ethyl 2-[1-(2-methyl-5-(4-methylsulphonyl)phenyl)-4-(trifluoromethyl)phenyl-1H-pyrrol-3-yl]acetate | 853055-08-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: ethyl 2-[1-(2-methyl-5-(4-methylsulphonyl)phenyl)-4-(trifluoromethyl)phenyl-1H-pyrrol-3-yl]acetate
• 英文别名: ethyl 2-methyl-5-[4-(methylsulfonyl)phenyl]-1-[4-(trifluoromethyl)phenyl]-1H-pyrrole-3-acetate；ethyl 2-[2-methyl-5-(4-methylsulfonylphenyl)-1-[4-(trifluoromethyl)phenyl]pyrrol-3-yl]acetate
• CAS: 853055-08-0
• 化学式: C₂₃H₂₂F₃NO₄S
• 分子量: 465.493
• InChiKey: ZKJFNNNFBXEDAX-UHFFFAOYSA-N

物化性质

• 熔点：
  90-92 °C
• 沸点：
  572.1±50.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  73.8
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 2-[1-(2-methyl-5-(4-methylsulphonyl)phenyl)-4-(trifluoromethyl)phenyl-1H-pyrrol-3-yl]acetate 在 氢氧化钾 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以66%的产率得到2-[1-(2-methyl-5-(4-methylsulphonyl)phenyl)-4-(trifluoromethyl)phenyl-1H-pyrrol-3-yl]acetic acid
  参考文献：
  名称：

  1,5-Diarylpyrrole-3-acetic Acids and Esters as Novel Classes of Potent and Highly Selective Cyclooxygenase-2 Inhibitors

  摘要：

  A small set of substituted 1,5-diarylpyrrole-3-acetic and -glyoxylic acid derivatives have been synthesized, and their cyclooxygenase (COX-1 and COX-2) inhibiting properties have been evaluated. Some compounds proved to be highly selective COX-2 inhibitors, and their affinity data have been rationalized through docking simulations in terms of interactions with a crystallographic model of the COX-2 binding site.

  DOI：

  10.1021/jm049121q
• 作为产物：
  描述：

  1-[4-(methylsulfonyl)phenyl]pentane-1,4-dione 在 吡啶 、 三乙基硅烷 、 对甲苯磺酸 、 三氟乙酸 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 24.5h， 生成 ethyl 2-[1-(2-methyl-5-(4-methylsulphonyl)phenyl)-4-(trifluoromethyl)phenyl-1H-pyrrol-3-yl]acetate
  参考文献：
  名称：

  1,5-Diarylpyrrole-3-acetic Acids and Esters as Novel Classes of Potent and Highly Selective Cyclooxygenase-2 Inhibitors

  摘要：

  A small set of substituted 1,5-diarylpyrrole-3-acetic and -glyoxylic acid derivatives have been synthesized, and their cyclooxygenase (COX-1 and COX-2) inhibiting properties have been evaluated. Some compounds proved to be highly selective COX-2 inhibitors, and their affinity data have been rationalized through docking simulations in terms of interactions with a crystallographic model of the COX-2 binding site.

  DOI：

  10.1021/jm049121q

文献信息

• Synthesis, Biological Evaluation, and Enzyme Docking Simulations of 1,5-Diarylpyrrole-3-Alkoxyethyl Ethers as Selective Cyclooxygenase-2 Inhibitors Endowed with Anti-inflammatory and Antinociceptive Activity
  作者：Maurizio Anzini、Michele Rovini、Andrea Cappelli、Salvatore Vomero、Fabrizio Manetti、Maurizio Botta、Lidia Sautebin、Antonietta Rossi、Carlo Pergola、Carla Ghelardini、Monica Norcini、Antonio Giordani、Francesco Makovec、Paola Anzellotti、Paola Patrignani、Mariangela Biava

  DOI：10.1021/jm800084s

  日期：2008.8.1

  comparable COX-2 selectivity to valdecoxib, while it was more selective than celecoxib but less selective than rofecoxib. The potential anti-inflammatory and antinociceptive activities of compounds 7a, 8a, and 8d were evaluated in vivo, where they showed a very good activity against both carrageenan-induced hyperalgesia and edema in the rat paw test. In the abdominal constriction test compound 7a, 8a, and

  合成了一系列取代的1,5-二芳基吡咯-3-烷氧基乙基醚（6、7和8），目的是评估先前报道的1,5-二芳基吡咯衍生物（5）是否取代了乙酸酯具有烷氧基乙基的部分仍可产生新的，高选择性和有效的COX-2抑制剂。在体外细胞培养测定中，所有化合物均被证明是有效的选择性COX-2抑制剂。在人全血（HWB）分析中，化合物8a对valdecoxib具有相当的COX-2选择性，而比celecoxib更具选择性，但与rofecoxib相比选择性较低。在体内评估了化合物7a，8a和8d的潜在抗炎和镇痛活性，在鼠爪试验中，它们对角叉菜胶引起的痛觉过敏和浮肿均显示出非常好的活性。在腹部收缩试验中，化合物7a，8a和8d能够以统计学上显着的方式减少扭曲的次数。此外，这些化合物的亲和力数据已通过酶对接模拟，通过与Autoxock 3.0.5，GRID 21和MacroModel 8.5结合使用的复合物软件包，与COX-
• 3-SUBSTITUTED-1,5-DIARLY-2-ALKYL-PYRROLES HIGHLY SELECTIVE AND ORALLY EFFECTIVE COX-2 INHIBITORS
  申请人：Cappelli Andrea

  公开号：US20090264500A1

  公开（公告）日：2009-10-22

  This invention relates to 3-substituted-1,5-diaryl-2-alkyl-pyrroles of Formula I, pharmaceutical compositions containing them, and to their use for the pharmacological treatment of pain and COX-2 over-activation associated disorders. Compounds of this invention are new pyrrole derivatives bearing in position-3 of the pyrrole ring, several variously functionalized, not aliphatic, side chains which confer to the compounds a relevant COX-2 potency and selectivity along with a remarkable oral efficacy. Phenyl rings in position-1 and -5 are variously substituted, but compounds of particular interest are those substituted in position-5 with 4-methylsulphonyl-phenyl or with 4-aminosulphonyl-phenyl groups.

  本发明涉及式I的3-取代-1,5-二芳基-2-烷基-吡咯衍生物，包含它们的药物组合物，以及它们用于治疗与疼痛和COX-2过度激活相关的疾病的药理学治疗。本发明的化合物是新的吡咯衍生物，在吡咯环的3位上带有几个不同官能团化的非脂肪侧链，这些侧链赋予化合物显著的COX-2效力和选择性以及卓越的口服效力。在1位和5位的苯环上有不同的取代基，但特别感兴趣的化合物是在5位上用4-甲基磺酰基苯基或4-氨基磺酰基苯基基团取代的化合物。
• US7906551B2
  申请人：——

  公开号：US7906551B2

  公开（公告）日：2011-03-15
• 1,5-Diarylpyrrole-3-acetic Acids and Esters as Novel Classes of Potent and Highly Selective Cyclooxygenase-2 Inhibitors
  作者：Mariangela Biava、Giulio Cesare Porretta、Andrea Cappelli、Salvatore Vomero、Fabrizio Manetti、Maurizio Botta、Lidia Sautebin、Antonietta Rossi、Francesco Makovec、Maurizio Anzini

  DOI：10.1021/jm049121q

  日期：2005.5.1

  A small set of substituted 1,5-diarylpyrrole-3-acetic and -glyoxylic acid derivatives have been synthesized, and their cyclooxygenase (COX-1 and COX-2) inhibiting properties have been evaluated. Some compounds proved to be highly selective COX-2 inhibitors, and their affinity data have been rationalized through docking simulations in terms of interactions with a crystallographic model of the COX-2 binding site.