2-(1H-pyrazol-4-yl)-5H-pyrrolo[2,3-b]pyrazine | 1604036-55-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡嗪类
• 英文名称: 2-(1H-pyrazol-4-yl)-5H-pyrrolo[2,3-b]pyrazine
• 英文别名: 2-(1H-pyrazol-4-yl)-5H-pyrrolo[3,2-b]pyrazine；2-(1h-Pyrazol-4-Yl)-5h-Pyrrolo[2,3-B]pyrazine
• CAS: 1604036-55-6
• 化学式: C₉H₇N₅
• 分子量: 185.188
• InChiKey: LTFQPYDMHBLAGZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  14
• 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：
  70.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(1H-pyrazol-4-yl)-5H-pyrrolo[2,3-b]pyrazine 在 N-碘代丁二酰亚胺 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 、 sodium hydride 作用下， 以 水 、 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 、 mineral oil 为溶剂， 反应 19.25h， 生成 2-(1H-pyrazol-4-yl)-7-(pyridin-3-yl)-5H-pyrrolo[2,3-b]pyrazine
  参考文献：
  名称：

  Fragment-based discovery of potent ERK2 pyrrolopyrazine inhibitors

  摘要：

  A fragment-based lead discovery approach was used to discover novel ERK2 inhibitors. The crystal structure of N-benzyl-9H-purin-6-amine 1 in complex with ERK2 elucidated its hinge-binding mode. In addition, the simultaneous binding of an imidazole molecule adjacent to 1 suggested a direction for fragment expansion. Structure-based core hopping applied to 1 led to 5H-pyrrolo[3,2-b] pyrazine (3) that afforded direct vectors to probe the pockets of interest while retaining the essential hinge binding elements. Utilizing the new vectors for SAR exploration, the new core 3 was quickly optimized to compound 39 resulting in a greater than 6600-fold improvement in potency. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.08.048
• 作为产物：
  描述：

  4-吡唑硼酸频哪醇酯 、 5-溴-4,7-二氮杂吲哚 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium carbonate 作用下， 以 乙腈 为溶剂， 反应 0.5h， 以0.63 g的产率得到2-(1H-pyrazol-4-yl)-5H-pyrrolo[2,3-b]pyrazine
  参考文献：
  名称：

  [EN] SERINE/THREONINE KINASE INHIBITORS
  [FR] INHIBITEURS DE LA SÉRINE/THRÉONINE KINASE

  摘要：

  具有化学式（I）的化合物，其中R1和R2如本文所定义，是ERK激酶的抑制剂。还披露了用于治疗过度增殖性疾病的组合物和方法。

  公开号：

  WO2014060395A1

文献信息

• SERINE/THREONINE KINASE INHIBITORS
  申请人：Genentech, Inc.

  公开号：US20150218176A1

  公开（公告）日：2015-08-06

  Compounds having the formula I wherein R 1 and R 2 are as defined herein are inhibitors of ERK kinase. Also disclosed are compositions and methods for treating hyperproliferative disorders.

  具有公式I的化合物，其中R1和R2的定义如本文所述，是ERK激酶的抑制剂。还披露了用于治疗过度增殖性疾病的组合物和方法。
• Substituted pyrrolo[2,3-b]pyrazines as serine/threonine kinase inhibitors
  申请人：Genentech, Inc.

  公开号：US09382257B2

  公开（公告）日：2016-07-05

  Compounds having the formula I wherein R1 and R2 are as defined herein are inhibitors of ERK kinase. Also disclosed are compositions and methods for treating hyperproliferative disorders.

  具有公式I的化合物，其中R1和R2的定义如本文所述，是ERK激酶的抑制剂。还揭示了治疗过度增殖性疾病的组合物和方法。
• EP2909206A1
  申请人：——

  公开号：EP2909206A1

  公开（公告）日：2015-08-26
• US9382257B2
  申请人：——

  公开号：US9382257B2

  公开（公告）日：2016-07-05
• Fragment-based discovery of potent ERK2 pyrrolopyrazine inhibitors
  作者：Daniel J. Burdick、Shumei Wang、Christopher Heise、Borlan Pan、Jake Drummond、JianPing Yin、Lauren Goeser、Steven Magnuson、Jeff Blaney、John Moffat、Weiru Wang、Huifen Chen

  DOI：10.1016/j.bmcl.2015.08.048

  日期：2015.11

  A fragment-based lead discovery approach was used to discover novel ERK2 inhibitors. The crystal structure of N-benzyl-9H-purin-6-amine 1 in complex with ERK2 elucidated its hinge-binding mode. In addition, the simultaneous binding of an imidazole molecule adjacent to 1 suggested a direction for fragment expansion. Structure-based core hopping applied to 1 led to 5H-pyrrolo[3,2-b] pyrazine (3) that afforded direct vectors to probe the pockets of interest while retaining the essential hinge binding elements. Utilizing the new vectors for SAR exploration, the new core 3 was quickly optimized to compound 39 resulting in a greater than 6600-fold improvement in potency. (C) 2015 Elsevier Ltd. All rights reserved.