4,5-双-(4-甲氧基-苯基)噻唑-2-羧酸乙酯 | 130717-61-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 4,5-双-(4-甲氧基-苯基)噻唑-2-羧酸乙酯
• 英文名称: 4,5-bis(4-methoxyphenyl)thiazole-2-carboxylic acid ethyl ester
• 英文别名: 2-(ethoxycarbonyl)-4,5-bis(4-methoxyphenyl)thiazole；4,5-bis-(4-methoxy-phenyl)-thiazole-2-carboxylic acid ethyl ester；4,5-bis-(4-methoxy-phenyl)thiazole-2-carboxylic acid ethyl ester；Ethyl 4,5-bis(4-methoxyphenyl)thiazole-2-carboxylate；ethyl 4,5-bis(4-methoxyphenyl)-1,3-thiazole-2-carboxylate
• CAS: 130717-61-2
• 化学式: C₂₀H₁₉NO₄S
• 分子量: 369.441
• InChiKey: DHPDUTGFKMZVBI-UHFFFAOYSA-N

物化性质

• 沸点：
  496.2±55.0 °C(Predicted)
• 密度：
  1.210±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  85.9
• 氢给体数：
  0
• 氢受体数：
  6

安全信息

• 海关编码：
  2934100090

反应信息

• 作为反应物：
  描述：

  4,5-双-(4-甲氧基-苯基)噻唑-2-羧酸乙酯 在 palladium dihydroxide manganese(IV) oxide 、 sodium hydroxide 、 lithium aluminium tetrahydride 、 氢气 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 氯仿 、 乙酸乙酯 为溶剂， 25.0 ℃ 、98.06 kPa 条件下， 反应 14.0h， 生成 3-<4,5-bis(4-methoxyphenyl)thiazol-2-yl>propionic acid
  参考文献：
  名称：

  Antiplatelet Agents Based on Cyclooxygenase Inhibition without Ulcerogenesis. Evaluation and Synthesis of 4,5-Bis(4-methoxyphenyl)-2-substituted-thiazoles

  摘要：

  The syntheses, biological evaluations, and structure-activity relationships of a series of 4,5-bis-( 4-methoxyphenyl)-2-substituted-thiazoles as potent antiplatelet agents with vasodilatory activity are described. 2-Guanidino-4,5-bis(4-methoxyphenyl) thiazole (3), designed from two parent compounds (itazigrel and timegadine), showed inhibitory activity of malondialdehyde (MDA, IC50 = 31 mu M) production which is formed from the cyclooxygenase (CO)-catalyzed oxygenation of arachidonic acid in the synthesis of prostanoids in platelets, with vasodilatory activity (ED(50) 2.0 mu M). Further structure-activity relationship studies on 3 culminated in the preparation of 4,5-bis(4-methoxyphenyl)-2-[(1-methylpiperazin-4-yl)carbonyl] thiazole (10a, FR122047) which exhibited potent inhibitory activity on MDA synthesis in vitro (IC50 = 0.088 mu M) and platelet aggregation in guinea pigs ex vivo (100% inhibition even 6 h after 1.0 mg/kg administration) with vasodilatory activity in vitro (ED(50) = 6.2 mu M). Moreover, 10a demonstrated no ulcerogenesis effect in rats even at 100 mg/kg dosage (safety margin in rats is more than 70 while that of aspirin is only 1.2) in spite of its potent CO inhibition (IC50 = 0.43 mu M(14)), while the use of aspirin, a CO inhibitor and the most popular thromboembolic drug, is restricted by the side effect.(8) Pharmacokinetic studies on 10a have revealed that 10a is detectable in platelet-rich plasma but not in platelet-poor plasma 1 day after oral administration, which indicates that 10a tends to be localized in platelets. This property could be responsible for its low toxicity and reduction of side effects in clinical studies.

  DOI：

  10.1021/jm00034a017
• 作为产物：
  描述：

  茴香偶姻 在 氯化亚砜 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 4,5-双-(4-甲氧基-苯基)噻唑-2-羧酸乙酯
  参考文献：
  名称：

  Antiplatelet Agents Based on Cyclooxygenase Inhibition without Ulcerogenesis. Evaluation and Synthesis of 4,5-Bis(4-methoxyphenyl)-2-substituted-thiazoles

  摘要：

  The syntheses, biological evaluations, and structure-activity relationships of a series of 4,5-bis-( 4-methoxyphenyl)-2-substituted-thiazoles as potent antiplatelet agents with vasodilatory activity are described. 2-Guanidino-4,5-bis(4-methoxyphenyl) thiazole (3), designed from two parent compounds (itazigrel and timegadine), showed inhibitory activity of malondialdehyde (MDA, IC50 = 31 mu M) production which is formed from the cyclooxygenase (CO)-catalyzed oxygenation of arachidonic acid in the synthesis of prostanoids in platelets, with vasodilatory activity (ED(50) 2.0 mu M). Further structure-activity relationship studies on 3 culminated in the preparation of 4,5-bis(4-methoxyphenyl)-2-[(1-methylpiperazin-4-yl)carbonyl] thiazole (10a, FR122047) which exhibited potent inhibitory activity on MDA synthesis in vitro (IC50 = 0.088 mu M) and platelet aggregation in guinea pigs ex vivo (100% inhibition even 6 h after 1.0 mg/kg administration) with vasodilatory activity in vitro (ED(50) = 6.2 mu M). Moreover, 10a demonstrated no ulcerogenesis effect in rats even at 100 mg/kg dosage (safety margin in rats is more than 70 while that of aspirin is only 1.2) in spite of its potent CO inhibition (IC50 = 0.43 mu M(14)), while the use of aspirin, a CO inhibitor and the most popular thromboembolic drug, is restricted by the side effect.(8) Pharmacokinetic studies on 10a have revealed that 10a is detectable in platelet-rich plasma but not in platelet-poor plasma 1 day after oral administration, which indicates that 10a tends to be localized in platelets. This property could be responsible for its low toxicity and reduction of side effects in clinical studies.

  DOI：

  10.1021/jm00034a017

文献信息

• [EN] COMPOUNDS AND COMPOSITIONS AS PPAR MODULATORS<br/>[FR] COMPOSES ET COMPOSITIONS SERVANT DE MODULATEURS PPAR
  申请人：IRM LLC

  公开号：WO2005116000A1

  公开（公告）日：2005-12-08

  The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of the Peroxisome Proliferator-Activated Receptor (PPAR) families, particularly the activity of PPAR.

  这项发明提供了化合物，包括这些化合物的药物组合物，以及使用这些化合物来治疗或预防与过氧化物酶体增殖物激活受体（PPAR）家族的活性相关的疾病或紊乱的方法，特别是PPAR的活性。
• Novel Bisaryl Substituted Thiazoles and Oxazoles as Highly Potent and Selective Peroxisome Proliferator-Activated Receptor δ Agonists
  作者：Robert Epple、Christopher Cow、Yongping Xie、Mihai Azimioara、Ross Russo、Xing Wang、John Wityak、Donald S. Karanewsky、Tove Tuntland、Vân T. B. Nguyêñ-Trân、Cara Cuc Ngo、David Huang、Enrique Saez、Tracy Spalding、Andrea Gerken、Maya Iskandar、H. Martin Seidel、Shin-Shay Tian

  DOI：10.1021/jm9007399

  日期：2010.1.14

  The discovery, synthesis, and optimization of compound 1 from a high-throughput screening hit to highly potent and selective peroxisome proliferator-activated receptor δ (PPARδ) agonists are reported. The synthesis and structure−activity relationship in this series are described in detail. On the basis of a general schematic PPAR pharmacophore model, scaffold 1 was divided into headgroup, linker, and

  从高通量筛选到高效和选择性的过氧化物酶体增殖物激活受体δ（PPARδ）激动剂的发现，合成和优化了化合物1。详细介绍了该系列中的合成和构效关系。基于通用的PPAR药效团模型示意图，支架1将其分为头基，接头和尾基，并使用体外PPAR反式激活分析对PPAR激活进行了优化。有效和选择性的PPARδ活化需要一个（2-甲基苯氧基）乙酸头基，一个柔性连接基和一个带有两个疏水性芳基取代基的五元杂芳族中心环。这些芳基取代基的微调导致了一系列高效且选择性的化合物（例如化合物38c）在小鼠体内表现出出色的药代动力学特性。在体内急性给药模型中，该阵列的选定成员显示出可诱导丙酮酸脱氢酶激酶4（PDK4）和解偶联蛋白3（UCP3）的表达，这些基因已知参与能量稳态并受其调节。骨骼肌中的PPARδ。
• [EN] 4, 5-DIARYLTHIAZOLE DERIVATIVES AS CB-1 LIGANDS<br/>[FR] DERIVES DE 4, 5-DIARYLTHIAZOLE UTILISES EN TANT QUE LIGANDS DU CB-1
  申请人：ASTRAZENECA AB

  公开号：WO2004058255A1

  公开（公告）日：2004-07-15

  The present invention relates to compounds of formula (I): in which R1 and R2 independently represent phenyl, thienyl or pyridyl and R3 represents a group -X-Y-NR4R5 in which X is CO or SO2; Y is absent or represents NH and the other substituente are as defined in the description and their use in the treatment of obesity, psychiatric and neurological disorders and to pharmaceutical compositions containing them.

  本发明涉及以下式(I)的化合物：其中R1和R2分别表示苯基、噻吩基或吡啶基，R3表示一个基团-X-Y-NR4R5，其中X为CO或SO2；Y为不存在或表示NH，其他取代基如描述中所定义，并且它们在治疗肥胖、精神疾病和神经系统疾病以及含有它们的药物组合物中的应用。
• [EN] AQUEOUS DISPERSION COMPRISING STABLE NANOPARTICLES OF A WATER-INSOLUBLE THIAZOLE DERIVATIVE AND EXCIPIENTS LIKE MIDDLE CHAIN TRIGLYCERIDES<br/>[FR] DISPERSION AQUEUSE COMPRENANT DES NANOPARTICULES STABLES D'UN DERIVE DE THIAZOLE INSOLUBLE DANS L'EAU ET DES EXCIPIENTS TELS QUE DES TRIGLYCERIDES A CHAINE MOYENNE
  申请人：ASTRAZENECA AB

  公开号：WO2004069226A1

  公开（公告）日：2004-08-19

  A process for the preparation of a stable dispersion of solid particles, in an aqueous medium comprising combining (a) a first solution comprising a substantially water-insoluble substance which is a thiazole compound of Formula I, a water-miscible organic solvent and an inhibitor with (b) an aqueous phase comprising water and optionally a stabiliser, thereby precipitating solid particles comprising the inhibitor and the substantially water-insoluble substance; and optionally removing the water-miscible organic solvent; wherein the inhibitor is a non-polymeric hydrophobic organic compound as defined in the description. Also claimed are stable dispersions obtainable by the process, solid particles obtainable by the process and use of such particles. The process provides a dispersion of solid particles in an aqueous medium, which particles exhibit reduced or substantially no particle growth mediated by Ostwald ripening. The process is particlularly suitable for the preparation of small (sub-micron) aqueous dispersions of a substantially water-insoluble pharmacologically active substance.

  一种制备固体颗粒稳定分散液的方法，其中该液体是在水介质中混合（a）第一个溶液，该溶液包括一种公式I的噻唑化合物，它是一种基本上不溶于水的物质，还包括一种水溶性有机溶剂和一种抑制剂，以及（b）一种水相，其中包括水和可选的稳定剂，从而沉淀出包含抑制剂和基本上不溶于水的物质的固体颗粒；可选地去除水溶性有机溶剂；其中抑制剂是根据描述定义的非聚合疏水有机化合物。还声明了通过该过程获得的稳定分散液，通过该过程获得的固体颗粒以及使用这种颗粒。该过程提供了一种固体颗粒在水介质中的分散液，这些颗粒表现出通过奥斯特瓦尔德成核介导的减少或基本上没有颗粒生长。该过程特别适用于制备基本上不溶于水的药理活性物质的小（亚微米）水分散液。
• Thiazole compounds and pharmaceutical composition comprising the same
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US05217971A1

  公开（公告）日：1993-06-08

  Thiazole compounds of the formula ##STR1## wherein the substituents are defined herein are disclosed as having antithrombotic, vasodilating, antiallergic, antiinflammatory and 5-lipoxygenase inhibitory activity.

  本发明揭示了式##STR1##中所定义的取代基的噻唑化合物具有抗血栓、扩张血管、抗过敏、抗炎和5-脂氧合酶抑制活性。