2-(hydroxymethyl)-4,5-bis(4-methoxyphenyl)thiazole | 130717-64-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(hydroxymethyl)-4,5-bis(4-methoxyphenyl)thiazole
• 英文别名: [4,5-bis(4-methoxyphenyl)thiazol-2-yl]methanol；[4,5-bis-(4-methoxy-phenyl)-thiazol-2-yl]-methanol；4,5-Bis(4-methoxyphenyl)-2-hydroxymethylthiazole；[4,5-bis(4-methoxyphenyl)-1,3-thiazol-2-yl]methanol
• CAS: 130717-64-5
• 化学式: C₁₈H₁₇NO₃S
• 分子量: 327.404
• InChiKey: VQTVOLWHOFLSFF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  79.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(hydroxymethyl)-4,5-bis(4-methoxyphenyl)thiazole 在 manganese dioxide 正己烷 作用下， 以 乙酸乙酯 为溶剂， 反应 5.5h， 以to give 4,5-bis(4-methoxyphenyl)-2-formylthiazol (3.25 g)的产率得到2-formyl-4,5-bis(4-methoxyphenyl)thiazole
  参考文献：
  名称：

  Thiazole compounds and pharmaceutical composition comprising the same

  摘要：

  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。

  公开号：

  US05217971A1
• 作为产物：
  描述：

  茴香偶姻 在 lithium aluminium tetrahydride 、 氯化亚砜 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 5.5h， 生成 2-(hydroxymethyl)-4,5-bis(4-methoxyphenyl)thiazole
  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。
• 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。
• Compounds And Compositions As Ppar Modulators
  申请人：Epple Robert

  公开号：US20070203155A1

  公开（公告）日：2007-08-30

  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.

  本发明提供了化合物、包含这些化合物的药物组合物以及使用这些化合物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障碍的方法，特别是与PPAR的活性相关的疾病或障碍的方法。
• Thiazole compounds, processes for the preparation thereof, and pharmaceutical composition comprising the same
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP0377457A1

  公开（公告）日：1990-07-11

  The present invention relates to new thiazole compounds and pharmaceutically acceptable salts thereof which have pharmacological activities, processes for preparation thereof, a pharmaceutical composition comprising the same same and a use of the same.

  本发明涉及具有药理活性的新噻唑化合物及其药学上可接受的盐、其制备工艺、包含相同物质的药物组合物以及相同物质的用途。