2-(4-(p-tolylethynyl)phenoxy)acetic acid | 1082058-85-2

• 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-(4-(p-tolylethynyl)phenoxy)acetic acid
• 英文别名: 2-[4-[2-(4-Methylphenyl)ethynyl]phenoxy]acetic acid
• CAS: 1082058-85-2
• 化学式: C₁₇H₁₄O₃
• 分子量: 266.296
• InChiKey: LRDASJQXBWPOLI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(hydroxymethyl)-5-[(4-methoxyphenoxy)methyl]-3-(methylethylidene)-4,5-dihydrofuran-2-one 、 2-(4-(p-tolylethynyl)phenoxy)acetic acid 在 4-二甲氨基吡啶 、 双(2-氧代-3-恶唑烷基)次磷酰氯 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以75%的产率得到(2-[(4-methoxyphenoxy)methyl]-4-(methylethylidene)-5-oxo-2,3-dihydrofuryl)methyl 2-(4-[2-(4-methylphenyl)ethynyl]phenoxy)acetate
  参考文献：
  名称：

  Conformationally Constrained Analogues of Diacylglycerol (DAG). 31. Modulation of the Biological Properties of Diacylgycerol Lactones (DAG-lactones) Containing Rigid-Rod Acyl Groups Separated from the Core Lactone by Spacer Units of Different Lengths

  摘要：

  Diacylglycerol lactones built with a rigid 4-[(methylphenyl)ethynyl]phenyl rod that is separated from the exocyclic acylcarbonyl of the DAG-lactone core by a spacer unit of variable length were synthesized and studied. Binding affinities for a panel of classical and novel PKC isozymes in two different phospholipid environments, one corresponding to the plasma membrane of cells, were determined. The kinetics and site of translocation for the PKC isozymes alpha and delta upon treatment with the compounds were also studied as well as the early response of ERK phosphorylation and the late response of induction of apoptosis in the human prostatic carcinoma cell line LNCaP. Finally, the compounds were evaluated in terms of their interaction with biomimetic lipid/polydiacetylene membranes by the associated chromatic response. The different spatial disposition of the rigid structural motif on the DAG-lactones contributes to differential activity.

  DOI：

  10.1021/jm900186m
• 作为产物：
  描述：

  ethyl 2-(4-(p-tolylethynyl)phenoxy)acetate 在 lithium hydroxide monohydrate 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以63%的产率得到2-(4-(p-tolylethynyl)phenoxy)acetic acid
  参考文献：
  名称：

  Discovery of Potent and Selective Agonists for the Free Fatty Acid Receptor 1 (FFA₁/GPR40), a Potential Target for the Treatment of Type II Diabetes

  摘要：

  A series of 4-phenethynyldihydrocinnamic acid agonists of the free fatty acid receptor 1 (FFA(1)) has been discovered and explored. The preferred compound 20 (TUG-424, EC50 = 32 nM) significantly increased glucose-stimulated insulin secretion at 100 nM and may serve to explore the role of FFA(1) in metabolic diseases such as diabetes or obesity.

  DOI：

  10.1021/jm8010178

文献信息

• [EN] COMPOUNDS FOR THE TREATMENT OF METABOLIC DISEASES<br/>[FR] COMPOSÉS DESTINÉS AU TRAITEMENT DE TROUBLES MÉTABOLIQUES
  申请人：UNIV SYDDANSK

  公开号：WO2010012650A1

  公开（公告）日：2010-02-04

  There is provided novel compounds capable of modulating the G-protein-coupled receptor GPR40, compositions comprising the compounds, and methods for their use for controlling insulin levels in vivo and for the treatment of conditions such as type Il diabetes, hypertension, ketoacidosis, obesity, glucose intolerance, and hypercholesterolemia and related disorders associated with abnormally high or low plasma lipoprotein, triglyceride or glucose levels.

  提供了一种新型化合物，能够调节G蛋白偶联受体GPR40，包括该化合物的组合物和使用方法，用于控制体内胰岛素水平，治疗II型糖尿病、高血压、酮症、肥胖症、葡萄糖不耐受症和与异常高或低血浆脂蛋白、甘油三酯或葡萄糖水平相关的相关疾病。
• COMPOUNDS FOR THE TREATMENT OF METABOLIC DISEASES
  申请人：Ulven Trond

  公开号：US20110152315A1

  公开（公告）日：2011-06-23

  There is provided novel compounds capable of modulating the G-protein-coupled receptor GPR40, compositions comprising the compounds, and methods for their use for controlling insulin levels in vivo and for the treatment of conditions such as type I1 diabetes, hypertension, ketoacidosis, obesity, glucose intolerance, and hypercholesterolemia and related disorders associated with abnormally high or low plasma lipoprotein, triglyceride or glucose levels.

  提供了一种新的化合物，能够调节G蛋白偶联受体GPR40，包括该化合物的组合物以及使用它们的方法，用于控制体内胰岛素水平和治疗诸如2型糖尿病、高血压、酮症酸中毒、肥胖症、葡萄糖耐受性不良以及与异常高或低血浆脂蛋白、甘油三酯或葡萄糖水平有关的相关疾病。
• US8586607B2
  申请人：——

  公开号：US8586607B2

  公开（公告）日：2013-11-19
• Discovery of Potent and Selective Agonists for the Free Fatty Acid Receptor 1 (FFA₁/GPR40), a Potential Target for the Treatment of Type II Diabetes
  作者：Elisabeth Christiansen、Christian Urban、Nicole Merten、Kathrin Liebscher、Kasper K. Karlsen、Alexandra Hamacher、Andreas Spinrath、Andrew D. Bond、Christel Drewke、Susanne Ullrich、Matthias U. Kassack、Evi Kostenis、Trond Ulven

  DOI：10.1021/jm8010178

  日期：2008.11.27

  A series of 4-phenethynyldihydrocinnamic acid agonists of the free fatty acid receptor 1 (FFA(1)) has been discovered and explored. The preferred compound 20 (TUG-424, EC50 = 32 nM) significantly increased glucose-stimulated insulin secretion at 100 nM and may serve to explore the role of FFA(1) in metabolic diseases such as diabetes or obesity.
• Conformationally Constrained Analogues of Diacylglycerol (DAG). 31. Modulation of the Biological Properties of Diacylgycerol Lactones (DAG-lactones) Containing Rigid-Rod Acyl Groups Separated from the Core Lactone by Spacer Units of Different Lengths
  作者：Maria J. Comin、Gabriella Czifra、Noemi Kedei、Andrea Telek、Nancy E. Lewin、Sofiya Kolusheva、Julia F. Velasquez、Ryan Kobylarz、Raz Jelinek、Peter M. Blumberg、Victor E. Marquez

  DOI：10.1021/jm900186m

  日期：2009.5.28

  Diacylglycerol lactones built with a rigid 4-[(methylphenyl)ethynyl]phenyl rod that is separated from the exocyclic acylcarbonyl of the DAG-lactone core by a spacer unit of variable length were synthesized and studied. Binding affinities for a panel of classical and novel PKC isozymes in two different phospholipid environments, one corresponding to the plasma membrane of cells, were determined. The kinetics and site of translocation for the PKC isozymes alpha and delta upon treatment with the compounds were also studied as well as the early response of ERK phosphorylation and the late response of induction of apoptosis in the human prostatic carcinoma cell line LNCaP. Finally, the compounds were evaluated in terms of their interaction with biomimetic lipid/polydiacetylene membranes by the associated chromatic response. The different spatial disposition of the rigid structural motif on the DAG-lactones contributes to differential activity.