2-{1-[6-(1H-indol-1-yl)pyrazin-2-yl]-1H-pyrrol-3-yl}acetic acid | 875900-14-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2-{1-[6-(1H-indol-1-yl)pyrazin-2-yl]-1H-pyrrol-3-yl}acetic acid
• 英文别名: 2-[1-(6-Indol-1-ylpyrazin-2-yl)pyrrol-3-yl]acetic acid
• CAS: 875900-14-4
• 化学式: C₁₈H₁₄N₄O₂
• 分子量: 318.335
• InChiKey: TXGBBPFLTDJWOZ-UHFFFAOYSA-N

物化性质

• 沸点：
  520.9±50.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  72.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  ethyl 2-[1-(6-indol-1-ylpyrazin-2-yl)pyrrol-3-yl]acetate 在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 以53 mg的产率得到2-{1-[6-(1H-indol-1-yl)pyrazin-2-yl]-1H-pyrrol-3-yl}acetic acid
  参考文献：
  名称：

  基于吡嗪的 CK2 抑制剂的构效关系：2,6-二取代吡嗪和 4,6-二取代嘧啶的合成与评价

  摘要：

  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。

  DOI：

  10.1002/ardp.200700269

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。
• Discovery and structure–activity relationship of 2,6-disubstituted pyrazines, potent and selective inhibitors of protein kinase CK2
  作者：Nobuhiro Fuchi、Yosuke Iura、Hiroaki Kaneko、Aiko Nitta、Kazuharu Suyama、Hiroshi Ueda、Shinichi Yamaguchi、Kazumi Nishimura、Shigeo Fujii、Yumiko Sekiya、Masateru Yamada、Toshiya Takahashi

  DOI：10.1016/j.bmcl.2012.05.006

  日期：2012.7

  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.