8-chloro-2-(4-chlorophenyl)imidazo[1,2-a]pyrazine | 960116-30-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 8-chloro-2-(4-chlorophenyl)imidazo[1,2-a]pyrazine
• CAS: 960116-30-7
• 化学式: C₁₂H₇Cl₂N₃
• 分子量: 264.114
• InChiKey: ONHSMCWFAXMUSP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  30.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  8-chloro-2-(4-chlorophenyl)imidazo[1,2-a]pyrazine 在 N-碘代丁二酰亚胺 、 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 N-甲基吡咯烷酮 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 生成 8-((3-aminopropyl)amino)-2-(4-chlorophenyl)imidazo[1,2-a]pyrazine-5-carbonitrile
  参考文献：
  名称：

  Potency switch between CHK1 and MK2: Discovery of imidazo[1,2-a]pyrazine- and imidazo[1,2-c]pyrimidine-based kinase inhibitors

  摘要：

  Chemistry has been developed to access both imidazo[1,2-a]pyrazines and imidazo[1,2-c]pyrimidines. Small structural modifications in both series led to a switch of potency between two kinases involved in mediating cell cycle checkpoint control, CHK1 and MK2.

  DOI：

  10.1016/j.bmcl.2013.03.100
• 作为产物：
  描述：

  2-氯-3-氨基吡嗪 、 2,4'-二氯苯乙酮 以 乙腈 为溶剂， 反应 72.0h， 生成 8-chloro-2-(4-chlorophenyl)imidazo[1,2-a]pyrazine
  参考文献：
  名称：

  发现咪唑并[1,2- a ]吡嗪和吡唑并[1,5- c ]嘧啶作为TARPγ-8选择性AMPAR负调节剂

  摘要：

  该报告公开了咪唑并[1,2- a ]吡嗪和吡唑并[1,5- c ]嘧啶作为α-氨基-3-羟基-5-甲基异恶唑-4-丙酸酯受体（AMPARs）的选择性负调节剂的发现和表征。）与跨膜AMPAR调节蛋白γ-8相关。咪唑并吡嗪5最初被鉴定为有前途的γ-8选择性高通量筛选命中物，随后的结构-活性关系优化产生了纳摩尔级，脑渗透剂。用等位吡唑并嘧啶骨架替代咪唑并吡嗪核改善了微粒体稳定性和外排负债，从而提供26，JNJ-61432059。口服后26 在小鼠海马中显示出时间和剂量依赖性的AMPAR /γ-8受体占有率，从而在角膜点燃和戊四氮（PTZ）抗惊厥模型中产生了强大的癫痫发作保护作用。

  DOI：

  10.1021/acsmedchemlett.8b00599

文献信息

• WO2007/145921
  申请人：——

  公开号：——

  公开（公告）日：——
• IMIDAZOPYRAZINES AS PROTEIN KINASE INHIBITORS
  申请人：Zhao Lianyun

  公开号：US20080027063A1

  公开（公告）日：2008-01-31

  In its many embodiments, the present invention provides a novel class of imidazopyrazine compounds as inhibitors of protein and/or checkpoint kinases, methods of preparing such compounds, pharmaceutical compositions including one or more such compounds, methods of preparing pharmaceutical formulations including one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the protein or checkpoint kinases using such compounds or pharmaceutical compositions.
• US7557104B2
  申请人：——

  公开号：US7557104B2

  公开（公告）日：2009-07-07
• Discovery of Imidazo[1,2-<i>a</i>]pyrazines and Pyrazolo[1,5-<i>c</i>]pyrimidines as TARP γ-8 Selective AMPAR Negative Modulators
  作者：Brad M. Savall、Dongpei Wu、Devin M. Swanson、Mark Seierstad、Nyantsz Wu、Jorge Vives Martinez、Beatriz García Olmos、Brian Lord、Kevin Coe、Tatiana Koudriakova、Timothy W. Lovenberg、Nicholas I. Carruthers、Michael P. Maher、Michael K. Ameriks

  DOI：10.1021/acsmedchemlett.8b00599

  日期：2019.3.14

  This report discloses the discovery and characterization of imidazo[1,2-a]pyrazines and pyrazolo[1,5-c]pyrimidines as selective negative modulators of α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors (AMPARs) associated with transmembrane AMPAR regulatory protein γ-8. Imidazopyrazine 5 was initially identified as a promising γ-8 selective high-throughput screening hit, and subsequent structure–activity

  该报告公开了咪唑并[1,2- a ]吡嗪和吡唑并[1,5- c ]嘧啶作为α-氨基-3-羟基-5-甲基异恶唑-4-丙酸酯受体（AMPARs）的选择性负调节剂的发现和表征。）与跨膜AMPAR调节蛋白γ-8相关。咪唑并吡嗪5最初被鉴定为有前途的γ-8选择性高通量筛选命中物，随后的结构-活性关系优化产生了纳摩尔级，脑渗透剂。用等位吡唑并嘧啶骨架替代咪唑并吡嗪核改善了微粒体稳定性和外排负债，从而提供26，JNJ-61432059。口服后26 在小鼠海马中显示出时间和剂量依赖性的AMPAR /γ-8受体占有率，从而在角膜点燃和戊四氮（PTZ）抗惊厥模型中产生了强大的癫痫发作保护作用。
• Potency switch between CHK1 and MK2: Discovery of imidazo[1,2-a]pyrazine- and imidazo[1,2-c]pyrimidine-based kinase inhibitors
  作者：Zhaoyang Meng、Jeffrey P. Ciavarri、Andrew McRiner、Yinyan Zhao、Lianyun Zhao、Panduranga Adulla Reddy、Xingmin Zhang、Thierry O. Fischmann、Charles Whitehurst、M. Arshad Siddiqui

  DOI：10.1016/j.bmcl.2013.03.100

  日期：2013.5

  Chemistry has been developed to access both imidazo[1,2-a]pyrazines and imidazo[1,2-c]pyrimidines. Small structural modifications in both series led to a switch of potency between two kinases involved in mediating cell cycle checkpoint control, CHK1 and MK2.