2-methyl-1-[4-(methylsulfonyl)phenyl]-5-[3,4-(difluoro)phenyl]-1H-pyrrole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 2-methyl-1-[4-(methylsulfonyl)phenyl]-5-[3,4-(difluoro)phenyl]-1H-pyrrole
• 英文别名: 2-(3,4-Difluorophenyl)-5-methyl-1-(4-methylsulfonylphenyl)pyrrole
• 化学式: C₁₈H₁₅F₂NO₂S
• 分子量: 347.385
• InChiKey: QQFAOMYDGWJNID-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  47.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-methyl-1-[4-(methylsulfonyl)phenyl]-5-[3,4-(difluoro)phenyl]-1H-pyrrole 、 草酰氯单乙酯 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 以80%的产率得到Ethyl 2-[5-(3,4-difluorophenyl)-2-methyl-1-(4-methylsulfonylphenyl)pyrrol-3-yl]-2-oxoacetate
  参考文献：
  名称：

  Cyclooxygenase-2 Inhibitors. 1,5-Diarylpyrrol-3-acetic Esters with Enhanced Inhibitory Activity toward Cyclooxygenase-2 and Improved Cyclooxygenase-2/Cyclooxygenase-1 Selectivity

  摘要：

  The important role of cyclooxygenase-2 (COX-2) in the pathogenesis of inflammation and side effect limitations of current COX-2 inhibitor drugs illustrates a need for the design of new con pounds based on alternative structural templates. We previously reported a set of substituted 1,5-diarylpyrrole derivatives, along with their inhibitory activity toward COX enzymes. Several compounds proved to be highly selective COX-2 inhibitors and their affinity data were rationalized through docking simulations. In this paper, we describe the synthesis of new 1,5-diary lpyrrole derivatives that were assayed for their in vitro inhibitory effects toward COX isozymes. Among them, the ethyl-2-methyl-5-[4-(methylsulfonyl)phenyl]-1-[3-fluorophenyl]-1H-pyrrol-3-acetate (1d), which was the most potent and COX-2 selective compound, also showed a very interesting in vivo anti-inflammatory and analgesic activity, laying the foundations for developing new lead compounds that could be effective agents in the armamentarium for the management of inflammation and pain.

  DOI：

  10.1021/jm0707525
• 作为产物：
  描述：

  1-(3,4-Difluorophenyl)pentane-1,4-dione 、 4-甲磺酰基苯胺 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 20.0h， 以78%的产率得到2-methyl-1-[4-(methylsulfonyl)phenyl]-5-[3,4-(difluoro)phenyl]-1H-pyrrole
  参考文献：
  名称：

  Cyclooxygenase-2 Inhibitors. 1,5-Diarylpyrrol-3-acetic Esters with Enhanced Inhibitory Activity toward Cyclooxygenase-2 and Improved Cyclooxygenase-2/Cyclooxygenase-1 Selectivity

  摘要：

  The important role of cyclooxygenase-2 (COX-2) in the pathogenesis of inflammation and side effect limitations of current COX-2 inhibitor drugs illustrates a need for the design of new con pounds based on alternative structural templates. We previously reported a set of substituted 1,5-diarylpyrrole derivatives, along with their inhibitory activity toward COX enzymes. Several compounds proved to be highly selective COX-2 inhibitors and their affinity data were rationalized through docking simulations. In this paper, we describe the synthesis of new 1,5-diary lpyrrole derivatives that were assayed for their in vitro inhibitory effects toward COX isozymes. Among them, the ethyl-2-methyl-5-[4-(methylsulfonyl)phenyl]-1-[3-fluorophenyl]-1H-pyrrol-3-acetate (1d), which was the most potent and COX-2 selective compound, also showed a very interesting in vivo anti-inflammatory and analgesic activity, laying the foundations for developing new lead compounds that could be effective agents in the armamentarium for the management of inflammation and pain.

  DOI：

  10.1021/jm0707525