1-(4-羟基-苯基)-5-氧代-吡咯烷-3-羧酸 | 39629-88-4

• 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-羟基-苯基)-5-氧代-吡咯烷-3-羧酸
• 中文别名: 1-(4-羟苯基)-5-氧代-吡咯烷-3-羧酸；1-(4-羟苯基)-5-氧代-3-吡咯烷羧酸
• 英文名称: 1-(4-hydroxyphenyl)-5-oxopyrrolidine-3-carboxylic acid
• 英文别名: 1-(4-Hydroxy-phenyl)-5-oxo-pyrrolidin-3-carbonsaeure；(RS)-1-(4-hydroxyphenyl)-5-oxo-pyrrolidine-3-carboxylic acid；(R)-1-(4-hydroxyphenyl)-5-oxo-pyrrolidine-3-carboxylic acid ester；1-(4-Hydroxyphenyl)-5-oxo-3-pyrrolidinecarboxylic acid；(RS)-1-(4-hydroxyoxy-phenyl)-5-oxo-pyrrolidme-3-carboxylic acid
• CAS: 39629-88-4
• 化学式: C₁₁H₁₁NO₄
• mdl: MFCD01422913
• 分子量: 221.213
• InChiKey: BJEYOPOUMSTVNI-UHFFFAOYSA-N

物化性质

• 熔点：
  201-202 °C
• 沸点：
  601.8±50.0 °C(Predicted)
• 密度：
  1.463±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 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：
  77.8
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 海关编码：
  2933790090
• 储存条件：
  存储条件：2-8°C，密封保存，并保持干燥。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 1-(4-Hydroxyphenyl)-5-oxopyrrolidine-3-carboxylic acid
Synonyms: 1-(4-Hydroxyphenyl)-2-pyrrolidinone-4-carboxylic acid

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

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Section 3. Composition/information on ingredients.
Ingredient name: 1-(4-Hydroxyphenyl)-5-oxopyrrolidine-3-carboxylic acid
CAS number: 39629-88-4

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

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Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels.
Storage:

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C11H11NO4
Molecular weight: 221.2

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
Non-harzardous for air and ground transportation.

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  1-(4-羟基-苯基)-5-氧代-吡咯烷-3-羧酸 在 硫酸 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 methyl 1-(4-ethoxyphenyl)-5-oxo-pyrrolidine-3-carboxylate
  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：

  衣康酸 、 对氨基苯酚 生成 1-(4-羟基-苯基)-5-氧代-吡咯烷-3-羧酸
  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

• 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] PYRROLIDONE DERIVATIVES AS MAOB INHIBITORS<br/>[FR] DERIVES DE PYRROLIDONE TELS QUE DES INHIBITEURS MAOB
  申请人：HOFFMANN LA ROCHE

  公开号：WO2004026825A1

  公开（公告）日：2004-04-01

  Racemic or enantiomerically pure 4-pyrrolidino derivatives of the formula (I), processes for their preparation, pharmaceutical compositions comprising said derivatives, and their use in the prevention and treatment of a disease which is mediated by a monoamine oxidase B inhibitor, in particular Alzheimer's disease and senile dementia.

  光学异构体或对映纯的式(I)的4-吡咯啉衍生物，其制备方法，包含该衍生物的药物组合物，以及其在通过单胺氧化酶B抑制剂介导的疾病的预防和治疗中的用途，特别是阿尔茨海默病和老年性痴呆症。
• Process for the preparation of enantiopure pyrrolidin-2-one derivatives
  申请人：Iding Hans

  公开号：US20050065204A1

  公开（公告）日：2005-03-24

  The present invention relates to a process for the preparation of enantiopure intermediates useful in the synthesis of valuable pharmaceutically active compounds, e.g. MAOB inhibitors, and to novel intermediates of formulae I and II wherein R 21 , R 22 , R 23 and R 24 are as defined in the description and claims.

  本发明涉及一种用于制备对合成有价值的药用活性化合物，例如MAOB抑制剂的手性纯中间体的过程，并涉及式I和II的新型中间体，其中R21、R22、R23和R24如描述和权利要求中所定义。
• 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。
• 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