ethyl 2-[1-[6-(benzimidazol-1-yl)pyrazin-2-yl]pyrrol-3-yl]acetate | 875900-38-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: ethyl 2-[1-[6-(benzimidazol-1-yl)pyrazin-2-yl]pyrrol-3-yl]acetate
• CAS: 875900-38-2
• 化学式: C₁₉H₁₇N₅O₂
• 分子量: 347.376
• InChiKey: DMMZTRYCNKHXEX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.71
• 重原子数：
  26.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  74.83
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  ethyl 2-[1-[6-(benzimidazol-1-yl)pyrazin-2-yl]pyrrol-3-yl]acetate 在 水 、 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 生成 2-[1-[6-(Benzimidazol-1-yl)pyrazin-2-yl]pyrrol-3-yl]acetic acid
  参考文献：
  名称：

  Discovery and structure–activity relationship of 2,6-disubstituted pyrazines, potent and selective inhibitors of protein kinase CK2

  摘要：

  We report the discovery and structure-activity relationship of 2,6-disubstituted pyrazines, which are potent and selective CK2 inhibitors. Lead compound 1 was identified, and derivatives were prepared to develop potent inhibitory activity. As a result, we obtained compound 7, which was the smallest unit that retained potency. Then, introducing an aminoalkyl group at the 6-position of the indazole ring resulted in improved efficacy in both enzymatic and cell-based CK2 inhibition assays. Moreover, compound 13 showed selectivity against other kinases and in vivo efficacy in a rat nephritis model. These results show that 2,6-disubstituted pyrazines have potential as therapeutic agents for nephritis. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.006
• 作为产物：
  描述：

  ethyl 1-(triisopropylsilyl)-3-pyrrolylglyoxalate 在 potassium phosphate 、 copper(l) iodide 、 sodium hypophosphite 、 palladium on carbon 、 (1S,2S)-(+)-1,2-环己二胺 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 48.0h， 生成 ethyl 2-[1-[6-(benzimidazol-1-yl)pyrazin-2-yl]pyrrol-3-yl]acetate
  参考文献：
  名称：

  Discovery and structure–activity relationship of 2,6-disubstituted pyrazines, potent and selective inhibitors of protein kinase CK2

  摘要：

  We report the discovery and structure-activity relationship of 2,6-disubstituted pyrazines, which are potent and selective CK2 inhibitors. Lead compound 1 was identified, and derivatives were prepared to develop potent inhibitory activity. As a result, we obtained compound 7, which was the smallest unit that retained potency. Then, introducing an aminoalkyl group at the 6-position of the indazole ring resulted in improved efficacy in both enzymatic and cell-based CK2 inhibition assays. Moreover, compound 13 showed selectivity against other kinases and in vivo efficacy in a rat nephritis model. These results show that 2,6-disubstituted pyrazines have potential as therapeutic agents for nephritis. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.006