methyl 2-(4-hydroxy-2-methoxyphenoxy)acetate

• 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: methyl 2-(4-hydroxy-2-methoxyphenoxy)acetate
• 英文别名: Methyl 2-(4-hydroxy-2-methoxyphenoxy)acetate
• 化学式: C₁₀H₁₂O₅
• 分子量: 212.202
• InChiKey: UCQYFZNCKNAUDP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 2-(4-hydroxy-2-methoxyphenoxy)acetate 在 盐酸 、 amalgamated zinc 作用下， 以 甲醇 为溶剂， 反应 8.5h， 生成 methyl 2-(5-ethyl-4-hydroxy-2-methoxyphenoxy)acetate
  参考文献：
  名称：

  基于贝特酸酯的酰基和烷基苯氧基乙酸甲酯和1,2-二氢喹啉的合成及生物活性

  摘要：

  我们的小组最近报道了由基于纤维状结构的一系列高效降血脂药，其合成从异香草醛衍生物开始。为了评估基于香草醛的异构体对它们的降血脂活性的生物立体效应，本研究着重于5-酰基-1-苯氧基乙酸甲酯5a - c及其饱和侧链5-烷基-1的合成-苯氧乙酸酯6a – c。它们强大的体内作用与抑制HMG-CoA还原酶有关。由于1,2-二氢喹啉可抑制该酶，因此一系列此类杂环（9a – d）是通过我们有效的区域选择性，一步一步，无溶剂的方法制备的。除了在体内表现出降血脂活性外，某些化合物在体外还表现出抗真菌，抗氧化剂和细胞毒活性。通过对接模拟检查了四种化合物在HMGRh活性位点的结合模式，观察到与辛伐他汀靶向的大多数氨基酸发生相互作用。

  DOI：

  10.1007/s00044-019-02496-1
• 作为产物：
  描述：

  邻甲氧基苯乙酸酯 在 aluminum (III) chloride 、 水 、 sodium methylate 、 potassium carbonate 、 对甲苯磺酸 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 68.0h， 生成 methyl 2-(4-hydroxy-2-methoxyphenoxy)acetate
  参考文献：
  名称：

  Synthesis and biological evaluation of phenoxyacetic acid derivatives as novel free fatty acid receptor 1 agonists

  摘要：

  Free fatty acid receptor 1 (FFA1) is a new potential drug target for the treatment of type 2 diabetes because of its role in amplifying glucose-stimulated insulin secretion in pancreatic β-cell. In the present studies, we identified phenoxyacetic acid derivative (18b) as a potent FFA1 agonist (EC50=62.3 nM) based on the structure of phenylpropanoic acid derivative 4p. Moreover, compound 18b could significantly improve oral glucose tolerance in ICR mice and dose-dependently reduced glucose levels in type 2 diabetic C57BL/6 mice without observation of hypoglycemic side effect. Additionally, compound 18b exhibited acceptable PK profiles. In summary, compound 18b with ideal PK profiles exhibited good activity in vitro and in vivo, and might be a promising drug candidate for the treatment of diabetes mellitus.

  DOI：

  10.1016/j.bmc.2014.11.016

文献信息

• Synthesis and biological activity of fibrate-based acyl- and alkyl-phenoxyacetic methyl esters and 1,2-dihydroquinolines
  作者：Abraham Pucheta、Aarón Mendieta、Damián A. Madrigal、Roberto I. Hernández-Benitez、Liseth Romero、Leticia Garduño-Siciliano、Catalina Rugerio-Escalona、María C. Cruz-López、Fabiola Jiménez、Alejandra Ramírez-Villalva、Aydeé Fuentes-Benites、Carlos González-Romero、Omar Gómez-García、Julio López、Miguel A. Vázquez、Blanca Rosales-Acosta、Lourdes Villa-Tanaca、Alfonso Sequeda-Juárez、Eva Ramón-Gallegos、Germán Chamorro-Cevallos、Francisco Delgado、Joaquín Tamariz

  DOI：10.1007/s00044-019-02496-1

  日期：2020.3

  constituted by a fibrate-based structure was recently reported by our group, whose synthesis started from isovanillin derivatives. In the interest of evaluating the bioisosteric effect of the vanillin-based isomers on their antihyperlipidemic activity, the present study focuses on the synthesis of 5-acyl-1-phenoxyacetic methyl esters 5a–c and their saturated side-chain 5-alkyl-1-phenoxyacetates 6a–c. Their

  我们的小组最近报道了由基于纤维状结构的一系列高效降血脂药，其合成从异香草醛衍生物开始。为了评估基于香草醛的异构体对它们的降血脂活性的生物立体效应，本研究着重于5-酰基-1-苯氧基乙酸甲酯5a - c及其饱和侧链5-烷基-1的合成-苯氧乙酸酯6a – c。它们强大的体内作用与抑制HMG-CoA还原酶有关。由于1,2-二氢喹啉可抑制该酶，因此一系列此类杂环（9a – d）是通过我们有效的区域选择性，一步一步，无溶剂的方法制备的。除了在体内表现出降血脂活性外，某些化合物在体外还表现出抗真菌，抗氧化剂和细胞毒活性。通过对接模拟检查了四种化合物在HMGRh活性位点的结合模式，观察到与辛伐他汀靶向的大多数氨基酸发生相互作用。
• Synthesis and biological evaluation of phenoxyacetic acid derivatives as novel free fatty acid receptor 1 agonists
  作者：Xuekun Wang、Tianxiao Zhao、Baowei Yang、Zheng Li、Jian Cui、Yuxuan Dai、Qianqian Qiu、Hao Qiang、Wenlong Huang、Hai Qian

  DOI：10.1016/j.bmc.2014.11.016

  日期：2015.1

  Free fatty acid receptor 1 (FFA1) is a new potential drug target for the treatment of type 2 diabetes because of its role in amplifying glucose-stimulated insulin secretion in pancreatic β-cell. In the present studies, we identified phenoxyacetic acid derivative (18b) as a potent FFA1 agonist (EC50=62.3 nM) based on the structure of phenylpropanoic acid derivative 4p. Moreover, compound 18b could significantly improve oral glucose tolerance in ICR mice and dose-dependently reduced glucose levels in type 2 diabetic C57BL/6 mice without observation of hypoglycemic side effect. Additionally, compound 18b exhibited acceptable PK profiles. In summary, compound 18b with ideal PK profiles exhibited good activity in vitro and in vivo, and might be a promising drug candidate for the treatment of diabetes mellitus.