N-{4-[5-(4-fluorophenyl)-3-(2-methylsulfanylethyl)-2-thioxo-2,3-dihydro-1H-imidazol-4-yl]pyridin-2-yl}acetamide | 820241-47-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-{4-[5-(4-fluorophenyl)-3-(2-methylsulfanylethyl)-2-thioxo-2,3-dihydro-1H-imidazol-4-yl]pyridin-2-yl}acetamide
• 英文别名: N-[4-[5-(4-fluorophenyl)-3-(2-methylsulfanylethyl)-2-sulfanylidene-1H-imidazol-4-yl]pyridin-2-yl]acetamide
• CAS: 820241-47-2
• 化学式: C₁₉H₁₉FN₄OS₂
• 分子量: 402.516
• InChiKey: VWKYFTRJWQANBU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-methylsulfinylbenzyl chloride 、 N-{4-[5-(4-fluorophenyl)-3-(2-methylsulfanylethyl)-2-thioxo-2,3-dihydro-1H-imidazol-4-yl]pyridin-2-yl}acetamide 在 sodium carbonate 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以58%的产率得到N-{4-[5-(4-fluorophenyl)-2-(4-methylsulfinylbenzylsulfanyl)-3-(2-methylsulfanylethyl)-3H-imidazol-4-yl]pyridin-2-yl}acetamide
  参考文献：
  名称：

  Tetrasubstituted Imidazole Inhibitors of Cytokine Release:  Probing Substituents in the N-1 Position

  摘要：

  We prepared novel 1,2,4,5-tetrasubstituted imidazole derivatives with high anti-inflammatory activity by using our previously described regiospecific synthesis. Systematic optimization of the imidazole N-1 substituent resulted in compound 9b that potently inhibited the mitogen-activated protein kinase p38 (p38 IC50 = 0.218 muM) as well as the release of the proinflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor alpha. (TNFalpha) from human whole blood after stimulation with LPS. Furthermore, compound 9b exhibited reduced cytochrome P450 interaction in comparison with SB203580. This result is particularly important, since cytochrome P450 interaction is observed for some p38 inhibitors and in turn can potentially cause drug-drug interaction or lead to other hepatic changes such as P450 enzyme induction.

  DOI：

  10.1021/jm0496584
• 作为产物：
  描述：

  2-乙酰基氨基异烟酸 在 4-二甲氨基吡啶 、 2,2,4,4-四甲基-1,3-环丁烷二硫酮 、 氢溴酸 、 sodium methylate 、 N,N'-羰基二咪唑 、 亚硝酸异戊酯 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 49.75h， 生成 N-{4-[5-(4-fluorophenyl)-3-(2-methylsulfanylethyl)-2-thioxo-2,3-dihydro-1H-imidazol-4-yl]pyridin-2-yl}acetamide
  参考文献：
  名称：

  Tetrasubstituted Imidazole Inhibitors of Cytokine Release:  Probing Substituents in the N-1 Position

  摘要：

  We prepared novel 1,2,4,5-tetrasubstituted imidazole derivatives with high anti-inflammatory activity by using our previously described regiospecific synthesis. Systematic optimization of the imidazole N-1 substituent resulted in compound 9b that potently inhibited the mitogen-activated protein kinase p38 (p38 IC50 = 0.218 muM) as well as the release of the proinflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor alpha. (TNFalpha) from human whole blood after stimulation with LPS. Furthermore, compound 9b exhibited reduced cytochrome P450 interaction in comparison with SB203580. This result is particularly important, since cytochrome P450 interaction is observed for some p38 inhibitors and in turn can potentially cause drug-drug interaction or lead to other hepatic changes such as P450 enzyme induction.

  DOI：

  10.1021/jm0496584