ethyl 2-methyl-5-[4-(methylsulfonyl)phenyl]-1-phenyl-1Hpyrrole-3-glyoxylate | 853055-03-5

• 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-methyl-5-[4-(methylsulfonyl)phenyl]-1-phenyl-1Hpyrrole-3-glyoxylate
• 英文别名: ethyl 2-[1-phenyl-2-methyl-5-[4-(methylsulfonyl)phenyl]-1H-pyrrol-3-yl]glyoxylate；ethyl-2-methyl-5-[(4-methylsulphonyl)phenyl]-1-phenyl-1H-pyrrole-3-glyoxylate；ethyl 2-[2-methyl-5-(4-methylsulfonylphenyl)-1-phenylpyrrol-3-yl]-2-oxoacetate
• CAS: 853055-03-5
• 化学式: C₂₂H₂₁NO₅S
• 分子量: 411.478
• InChiKey: ORFJJWLYLGOOLA-UHFFFAOYSA-N

物化性质

• 熔点：
  111 °C
• 沸点：
  626.7±55.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  90.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 2-methyl-5-[4-(methylsulfonyl)phenyl]-1-phenyl-1Hpyrrole-3-glyoxylate 在 三乙基硅烷 、 氢氧化钾 、 三氟乙酸 作用下， 以 乙醇 为溶剂， 反应 2.5h， 生成 2-methyl-5-[4-(methylsulfonyl)phenyl]-1-phenyl-1H-pyrrol-3-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 、 对甲苯磺酸 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 24.0h， 生成 ethyl 2-methyl-5-[4-(methylsulfonyl)phenyl]-1-phenyl-1Hpyrrole-3-glyoxylate
  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

• Novel Ester and Acid Derivatives of the 1,5-Diarylpyrrole Scaffold as Anti-Inflammatory and Analgesic Agents. Synthesis and in Vitro and in Vivo Biological Evaluation
  作者：Mariangela Biava、Giulio C. Porretta、Giovanna Poce、Claudio Battilocchio、Fabrizio Manetti、Maurizio Botta、Stefano Forli、Lidia Sautebin、Antonietta Rossi、Carlo Pergola、Carla Ghelardini、Nicoletta Galeotti、Francesco Makovec、Antonio Giordani、Paola Anzellotti、Paola Patrignani、Maurizio Anzini

  DOI：10.1021/jm901269y

  日期：2010.1.28

  (COX-2) inhibitors (coxibs) was developed to circumvent the major side effects of cyclooxygenase-1 (COX-1) and COX-2 inhibitors (stomach ulceration and nephrotoxicity). As a consequence, coxibs are extremely valuable in treating acute and chronic inflammatory conditions. However, the use of coxibs, such as rofecoxib (Vioxx), was discontinued because of the high risk of cardiovascular adverse events. More

  开发了新一代的选择性环氧合酶2（COX-2）抑制剂（coxibs），以规避环氧合酶1（COX-1）和COX-2抑制剂的主要副作用（胃溃疡和肾毒性）。结果，考昔布在治疗急性和慢性炎性疾病中非常有价值。但是，由于心血管不良事件的高风险，已停止使用罗非昔布（Vioxx）等考昔布。最近的临床发现强调了通过适当的COX-1与COX-2选择性可以如何缓解Coxib的心血管毒性。我们先前报道了一组对COX-2有选择性的取代的1,5-二芳基吡咯衍生物。在这里，我们描述了新的1,5-二芳基吡咯的合成及其在体外，离体的抑制作用，以及体内对COX同工酶及其止痛活性的研究。异丙基-2-甲基-5- [4-（甲基磺酰基）苯基] -1-苯基-1选择该系列的代表成员H-吡咯-3-乙酸酯（10a）进行药代动力学和代谢研究。
• 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.
• WO2008/14821
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis, in vitro, and in vivo biological evaluation and molecular docking simulations of chiral alcohol and ether derivatives of the 1,5-diarylpyrrole scaffold as novel anti-inflammatory and analgesic agents
  作者：Mariangela Biava、Giulio C. Porretta、Giovanna Poce、Sibilla Supino、Fabrizio Manetti、Stefano Forli、Maurizio Botta、Lidia Sautebin、Antonietta Rossi、Carlo Pergola、Carla Ghelardini、Monica Norcini、Francesco Makovec、Antonio Giordani、Paola Anzellotti、Roberto Cirilli、Rosella Ferretti、Bruno Gallinella、Francesco La Torre、Maurizio Anzini、Paola Patrignani

  DOI：10.1016/j.bmc.2008.07.058

  日期：2008.9

  Following our previous research on anti-inflammatory drugs (NSAIDs), we report here the synthesis of chiral 1,5-diarylpyrroles derivatives that were characterized for their in vitro inhibitory effects toward cyclooxygenase (COX) isozymes. Analysis of enzymatic affinity and COX-2 selectivity led us to the selection of one compound (+/-)-10b that was further tested in vitro in the human whole blood (HWB) and in vivo for its anti-inflammatory activity in mice. The affinity data have been rationalized through docking simulations. (C) 2008 Elsevier Ltd. All rights reserved.
• Novel Analgesic/Anti-Inflammatory Agents: Diarylpyrrole Acetic Esters Endowed with Nitric Oxide Releasing Properties
  作者：Mariangela Biava、Giulio Cesare Porretta、Giovanna Poce、Claudio Battilocchio、Salvatore Alfonso、Michele Rovini、Salvatore Valenti、Gianluca Giorgi、Vincenzo Calderone、Alma Martelli、Lara Testai、Lidia Sautebin、Antonietta Rossi、Giuseppina Papa、Carla Ghelardini、Lorenzo Di Cesare Mannelli、Antonio Giordani、Paola Anzellotti、Annalisa Bruno、Paola Patrignani、Maurizio Anzini

  DOI：10.1021/jm200715n

  日期：2011.11.24

  The design of compounds that are able to inhibit cyclooxygenase (COX) and to release nitric oxide (NO) should give rise to drugs endowed with an overall safer profile for the gastrointestinal and cardiovascular systems. Herein we report a new class of pyrrole-derived nitrooxy esters (11a-j), cyclooxygenase-2 (COX-2) selective inhibitors endowed with NO releasing properties, with the goal of generating new molecules able to both strongly inhibit this isoform and reduce the related adverse side effects. Taking into account the metabolic conversion of nitrooxy esters into corresponding alcohols, we also studied derivatives 12a-j. All compounds proved to be very potent and selective COX-2 inhibitors; nitrooxy derivatives displayed interesting ex vivo NO-dependent vasorelaxing properties. Compounds 11c, 11d, 12c, and 12d were selected for further in vivo studies that highlited good anti-inflammatory and antinociceptive activities. Finally, two selected compounds (11c and 12c) tested in human whole blood (HWB) assay proved to be preferential inhibitors of COX-2.