1-(4-氯苯基)-5-氧代吡咯烷-3-羧酸 | 39629-87-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: 1-(4-氯苯基)-5-氧代吡咯烷-3-羧酸
• 中文别名: 3-吡咯烷羧酸,1-(4-氯苯基)-5-氧代-；1-(4-氯-苯基)-5-氧代-吡咯烷-3-羧酸；1-(4-氯苯基)-5-氧代-3-吡咯烷羧酸
• 英文名称: 1-(4-chlorophenyl)-5-oxopyrrolidine-3-carboxylic acid
• CAS: 39629-87-3
• 化学式: C₁₁H₁₀ClNO₃
• mdl: MFCD00158023
• 分子量: 239.658
• InChiKey: QPYOMMCYFFZXIT-UHFFFAOYSA-N

物化性质

• 熔点：
  150-151 °C
• 沸点：
  540.8±45.0 °C(Predicted)
• 密度：
  1.455±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  16
• 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：
  3

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933790090
• 储存条件：
  室温

SDS

1-(4-氯-苯基)-5-氧代-吡咯烷-3-羧酸MSDS英文版

反应信息

• 作为反应物：
  描述：

  1-(4-氯苯基)-5-氧代吡咯烷-3-羧酸 在 甲醇 、 sodium hydroxide 、 sodium tetrahydroborate 、 硫酸 、 水 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 45.0h， 生成 methyl 1-(4-chlorophenyl)-5-oxo-pyrrolidine-3-acetate
  参考文献：
  名称：

  Synthesis of 4-[1-(substituted phenyl)-2-oxo-pyrrolidin-4-yl]methyloxybenzoic acids and related compounds, and their inhibitory capacities toward fatty-acid and sterol biosyntheses

  摘要：

  The synthesis of a series of 4[1-(substituted phenyl)-2-oxo-pyrrolidin-4-yl]methyloxybenzoic acids and related compounds, and their evaluation for inhibitory capacity toward fatty-acid and sterol biosyntheses using rats' liver slices in vitro and rabbits in vivo, are described. Among the compounds synthesized, 7e, 7g, 7h, 7i, 7k, 7r, 21, 23 and 29a b showed a potent inhibitory activity toward fatty-acid and sterol biosyntheses. Their IC(50)s were 4.4-6.8 x 10(-6) M and 6.6-9.8 x 10(-6) M, respectively. These activities were always superior to those of compounds I, II, III and Clinofibrate as references. The inhibitory activity toward the sterol biosynthesis of these compounds was inferior to that of Pravastatin. The reducing effects of the representative compounds (7e and 7l) toward plasma cholesterols and triglyceride were evaluated in Japanese white rabbits (30 and 100 mg/kg, po) and compared with those of Clinofibrate:and Pravastatin; The compounds showed a similar hypocholesterolemic effect to Pravastatin and a more potent hypotriglycemic effect than Clinofibrate and Pravastatin in this animal model. Thus, a dual,action of hypolipidemic effects was noted in 7e and 7l compared with the references.

  DOI：

  10.1016/0223-5234(94)90029-9
• 作为产物：
  描述：

  5-氧代-1-苯基吡咯烷-3-羧酸 在 苯基氯化硒 、 [双(三氟乙酰氧基)碘]苯 作用下， 以 二氯甲烷 为溶剂， 以67 %的产率得到1-(4-氯苯基)-5-氧代吡咯烷-3-羧酸
  参考文献：
  名称：

  无金属条件下芳烃和烯烃的区域选择性 C-H 硫属基化和卤化

  摘要：

  本文报道了在无导向基团和无金属条件下，PIFA作用下N-芳基吡咯烷酮的直接Csp 2 -H硫属基化和卤化反应。二苯基硒化物/硫和硒苯基卤化物用作反应试剂，分别得到硫属化和卤化的N-芳基吡咯烷酮产物。机理研究表明，这些反应可能涉及自由基途径。初步抗肿瘤试验表明，这些化合物在体外对人急性白血病细胞K562具有中强活性，可作为后续研究的先导化合物。

  DOI：

  10.1039/d3ob00150d

文献信息

• The discovery of new plant activators and scaffolds with potential induced systemic resistance: from jasmonic acid to pyrrolidone
  作者：Kang Chang、Yanxia Shi、Jianqin Chen、Zenghui He、Zheng Xu、Zhenjiang Zhao、Weiping Zhu、Honglin Li、Yufang Xu、BaoJu Li、Xuhong Qian

  DOI：10.1039/c6md00261g

  日期：——

  the JA pathway was rarely investigated for new plant activators. In this study, starting from JA and its analogs, based on the molecular three-dimensional shape and pharmacophore similarity comparison (SHAFTS), a new lead compound, pyrrolidone, as a new scaffold of plant activators was predicted and a series of 1-phenyl-5-pyrrolidone-3-carboxylic acid derivatives were designed and synthesized. The

  由于病原体，昆虫和某些特定微生物的感染，或者经过特定化学物质的处理，植物会发展出多方面的系统抗性。1其中，系统性获得性抵抗力（SAR）和诱导性系统抵抗力（ISR）2是两个最重要的类型。为了激活它们，已经基于SA途径开发了大量化学诱导剂。但是，对于新的植物激活剂，很少研究JA途径。在这项研究中，从JA及其类似物出发，基于分子三维形状和药效基团相似性比较（SHAFTS），预测了一种新的先导化合物吡咯烷酮，它将作为一种植物激活剂的新支架，并形成一系列1-苯基设计并合成了-5-吡咯烷酮-3-羧酸衍生物。对生物活性进行了评估，大多数化合物均显示出令人满意的活性。特别是化合物7-11在体外几乎没有显示 活性，但对被测疾病具有优异的疗效，并证实了虚拟筛选结果的预测，这促进了SHAFTS在农药开发中的应用。
• Synthesis of a novel and potent small-molecule antagonist of PAC1 receptor for the treatment of neuropathic pain
  作者：Ichiro Takasaki、Haruna Ogashi、Takuya Okada、Ayaka Shimodaira、Daichi Hayakawa、Ai Watanabe、Atsuro Miyata、Takashi Kurihara、Hiroaki Gouda、Naoki Toyooka

  DOI：10.1016/j.ejmech.2019.111902

  日期：2020.1

  identified novel small-molecule antagonists of the PACAP type I (PAC1) receptor using docking-based in silico screening followed by in vitro/vivo pharmacological assays. In the present study, we synthesized 18 novel derivatives based on the structure of PA-9, a recently developed antagonist of the PAC1 receptor, with a view to obtain a panel of compounds with more potent antagonistic and analgesic activities

  我们最近使用基于对接的计算机模拟筛选，然后进行体外/体内药理学鉴定，确定了PACAP I型（PAC1）受体的新型小分子拮抗剂。在本研究中，我们基于PA-9（一种最近开发的PAC1受体拮抗剂）的结构合成了18种新型衍生物，以期获得一组具有更强的拮抗和镇痛活性的化合物。其中，化合物3d显示出改善的拮抗活性。鞘内注射3d抑制垂体腺苷酸环化酶激活多肽（PACAP）和脊髓神经结扎诱导的机械性异常性疼痛。效果比PA-9更有效。口服给药后，化合物3d也显示出抗痛觉过敏作用。因此，
• [EN] INHIBITORS OF ARGINASE AND THEIR THERAPEUTIC APPLICATIONS<br/>[FR] INHIBITEURS D'ARGINASE ET LEURS APPLICATIONS THÉRAPEUTIQUES
  申请人：MARS INC

  公开号：WO2011133653A1

  公开（公告）日：2011-10-27

  Compounds according to Formula I and Formula II are potent inhibitors of Arginase I and II activity : Formule (I), (II) where R1, R2, R3, R4, R5, R6, R7, R8, R9, D, M, X, and Y are defined as set forth in the specification. The invention also provides pharmaceutical compositions of the compounds and methods of their use for treating or preventing a disease or a condition associated with arginase activity.

  根据式I和式II，化合物是Arginase I和II活性的强效抑制剂：式(I)，(II)中的R1、R2、R3、R4、R5、R6、R7、R8、R9、D、M、X和Y的定义如规范所述。该发明还提供了这些化合物的药物组合物以及它们用于治疗或预防与Arginase活性相关的疾病或病况的方法。
• Phenylcarboxylic acid derivatives having hetero ring
  申请人：Otsuka Pharmaceutical Company, Limited

  公开号：US05145865A1

  公开（公告）日：1992-09-08

  Phenylcarboxylic acid derivatives having a hetero ring in the substituent of the formula: ##STR1## wherein R.sup.1 is halogen, alkyl, cycloalkyl, hydroxy, alkoxy, phenoxy which has a substituent selected from halogen and alkyl, carboxyl, alkylsulfonyloxy, phenylsulfonyloxy optionally substituted by halogen, alkylsulfonyloxyalkoxy, amino, alkanoylamino, benzoylamino, alkenyloxy, phenylalkoxyalkoxy, hydroxyalkoxy, phenylalkoxy having optionally 1 to 3 substituents selected from halogen, alkyl and alkoxy, halogenoalkyl, cycloalkyloxy optionally substituted by hydroxy, alkoxy substituted by cycloalkyl having optionally hydroxy substituent, imidazolylalkyl or imidazolylalkoxy; k is 0 or 1 to 3; or (R.sup.1).sub.k is alkylenedioxy; A is alkylene or alkylenoxy; l is 0 or 1; B is methylene or carbonyl; m is 0 or 1; D is alkylene; E is alkylene or alkenylene; n is 0 or 1; and R.sup.2 is hydrogen or alkyl, or a salt thereof, which have fatty acid synthesis-inhibitory activity, cholesterol synthesis-inhibitory activity and are useful as antilipidemic agent, prophylactic and treating agent of arteriosclerosis, prophylactic and treating agent of obesity, antidiabetics.

  具有杂环取代基的苯甲酸衍生物的化学式：其中R.sup.1是卤素、烷基、环烷基、羟基、烷氧基、苯氧基，其取代基可选择自卤素和烷基、羧基、烷基磺酰氧基、苯基磺酰氧基，可选择地取代为卤素、烷基磺酰氧基烷氧基、氨基、烷酰胺基、苯甲酰胺基、烯烃氧基、苯基烷氧基烷氧基、羟基烷氧基、苯基烷氧基，其可选择地具有1至3个取代基，选自卤素、烷基和烷氧基、卤代烷基、环烷氧基，可选择地取代为羟基，烷氧基取代为环烷基，其可选择地具有羟基取代基，咪唑基烷基或咪唑基烷氧基；k为0或1至3；或（R.sup.1）.sub.k为亚烷二氧基；A为烷基或烷氧基；l为0或1；B为亚甲基或羰基；m为0或1；D为烷基；E为烷基或烯基；n为0或1；R.sup.2为氢或烷基，或其盐，具有脂肪酸合成抑制活性、胆固醇合成抑制活性并用作抗血脂药物、动脉粥样硬化的预防和治疗药物、肥胖症的预防和治疗药物、抗糖尿病药物。
• 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）。