(4-phenoxyphenoxy)acetic acid methyl ester | 787575-61-5

• 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: (4-phenoxyphenoxy)acetic acid methyl ester
• 英文别名: methyl 2-(4-phenoxyphenoxy)acetate
• CAS: 787575-61-5
• 化学式: C₁₅H₁₄O₄
• mdl: MFCD10695610
• 分子量: 258.274
• InChiKey: OAJXJMNRDXPXOF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.133
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4-phenoxyphenoxy)acetic acid methyl ester 在 lithium hydroxide monohydrate 作用下， 以 甲醇 、 水 为溶剂， 反应 2.0h， 生成 (4-苯氧基苯氧基)乙酸
  参考文献：
  名称：

  In silico and pharmacological screenings identify novel serine racemase inhibitors

  摘要：

  D-Serine is a coagonist of the N-methyl-D-aspartate (NMDA)-type glutamate receptor and its biosynthesis is catalyzed by serine racemase (SR). The overactivation of the NMDA receptor has been implicated in the development of neurodegenerative diseases, strokes, and epileptic seizures, thus, the inhibitors of SR have potential against these pathological states. Here, we have developed novel inhibitors of SR by in silico screening and in vitro enzyme assay. The newly developed inhibitors have lower IC50 value comparing with that of malonate, one of the standard SR inhibitor. The structural features of novel inhibitors suggest the importance of central amide structure having a phenoxy substituent in their structure for the SR inhibitory activity. The present findings suggest the importance and rational development of new drugs for diseases of NMDAR overactivation.

  DOI：

  10.1016/j.bmcl.2014.07.003
• 作为产物：
  描述：

  4-苯氧基苯酚 、 溴乙酸甲酯 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 生成 (4-phenoxyphenoxy)acetic acid methyl ester
  参考文献：
  名称：

  超越 5-HT6R 药物药效团模型的退出 - 一种获得具有预认知潜力的三嗪衍生物双重 5-HT6/5-HT2A 作用的新策略

  摘要：

  这项研究使我们能够在一组 1,3,5-三嗪化合物中找到第一个高效的 5-HT 6 /5-HT 2A受体（5-HT 6 /5-HT 2A R）双重拮抗剂，因为5-HT 6 R 拮抗剂药效团模型的疏水特征之外的出口。已经进行了具有双环芳族区域的 1,3,5-三嗪的新的含 O 和 S 醚衍生物系列 ( 2 – 16 ) 的设计和合成。在综合药理学筛选中检查了新化合物，包括：放射性配体结合测定、体外功能和 ADMET 研究以及大鼠的行为测试。还分析了晶体学方面和计算机辅助的构效关系。综合方法导致选择化合物12 (4-(4-methylpiperazin-1-yl)-6-(2-(naphthalen-2-ylthio)propan-2-yl)-1,3,5-triazin-2 -胺）具有最显着的双重 5-HT 6 /5-HT 2A R 拮抗作用（5-HT 6 R K i  = 11 nM，5-HT 2A

  DOI：

  10.1016/j.bioorg.2022.105695

文献信息

• SERINE RACEMASE INHIBITOR
  申请人：National University Corporation University of Toyama

  公开号：US20140371291A1

  公开（公告）日：2014-12-18

  A novel serine racemase inhibitor exhibits sufficient activity and specificity. The serine racemase inhibitor includes one or more compounds selected from compounds respectively represented by the following general formulas [MM_1], [DR_1], [DR′_1], [LW_1], and [ED_1] as an active ingredient.

  一种新型的丝氨酸外消旋酶抑制剂表现出足够的活性和特异性。该丝氨酸外消旋酶抑制剂包括一种或多种选自以下通用式[MM_1]、[DR_1]、[DR′_1]、[LW_1]和[ED_1]所代表的化合物的化合物作为活性成分。
• US9216954B2
  申请人：——

  公开号：US9216954B2

  公开（公告）日：2015-12-22
• [EN] SERINE RACEMASE INHIBITOR<br/>[FR] INHIBITEUR DE LA SÉRINE RACÉMASE
  申请人：NAT UNIV CORP UNIV TOYAMA

  公开号：WO2013111798A1

  公开（公告）日：2013-08-01

  【課題】本発明は、十分な活性と特異性のある新規なセリンラセマーゼ阻害剤の提供を目的とする。 【解決手段】下記一般式［ＭＭ＿１］、［ＤＲ＿１］、［ＤＲ'＿１］、［ＬＷ＿１］および［ＥＤ＿１］のいずれかの化合物群から選ばれる１つ以上の化合物を有効成分とするセリンラセマーゼ阻害剤。
• In silico and pharmacological screenings identify novel serine racemase inhibitors
  作者：Hisashi Mori、Ryogo Wada、Jie Li、Tetsuya Ishimoto、Mineyuki Mizuguchi、Takayuki Obita、Hiroaki Gouda、Shuichi Hirono、Naoki Toyooka

  DOI：10.1016/j.bmcl.2014.07.003

  日期：2014.8

  D-Serine is a coagonist of the N-methyl-D-aspartate (NMDA)-type glutamate receptor and its biosynthesis is catalyzed by serine racemase (SR). The overactivation of the NMDA receptor has been implicated in the development of neurodegenerative diseases, strokes, and epileptic seizures, thus, the inhibitors of SR have potential against these pathological states. Here, we have developed novel inhibitors of SR by in silico screening and in vitro enzyme assay. The newly developed inhibitors have lower IC50 value comparing with that of malonate, one of the standard SR inhibitor. The structural features of novel inhibitors suggest the importance of central amide structure having a phenoxy substituent in their structure for the SR inhibitory activity. The present findings suggest the importance and rational development of new drugs for diseases of NMDAR overactivation.
• An exit beyond the pharmacophore model for 5-HT6R agents - a new strategy to gain dual 5-HT6/5-HT2A action for triazine derivatives with procognitive potential
  作者：Katarzyna Kucwaj-Brysz、Wesam Ali、Rafał Kurczab、Sylwia Sudoł-Tałaj、Natalia Wilczyńska-Zawal、Magdalena Jastrzębska-Więsek、Grzegorz Satała、Barbara Mordyl、Ewa Żesławska、Agnieszka-Olejarz-Maciej、Kinga Czarnota、Gniewomir Latacz、Anna Partyka、Anna Wesołowska、Wojciech Nitek、Jadwiga Handzlik

  DOI：10.1016/j.bioorg.2022.105695

  日期：2022.4

  receptor (5-HT6/5-HT2AR) dual antagonists in a group of 1,3,5-triazine compounds as a result of an exit beyond the hydrophobic feature of the pharmacophore model for 5-HT6R antagonists. Design and synthesis of the series (2–16) of new O- and S-containing ether derivatives of 1,3,5-triazines with the double-ring aromatic region have been performed. The new compounds were examined within the comprehensive pharmacological

  这项研究使我们能够在一组 1,3,5-三嗪化合物中找到第一个高效的 5-HT 6 /5-HT 2A受体（5-HT 6 /5-HT 2A R）双重拮抗剂，因为5-HT 6 R 拮抗剂药效团模型的疏水特征之外的出口。已经进行了具有双环芳族区域的 1,3,5-三嗪的新的含 O 和 S 醚衍生物系列 ( 2 – 16 ) 的设计和合成。在综合药理学筛选中检查了新化合物，包括：放射性配体结合测定、体外功能和 ADMET 研究以及大鼠的行为测试。还分析了晶体学方面和计算机辅助的构效关系。综合方法导致选择化合物12 (4-(4-methylpiperazin-1-yl)-6-(2-(naphthalen-2-ylthio)propan-2-yl)-1,3,5-triazin-2 -胺）具有最显着的双重 5-HT 6 /5-HT 2A R 拮抗作用（5-HT 6 R K i  = 11 nM，5-HT 2A