5-(3-甲氧基-苯基)-异噁唑-3-羧酸 | 668971-56-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 5-(3-甲氧基-苯基)-异噁唑-3-羧酸
• 中文别名: 5-(3-甲氧苯基)异恶唑-3-羧酸；5-(3-甲氧苯基)-3-异恶唑甲酸；5-(3-甲氧基-苯基)-异恶唑-3-羧酸；5-(3-甲氧苯基)-1,2-恶唑-3-羧酸
• 英文名称: 5-(3-methoxyphenyl)isoxazole-3-carboxylic acid
• 英文别名: 5-(3-methoxyphenyl)-1,2-oxazole-3-carboxylic acid
• CAS: 668971-56-0
• 化学式: C₁₁H₉NO₄
• mdl: MFCD05238071
• 分子量: 219.197
• InChiKey: MQNOGHHJKQIZKN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  72.6
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  3-氨甲基吡啶 、 5-(3-甲氧基-苯基)-异噁唑-3-羧酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙腈 为溶剂， 反应 24.5h， 生成 5-(3-Methoxyphenyl)-N-[(pyridin-3-YL)methyl]-1,2-oxazole-3-carboxamide
  参考文献：
  名称：

  Novel N-benzylpyridinium moiety linked to arylisoxazole derivatives as selective butyrylcholinesterase inhibitors: Synthesis, biological evaluation, and docking study

  摘要：

  A novel series of N-benzylpyridinium moiety linked to arylisoxazole ring were designed, synthesized, and evaluated for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. Synthesized compounds were classified into two series of 5a-i and 5j-q considering the position of positively charged nitrogen of pyridinium moiety (3- or 4- position, respectively) connected to isoxazole carboxamide group. Among the synthesized compounds, compound 5n from the second series of compounds possessing 2,4-dichloroaryl group connected to isoxazole ring was found to be the most potent AChE inhibitor (IC50 = 5.96 mu M) and compound 5j also from the same series of compounds containing phenyl group connected to isoxazole ring demonstrated the most promising inhibitory activity against BChE (IC50, = 0.32 mu M). Also, kinetic study demonstrated competitive inhibition mode for both AChE and BChE inhibitory activity. Docking study was also performed for those compounds and desired interactions with those active site amino acid residues were confirmed through hydrogen bonding as well as pi-pi and pi-anion interactions. In addition, the most potent compounds were tested against BACE1 and their neuroprotectivity on A beta-treated neurotoxicity in PC12 cells which depicted negligible activity. It should be noted that most of the synthesized compounds from both categories 5a-i and 5j-q showed a significant selectivity toward BChE. However, series 5j-q were more active toward AChE than series 5a-i.

  DOI：

  10.1016/j.bioorg.2019.103192
• 作为产物：
  描述：

  3-甲氧基苯乙酮 在 盐酸羟胺 、 sodium ethanolate 、 potassium hydroxide 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 21.0h， 生成 5-(3-甲氧基-苯基)-异噁唑-3-羧酸
  参考文献：
  名称：

  作为 α-葡萄糖苷酶抑制剂的新型 5-芳基异恶唑-1,3,4-噻二唑杂化物的设计和合成

  摘要：

  背景：α-葡萄糖苷酶抑制剂在 2 型糖尿病的治疗中占有重要地位。在这方面，迫切需要开发新型高效的非糖基抑制剂。 目的：设计合成具有α-葡萄糖苷酶抑制活性的新型5-芳基异恶唑-1,3,4-噻二唑杂化物。 方法：通过各种5-芳基异恶唑-3-羧酸与2-((5-氨基-1,3,4-噻二唑-2-基)硫代)乙酸乙酯反应合成了不同的衍生物。最后，评估了它们的 α-葡萄糖苷酶抑制活性。 结果：发现 2-((5-(5-(2-氯苯基)isoxazole-3-carboxamido)-1,3,4-thidiazol-2-yl)thio) 乙酸乙酯 (5j) 是最有效的化合物 (IC 50 = 180.1 μM) 与作为参考药物的阿卡波糖 (IC 50 = 750.0 μM) 相比。此外，5j 的动力学研究揭示了竞争性抑制和对接研究结果表明该化合物与位于 α-葡萄糖苷酶活性位点附近的氨基酸残基之间存在所需的相互作用。

  DOI：

  10.2174/1570180817999201104125018

文献信息

• [EN] SMALL MOLECULE INHIBITORS OF THE MITOCHONDRIAL PERMEABILITY TRANSITION PORE (mtPTP)<br/>[FR] PETITES MOLÉCULES INHIBITRICES DU PORE DE TRANSITION DE PERMÉABILITÉ MITOCHONDRIALE (MTPTP)
  申请人：UNIV KANSAS

  公开号：WO2016073633A1

  公开（公告）日：2016-05-12

  The present technology relates to compounds of any one of Formula I, II, IIa, III, IV, and/or V as described herein and their tautomers and/or pharmaceutically acceptable salts, compositions, and methods of uses thereof.

  目前的技术涉及到本文描述的任一式I、II、IIa、III、IV和/或V的化合物，以及它们的互变异构体和/或药用盐、组合物以及使用方法。
• [EN] ANTIBACTERIAL BENZOIC ACID DERIVATIVES<br/>[FR] DERIVES D'ACIDES BENZOIQUES ANTIBACTERIENS
  申请人：UPJOHN CO

  公开号：WO2004018428A1

  公开（公告）日：2004-03-04

  The invention provides antimicrobial agents and methods of using the agents for sterilization, sanitation, antisepsis, disinfection, and treatment of infections in mammals.

  这项发明提供了抗菌剂和使用这些剂进行哺乳动物的消毒、卫生、防腐、消毒和治疗感染的方法。
• Discovery, Synthesis, and Optimization of Diarylisoxazole-3-carboxamides as Potent Inhibitors of the Mitochondrial Permeability Transition Pore
  作者：Sudeshna Roy、Justina Šileikytė、Marco Schiavone、Benjamin Neuenswander、Francesco Argenton、Jeffrey Aubé、Michael P. Hedrick、Thomas D. Y. Chung、Michael A. Forte、Paolo Bernardi、Frank J. Schoenen

  DOI：10.1002/cmdc.201500284

  日期：2015.10

  activity against mitochondrial swelling (EC50<0.39 μM) and showed no interference on the inner mitochondrial membrane potential (rhodamine 123 uptake EC50>100 μM). This enabled the construction of a series of picomolar mtPTP inhibitors that also potently increase the calcium retention capacity of the mitochondria. Finally, the therapeutic potential and in vivo efficacy of one of the most potent analogues

  线粒体通透性转换孔（mtPTP）是一种需要Ca 2+的巨型通道，在病理条件下会导致Ca 2+释放失调和线粒体功能障碍，最终导致细胞死亡。尽管 mtPTP 是许多人类病理的潜在治疗靶点，但其作为药物靶点的潜力目前尚未实现。在这里，我们描述了围绕命中1、5- (3-羟基苯基) -N- (3,4,5-三甲氧基苯基)异恶唑-3-甲酰胺发起的优化工作，发现其对线粒体肿胀具有良好的抑制活性 (EC 50 < 0.39微米) 并显示对线粒体内膜电位没有干扰（罗丹明 123 摄取 EC 50 >100 μ M）。这使得构建一系列皮摩尔 mtPTP 抑制剂成为可能，这些抑制剂也有效地增加了线粒体的钙保留能力。最后，最有效的类似物之一N- (3-氯-2-甲基苯基)-5-(4-氟-3-羟基苯基)异恶唑-3-甲酰胺 ( 60 )的治疗潜力和体内功效是在 VI 型胶原蛋白先天性肌营养不良的生物学相关斑马鱼模型中得到验证。
• Design and Synthesis of Novel Arylisoxazole‐Chromenone Carboxamides: Investigation of Biological Activities Associated with Alzheimer's Disease
  作者：Mina Saeedi、Arezoo Rastegari、Roshanak Hariri、Seyedeh Sara Mirfazli、Mohammad Mahdavi、Najmeh Edraki、Omidreza Firuzi、Tahmineh Akbarzadeh

  DOI：10.1002/cbdv.201900746

  日期：2020.5

  progress of Alzheimer's disease. It could inhibit BACE1 by 48.46 % at 50 μm. It also showed 6.4 % protection at 25 μm and satisfactory chelating ability toward Zn2+, Fe2+, and Cu2+ ions. Docking studies of 5‐(3‐nitrophenyl)‐N‐4‐[(2‐oxo‐2H‐1‐benzopyran‐7‐yl)oxy]phenyl}‐1,2‐oxazole‐3‐carboxamide and 5‐(3‐chlorophenyl)‐N‐4‐[(2‐oxo‐2H‐1‐benzopyran‐7‐yl)oxy]phenyl}‐1,2‐oxazole‐3‐carboxamide confirmed desired

  基于改进的 Ellman 方法，设计、合成了一系列新的杂化芳基异恶唑-色烯酮甲酰胺，并评估了它们的胆碱酯酶 (ChE) 抑制活性。在合成的化合物中，5-(3-硝基苯基)-N-4-[(2-oxo-2H-1-benzopyran-7-yl)oxy]phenyl}-1,2-oxazole-3-carboxamide 描述的最多乙酰胆碱酯酶 (AChE) 抑制活性 (IC50=1.23 μm) 和 5-(3-chlorophenyl)-N-4-[(2-oxo-2H-1-benzopyran-7-yl)oxy]phenyl}-1,2发现 -oxazole-3-carboxamide 是最有效的丁酰胆碱酯酶 (BChE) 抑制剂 (IC50=9.71 μm)。进一步研究了 5-(3-Nitrophenyl)-N-4-[(2-oxo-2H-1-benzopyran-7-yl)oxy]phenyl}-1
• Novel <i>N</i> ‐benzylpiperidine derivatives of 5‐arylisoxazole‐3‐carboxamides as anti‐Alzheimer's agents
  作者：Mina Saeedi、Peyman Felegari、Aida Iraji、Roshanak Hariri、Arezoo Rastegari、S. Sara Mirfazli、Najmeh Edraki、Omidreza Firuzi、Mohammad Mahdavi、Tahmineh Akbarzadeh

  DOI：10.1002/ardp.202000258

  日期：2021.3

  The complex pathophysiology of Alzheimer's disease (AD) has prompted researchers to develop multitarget-directed molecules to find an effective therapy against the disease. In this context, a novel series of N-(1-benzylpiperidin-4-yl)-5-arylisoxazole-3-carboxamide derivatives were designed, synthesized, and evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). In vitro biological

  阿尔茨海默病 (AD) 的复杂病理生理学促使研究人员开发多靶点定向分子，以寻找针对该疾病的有效疗法。在这种情况下，设计、合成了一系列新的 N-(1-benzylpiperidin-4-yl)-5-arylisoxazole-3-carboxamide 衍生物，并针对乙酰胆碱酯酶 (AChE) 和丁酰胆碱酯酶 (BuChE) 进行了评估。体外生物学评估表明，化合物 4e 是最好的 AChE（IC50 = 16.07 μM）和 BuChE 抑制剂（IC50 = 15.16 μM）。还进行了 4e 的动力学研究，这表明对两种酶都有混合型抑制作用。分子对接研究表明，化合物 4e 与 AChE 和 BuChE 的活性位点非常吻合，与 AChE 中的关键残基 Glu199、Trp84、Asp72、Tyr121 和 Phe288 以及 His438、Trp82、BuChE 中的 Ala328、Tyr332、Phe329、Thr120