2-(carboxymethoxy)-3-methylbenzoic acid | 60770-15-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(carboxymethoxy)-3-methylbenzoic acid
• CAS: 60770-15-2
• 化学式: C₁₀H₁₀O₅
• 分子量: 210.186
• InChiKey: YLKRPDWSFJVQTL-UHFFFAOYSA-N

物化性质

• 熔点：
  207 °C(Solv: methanol (67-56-1))
• 沸点：
  409.5±30.0 °C(Predicted)
• 密度：
  1.370±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  83.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(carboxymethoxy)-3-methylbenzoic acid 在 N-甲基吗啉 、 ammonium hydroxide 、 potassium permanganate 、 ammonium acetate 、 水 、 sodium acetate 、 乙酸酐 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 16.0h， 生成 (Z)-2-(3,4-dihydroxybenzylidene)-3-oxo-2,3-dihydrobenzofuran-7-carboxamide
  参考文献：
  名称：

  Discovery and Structure–Activity Relationship of Novel 2,3-Dihydrobenzofuran-7-carboxamide and 2,3-Dihydrobenzofuran-3(2H)-one-7-carboxamide Derivatives as Poly(ADP-ribose)polymerase-1 Inhibitors

  摘要：

  Novel substituted 2,3-dihydrobenzofuran-7-carboxamide (DHBF-7-carboxamide) and 2,3-dihydrobenzofuran-3(2H)-one-7-carboxamide (DHBF-3-one-7-carboxamide) derivatives were synthesized and evaluated as inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1). A structure-based design strategy resulted in lead compound 3 (DHBF-7-carboxamide; IC50 = 9.45 mu M). To facilitate synthetically feasible derivatives, an alternative core was designed, DHBF-3-one-7-carboxamide (36, IC50 = 16.2 mu M). The electrophilic 2-position of this scaffold was accessible for extended modifications. Substituted benzylidene derivatives at the 2-position were found to be the most potent, with 3',4'-dihydroxybenzylidene 58 (IC50 = 0.531 mu M) showing a 30-fold improvement in potency. Various heterocycles attached at the 4'-hydroxyl/4'-amino of the benzylidene moiety resulted in significant improvement in inhibition of PARP-1 activity (e.g., compounds 66-68, 70, 72, and 73; IC50 values from 0.718 to 0.079 mu M). Compound 66 showed selective cytotoxicity in BRCA2-deficient DT40 cells. Crystal structures of three inhibitors (compounds (-)-13c, 59, and 65) bound to a multidomain PARP-1 structure were obtained, providing insights into further development of these inhibitors.

  DOI：

  10.1021/jm5002502
• 作为产物：
  描述：

  3-甲基水杨酸 在 硫酸 、 potassium carbonate 、 potassium hydroxide 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 2-(carboxymethoxy)-3-methylbenzoic acid
  参考文献：
  名称：

  聚（ADP-核糖）聚合酶抑制剂的设计与合成：腺苷口袋结合基序对3-Oxo-2,3-dihydrobenzofuran-7-boxamide的效力和选择性的影响。

  摘要：

  聚腺苷5'-二磷酸核糖）聚合酶（PARP）抑制剂是一类抗癌药物，可阻断PARP蛋白的催化活性。优化我们的先导化合物1（（Z）-2-亚苄基-3-氧代-2,3-二氢苯并呋喃-7-羧酰胺; PARP-1 IC50 = 434 nM）产生了四唑基类似物（51，IC50 = 35 nM）具有更好的抑制作用。用羧基等位取代四唑环（60，IC50 = 68 nM）产生了有希望的新先导，随后对其进行了优化，以获得具有有效PARP-1 IC50值（4-197 nM）的类似物。PARP酶谱分析显示，大多数化合物对PARP-2具有选择性，其IC50值可与临床抑制剂媲美。与PARP-1结合的关键抑制剂的X射线晶体结构说明了与向PARP-1腺苷结合袋延伸的类似附件的相互作用方式。化合物81，一种同工型选择性PARP-1 / -2（IC50 = 30 nM / 2 nM）抑制剂，与同基因BRCA1精制细胞相比，对乳腺

  DOI：

  10.1021/acs.jmedchem.8b01709

文献信息

• [EN] SUBSTITUTED DIHYDROINDENE-4-CARBOXAMIDES AND ANALOGS THEREOF, AND METHODS USING SAME<br/>[FR] DIHYDROINDÈNE-4-CARBOXAMIDES SUBSTITUÉS, LEURS ANALOGUES ET PROCÉDÉS D'UTILISATION CORRESPONDANT
  申请人：ARBUTUS BIOPHARMA CORP

  公开号：WO2018172852A1

  公开（公告）日：2018-09-27

  The present invention includes novel substituted bicyclic compounds, and compositions comprising the same, that can be used to treat or prevent hepatitis B virus (HBV) infections in a patient. In certain embodiments, the compounds and compositions of the invention are capsid inhibitors. (Formula I)

  本发明包括新颖的取代双环化合物，以及包含这些化合物的组合物，可用于治疗或预防患者体内的乙型肝炎病毒（HBV）感染。在某些实施例中，本发明的化合物和组合物是壳蛋白抑制剂。（化学式I）
• 一种作为IRAK抑制剂的化合物
  申请人：上海美悦生物科技发展有限公司

  公开号：CN111560012B

  公开（公告）日：2023-06-23

  本发明涉及适用于治疗癌症和与白细胞介素‑1受体相关激酶(IRAK)相关的炎性疾病的化合物，具体地是一种作为IRAK4抑制剂的化合物及其制备方法和用途，更具体地是式(I)所示的化合物、其立体异构体、消旋体、互变异构体、同位素标记物、氮氧化物或其药学上可接受的盐及其制备方法和用途。本发明中所披露的化合物对IRAK4激酶有良好的抑制作用，并且对其他激酶具有良好的选择性。
• Synthesis, antibacterial activity, and quantitative structure–activity relationships of new (Z)-2-(nitroimidazolylmethylene)-3()-benzofuranone derivatives
  作者：Narges Hadj-esfandiari、Latifeh Navidpour、Hooman Shadnia、Mohsen Amini、Nasrin Samadi、Mohammad Ali Faramarzi、Abbas Shafiee

  DOI：10.1016/j.bmcl.2007.09.062

  日期：2007.11

  A new series of (Z)-2-(1-methyl-5-nitroimidazole-2-ylmethylene)-3(2H)-benzofuranones (11a-p) and (Z)-2-(1-methyl-4-nitroimidazole-5-ylmethylene)-3(2H)-benzofuranones (12a-m) were synthesized and assayed for their antibacterial activity against Gram-positive and Gram-negative bacteria. Most of the 5-nitroimidazole analogues (11a-p) showed a remarkable inhibition of a wide spectrum of Gram-positive bacteria (Staphylococcus aureus, Streptococcus epidermidis, MRSA, and Bacillus subtilis) and Gram-negative Klebsiella pneumoniae, whereas 4-nitroimidazole analogues (12a-m) were not effective against selected bacteria. The quantitative structure-activity relationship investigations were applied to find out the correlation between the experimentally evaluated activities with various parameters of the compounds studied. The QSAR models built in this work had reasonable predictive power and could be explained by the observed trends in activities. (C) 2007 Elsevier Ltd. All rights reserved.
• Meyer,R.; Duczmal, Chemische Berichte, 1913, vol. 46, p. 3378
  作者：Meyer,R.、Duczmal

  DOI：——

  日期：——
• The para-Claisen Rearrangement. I. The Preparation and Rearrangement of the α-and γ-Ethylallyl Ethers of Methyl o-Cresotinate. A Reinvestigation^1,2
  作者：Sara Jane Rhoads、Rebecca Raulins、Rosalie D. Reynolds

  DOI：10.1021/ja01642a026

  日期：1954.7