ethyl 2-[1-(6-iodopyrazin-2-yl)-1H-pyrrol-3-yl]acetate | 875900-08-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 2-[1-(6-iodopyrazin-2-yl)-1H-pyrrol-3-yl]acetate
• 英文别名: Ethyl 2-[1-(6-iodopyrazin-2-yl)pyrrol-3-yl]acetate
• CAS: 875900-08-6
• 化学式: C₁₂H₁₂IN₃O₂
• 分子量: 357.151
• InChiKey: VJUODNYJPSFSJF-UHFFFAOYSA-N

物化性质

• 沸点：
  444.1±45.0 °C(Predicted)
• 密度：
  1.70±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  57
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 2-[1-(6-iodopyrazin-2-yl)-1H-pyrrol-3-yl]acetate 在 potassium phosphate 、 copper(l) iodide 、 (1S,2S)-(+)-1,2-环己二胺 、 水 、 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 24.0h， 生成 2-[1-[6-(6-Chloroindazol-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 24.0h， 生成 ethyl 2-[1-(6-iodopyrazin-2-yl)-1H-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

文献信息

• Structure-Activity Relationships of Pyrazine-Based CK2 Inhibitors: Synthesis and Evaluation of 2,6-Disubstituted Pyrazines and 4,6-Disubstituted Pyrimidines
  作者：Yamato Suzuki、Jérôme Cluzeau、Takafumi Hara、Akira Hirasawa、Gozoh Tsujimoto、Shinya Oishi、Hiroaki Ohno、Nobutaka Fujii

  DOI：10.1002/ardp.200700269

  日期：2008.9

  Structually related to the known CK2 inhibitors, 2,6‐disubstituted pyrazine and 4,6‐disubstituted pyrimidine derivatives were synthesized and their inhibitory activities toward CK2α and CK2α′ were evaluated. Structure‐activity relationship study has revealed that several pyrazine derivatives bearing a (pyrrol‐3‐yl)acetic acid and a monosubstituted aniline possess potent inhibitory activities.

  与已知的 CK2 抑制剂结构相关，合成了 2,6-二取代吡嗪和 4,6-二取代嘧啶衍生物，并评估了它们对 CK2α 和 CK2α' 的抑制活性。构效关系研究表明，几种带有（吡咯-3-基）乙酸和单取代苯胺的吡嗪衍生物具有有效的抑制活性。