

  DOI：10.1016/j.molliq.2020.115011

  日期：2021.2

  infrared spectroscopy were employed to investigate the structure of the ionic liquid and characterize the DES, respectively. This method exhibited key advantages of high productivity, a short reaction time, and simple processing. Moreover, this DES was easily separated from reaction mixtures and can be recycled for multiple reactions.

  在这项研究中，在新设计的无金属深共熔溶剂（DES）的存在下，采用取代的苄胺和2-氨基苯酚，通过生态高效策略合成了新的苯并恶唑连接的吡咯烷酮杂环化合物。通过使用尿素和合成的甘氨酸衍生的离子液体的低共熔混合物来制备该DES。X射线衍射和红外光谱法分别用于研究离子液体的结构和表征DES。 该方法显示出高生产率，短反应时间和简单加工的主要优点。此外，该DES易于从反应混合物中分离出来，并可循环用于多个反应。
• Condensation products of 1-aryl-4-carboxy- 2- pyrrolidinones witho-diaminoarenes,o-aminophenol, and their structural studies
  作者：Marius Mickevicius、Zigmuntas Jonas Beresnevicius、Vytautas Mickevicius、Gema Mikulskiene

  DOI：10.1002/hc.20171

  日期：——

  A series of 2-substituted benzimidazoles, benzoxazoles were synthesized by the condensation reactions of 1-aryl-4-carboxy-2-pyrrolidinones and aromatic ortho-diamines or ortho-aminophenol. Alkylation of benzimidazoles with iodoalkanes led to 1-aryl-4-(1-alkyl-1H-benzimidazol-2-yl)-2-pyrrolidin- ones or 1,3-dialkylbenzimidazolium iodides. N-Subs- tituted γ-amino acids were prepared by the hydrolysis

  通过1-芳基-4-羧基-2-吡咯烷酮与芳香族邻二胺或邻氨基苯酚的缩合反应合成了一系列2-取代苯并咪唑、苯并恶唑。苯并咪唑与碘代烷烃的烷基化产生 1-芳基-4-(1-烷基-1H-苯并咪唑-2-基)-2-吡咯烷酮或 1,3-二烷基苯并咪唑鎓碘化物。N-取代的γ-氨基酸是通过1-芳基-4-(1H-苯并咪唑-2-基)-2-吡咯烷酮在氢氧化钠溶液中水解制备的，然后用乙酸处理。使用 IR 和 1H、13C NMR 光谱、MM2 分子力学和 AM1 半经验量子力学方法研究了合成产物的结构。© 2006 Wiley Periodicals, Inc. 杂原子化学 17:47–56, 2006; 在线发表于 Wiley InterScience (www.interscience.wiley.com)。DOI 10.1002/hc.20171
• 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）。