2-(2,6-二甲基苯氧基)丙酸乙酯 | 124317-26-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-(2,6-二甲基苯氧基)丙酸乙酯
• 英文名称: (RS)-ethyl 2-(2,6-dimethylphenoxy)propanoate
• 英文别名: Aethyl-2-(2,6-dimethylphenoxy)propionat；Ethyl 2-(2,6-dimethylphenoxy)propanoate
• CAS: 124317-26-6
• 化学式: C₁₃H₁₈O₃
• 分子量: 222.284
• InChiKey: SADXEKYGWAIJCX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 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：

  2-(2,6-二甲基苯氧基)丙酸乙酯 在 palladium on activated charcoal 盐酸 、 氯化亚砜 、 乙醇 、 硫酸 、 氢气 、 硝酸 作用下， 以 乙醇 为溶剂， 反应 2.17h， 生成 2-(4,6-Dimethyl-3H-benzoimidazol-5-yloxy)-propionic acid ethyl ester
  参考文献：
  名称：

  Potential antisecretory antidiarrheals. 2. .alpha.2-Adrenergic 2-[(aryloxy)alkyl]imidazolines

  摘要：

  Lofexidine, an alpha 2-agonist, has central hypotensive activity and peripheral intestinal antisecretory activity. Analogues were synthesized with increased polarity in an attempt to prevent penetration of the blood-brain barrier. The compounds were evaluated in the cholera toxin treated ligated jejunum of the rat and in the Ussing chamber with a rabbit ileum preparation. Active compounds were determined to be alpha 2-adrenergic agonists by yohimbine reversals of their Ussing chamber activities. The 2,6-dimethyl derivative of lofexidine, 4a, was as active as lofexidine in vivo, but derivatives with 2,6-substituents larger than ethyl were inactive. (Aryloxy)alkyl derivatives which have an imidazoline and a methyl or larger group as part of the alkyl exhibited the best antisecretory activity. Compounds with substituents in the para position of the phenyl ring were generally inactive. 3-Amino-2,6-dimethyl derivative 21 was twice as active as 4a. A 2-methyl substituent is required in the 3-amino series to retain good activity. 2-Methyl derivative 12a had activity comparable to that of 4a, while 6-methyl derivative 12f was inactive. Substituents on the 3-amino group did not affect the activity, but substituting a hydroxyl for the amino group produced an inactive compound. Replacing the phenyl moiety with a 4-indole resulted in retention of activity, but other heterocycles were inactive. Compound 12a was resolved and d isomer 32 was five times more potent than l isomer 33. The more active compounds in the rat cholera toxin assay (RCTA), when evaluated in the dog, exhibited antisecretory activity but also exhibited central nervous system (CNS) effects, sedation and ataxia, at 10 mg/kg, and in spontaneously hypertensive rats at 50 mg/kg. A measure of polarity, log P, was calculated for the (aryloxy)alkyl groups. Regression analysis showed no correlation of antisecretory ED50 to the calculated log P. The active compounds did not show a separation of the central CNS effects from the peripheral antisecretory activity by increasing the polarity.

  DOI：

  10.1021/jm00164a024
• 作为产物：
  描述：

  2,6-二甲基苯酚 、 2-溴丙酸乙酯 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 5.5h， 以85%的产率得到2-(2,6-二甲基苯氧基)丙酸乙酯
  参考文献：
  名称：

  粪肠球菌胸苷酸合酶与叶酸结合位点抑制剂的X射线晶体结构

  摘要：

  如今，由粪肠球菌（Ef）引起的感染代表了一个相关的健康问题。我们从该生物中选择了胸苷酸合酶（TS）作为抗菌治疗的潜在特定靶标。我们先前已经证明，尽管细菌TS和人类TS之间具有较高的结构相似性，但仍可以实现蛋白质的物种特异性抑制。我们之前已经获得了Ef与代谢物5-甲酰基-四氢叶酸（5-FTHF）形成复合物时，蛋白质的TS晶体结构表明该蛋白质作为代谢物储库的作用；但是，蛋白质抑制剂复合物仍然缺失。在目前的工作中，我们从我们的内部库中鉴定了一些带有邻苯二甲酰亚胺核心的抑制剂，并对Ef TS进行了结晶学筛选。我们获得了两个X射线晶体学结构：第一个X射线晶体结构：第一个亚基结合了弱邻苯二甲酰亚胺抑制剂，另一个亚基结合了5-羟基亚甲基-6-氢叶酸（5-HMHF）。第二个与甲氨蝶呤复合的X射线结构。获得的结构信息证实了Ef TS作为叶酸池系统中所涉及的酶的作用，并为基于结构的药物设计提供了结构基础。

  DOI：

  10.1016/j.ejmech.2016.07.066

文献信息

• GB919126
  申请人：——

  公开号：——

  公开（公告）日：——
• 2‘,6‘-Dimethylphenoxyacetyl:  A New Achiral High Affinity P₃-P₂ Ligand for Peptidomimetic-Based HIV Protease Inhibitors
  作者：Pierre L. Beaulieu、Paul C. Anderson、Dale R. Cameron、Gilbert Croteau、Vida Gorys、Chantal Grand-Maître、Daniel Lamarre、Francine Liard、William Paris、Louis Plamondon、François Soucy、Diane Thibeault、Dominik Wernic、Christiane Yoakim、Susan Pav、Liang Tong

  DOI：10.1021/jm990336n

  日期：2000.3.1

  Starting from palinavir (1), our lead HIV protease inhibitor, we have discovered a new series of truncated analogues in which the P-3-P-2 quinaldic-valine portion of 1 was replaced by 2',6'-dimethylphenoxyacetyl. With EC50's in the 1-2 nM range, some of these compounds are among the most potent inhibitors of HIV replication in vitro, reported to date. One of the most promising members in this series (compound 27, BILA 2185 BS) exhibited a favorable overall pharmacokinetic profile, with 61% apparent oral bioavailability in rat. X-ray crystal structures and molecular modeling were used to rationalize the high potency resulting from incorporation of this structurally simple, achiral ligand into the P-3-P-2 position of hydroxyethylamine-based HIV protease inhibitors.
• Azzolina; Collina; Ghislandi, Il Farmaco, 1993, vol. 48, # 10, p. 1401 - 1416
  作者：Azzolina、Collina、Ghislandi

  DOI：——

  日期：——
• Azzolina; Ghislandi, Il Farmaco, 1993, vol. 48, # 6, p. 713 - 724
  作者：Azzolina、Ghislandi

  DOI：——

  日期：——
• X-ray crystal structures of Enterococcus faecalis thymidylate synthase with folate binding site inhibitors
  作者：Alessia Catalano、Rosaria Luciani、Alessia Carocci、Debora Cortesi、Cecilia Pozzi、Chiara Borsari、Stefania Ferrari、Stefano Mangani

  DOI：10.1016/j.ejmech.2016.07.066

  日期：2016.11

  crystallographic screening towards EfTS. We obtained two X-ray crystallographic structures: the first with a weak phthalimidic inhibitor bound in one subunit and 5-hydroxymethylene-6-hydrofolic acid (5-HMHF) in the other subunit; a second X-ray structure complex with methotrexate. The structural information achieved confirm the role of EfTS as an enzyme involved in the folate pool system and provide a structural

  如今，由粪肠球菌（Ef）引起的感染代表了一个相关的健康问题。我们从该生物中选择了胸苷酸合酶（TS）作为抗菌治疗的潜在特定靶标。我们先前已经证明，尽管细菌TS和人类TS之间具有较高的结构相似性，但仍可以实现蛋白质的物种特异性抑制。我们之前已经获得了Ef与代谢物5-甲酰基-四氢叶酸（5-FTHF）形成复合物时，蛋白质的TS晶体结构表明该蛋白质作为代谢物储库的作用；但是，蛋白质抑制剂复合物仍然缺失。在目前的工作中，我们从我们的内部库中鉴定了一些带有邻苯二甲酰亚胺核心的抑制剂，并对Ef TS进行了结晶学筛选。我们获得了两个X射线晶体学结构：第一个X射线晶体结构：第一个亚基结合了弱邻苯二甲酰亚胺抑制剂，另一个亚基结合了5-羟基亚甲基-6-氢叶酸（5-HMHF）。第二个与甲氨蝶呤复合的X射线结构。获得的结构信息证实了Ef TS作为叶酸池系统中所涉及的酶的作用，并为基于结构的药物设计提供了结构基础。