methyl 2-phenoxybutanoate | 143094-66-0

• 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-phenoxybutanoate
• 英文别名: Methyl 2-phenoxybutyrate
• CAS: 143094-66-0
• 化学式: C₁₁H₁₄O₃
• mdl: MFCD23713174
• 分子量: 194.23
• InChiKey: MFMSDSMLLUAITD-UHFFFAOYSA-N

物化性质

• 保留指数：
  1334

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 2-phenoxybutanoate 在 aluminum (III) chloride 、 水 、 sodium methylate 、 potassium carbonate 、 对甲苯磺酸 、 间氯过氧苯甲酸 、 potassium iodide 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 28.0h， 生成 2-(4-((2′,6′-dimethyl-4′-(3-(methylsulfonyl)propoxy)[1,1′-biphenyl]-3-yl)methoxy)phenoxy)butanoic acid
  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
• 作为产物：
  描述：

  methyl 2-chlorobutanoate 、 苯酚 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 methyl 2-phenoxybutanoate
  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

• Enzymatic enantioselective ester hydrolysis by carboxylesterase NP
  作者：J. W. H. Smeets、A. P. G. Kieboom

  DOI：10.1002/recl.19921111104

  日期：——

  and N-arylalanine esters. The propionate esters yielded propionic acids as (S) enantiomers, whereas the alanine esters yielded the (R) enantiomers. Without a 2-aryl substituent, the enzymatic hydrolysis of the propionates occurred at a lower rate without acceptable enantioselectivity. In addition to 2-substituted propionates, only a few other esters were hydrolyzed with high enantioselectivity by carboxylesterase

  为了确定该酶的范围和局限性，已经研究了通过羧酸酯酶NP对一系列羧酸酯的酶促水解。当芳族部分是2-取代基的一部分时，以高对映选择性水解2-取代的丙酸酯。对映选择性水解可以用几种2-芳基丙酸酯，2-（芳氧基）丙酸酯和N-芳基丙氨酸酯完成。丙酸酯产生丙酸为（S）对映异构体，而丙氨酸酯产生（R）对映体。没有2-芳基取代基，丙酸酯的酶水解以较低的速率发生，而没有可接受的对映选择性。除2-取代的丙酸酯外，只有少数其他酯被羧酸酯酶NP水解而具有高对映选择性，例如一些前手性二取代丙二酸酯。1-苯基乙基乙酸酯是在酯的醇部分中具有手性的唯一底物，发现其被对映选择性地水解。
• Chlorine substituents and linker topology as factors of 5-HT6R activity for novel highly active 1,3,5-triazine derivatives with procognitive properties in vivo
  作者：Sylwia Sudoł、Katarzyna Kucwaj-Brysz、Rafał Kurczab、Natalia Wilczyńska、Magdalena Jastrzębska-Więsek、Grzegorz Satała、Gniewomir Latacz、Monika Głuch-Lutwin、Barbara Mordyl、Ewa Żesławska、Wojciech Nitek、Anna Partyka、Kamila Buzun、Agata Doroz-Płonka、Anna Wesołowska、Anna Bielawska、Jadwiga Handzlik

  DOI：10.1016/j.ejmech.2020.112529

  日期：2020.10

  promising tool for future treatment of memory impairment. Hence, this study has supplied highly potent 5-HT6R agents with procognitive effects, which represent an original chemical class of 1,3,5-triazines, different from widely studied sulfone and indole-like 5-HT6R ligands. The new compounds were rationally designed as modifications of lead, 4-(1-(2-chlorophenoxy)ethyl)-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine

  根据最近的证据，5-HT 6 R配体是未来治疗记忆障碍的有前途的工具。因此，本研究提供了具有认知作用的强效5-HT 6 R药物，它代表了1,3,5-三嗪的原始化学类别，与广泛研究的砜和吲哚样5-HT 6 R配体不同。新化合物经过合理设计，是对铅4-（1-（2-氯苯氧基）乙基）-6-（4-甲基哌嗪-1-基）-1,3,5-三嗪-2-胺的修饰（1） ，涉及引入：（i）苯环上的两个氯和（ii）将三嗪环连接到芳族醚上的各种连接基。合成，体外和对19种新化合物进行了体内生物学测试和计算机辅助SAR分析。相对于5-HT 2A R，5-HT 7 R和D 2 R，大多数新的三嗪类 化合物对5-HT 6 R表现出高亲和力（K i <100 nM）和选择性。晶体学支持的对接研究包括量子极化的配体对接（QPLD），表明氯原子可能参与不同类型的卤素键，但是，连接子的性质似乎主要影响5-HT 6 R的亲和力。4- [1-（2
• Preparation method for chlorophenoxycarboxylate
  申请人：SHANDONG RAINBOW BIOTECH CO., LTD.

  公开号：US11078150B2

  公开（公告）日：2021-08-03

  Provided is a method for producing a chlorophenoxycarboxylate, comprising the following steps of: a phenoxycarboxylate under actions of a catalyst A and a catalyst B performing a selective chlorination of a chlorinating agent at a 2-position and/or a 4-position to obtain the chlorophenoxycarboxylate; the catalyst A is a Lewis acid; and the catalyst B has the following structure: R1′—S—R2′. The present disclosure redesigns the process route, and finely screens the catalyst and the chlorinating agent, thereby effectively improving the chlorination selectivity while avoiding the loss of the active ingredient, and the content of the obtained chlorophenoxycarboxylate can reach more than 98.5%, and the yield can reach more than 99%.

  本发明提供了一种生产氯苯氧羧酸酯的方法，包括以下步骤：苯氧羧酸酯在催化剂 A 和催化剂 B 的作用下，在 2 位和/或 4 位上对氯化剂进行选择性氯化，以获得氯苯氧羧酸酯；催化剂 A 是路易斯酸；催化剂 B 具有以下结构：R1′-S-R2′。本发明重新设计了工艺路线，对催化剂和氯化剂进行了精细筛选，从而在避免有效成分损失的同时，有效提高了氯化选择性，得到的氯苯氧羧酸酯含量可达98.5%以上，收率可达99%以上。
• Irimie, Florin-Dan; Mager, Sorin; Brown, Eric, Revue Roumaine de Chimie, 1995, vol. 40, # 4, p. 369 - 376
  作者：Irimie, Florin-Dan、Mager, Sorin、Brown, Eric、Horn, Mihai

  DOI：——

  日期：——
• Preparation of nitroarylacetic acid esters and derivatives thereof
  申请人：ETHYL CORPORATION

  公开号：EP0077662B1

  公开（公告）日：1985-10-02