Di-tert-butyl 1-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazine-1,2-dicarboxylate | 1421338-19-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Di-tert-butyl 1-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazine-1,2-dicarboxylate
• 英文别名: tert-butyl N-[5-(4-methylphenyl)sulfonylpyrrolo[2,3-b]pyrazin-2-yl]-N-[(2-methylpropan-2-yl)oxycarbonylamino]carbamate
• CAS: 1421338-19-3
• 化学式: C₂₃H₂₉N₅O₆S
• 分子量: 503.579
• InChiKey: XSQNAVGLZHDCCO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  141
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Di-tert-butyl 1-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazine-1,2-dicarboxylate 在 磷酸 、 potassium carbonate 作用下， 以 四氢呋喃 、 正庚烷 、 水 为溶剂， 反应 3.0h， 以94%的产率得到2-hydrazinyl-5-tosyl-5H-pyrrolo[2,3-b]pyrazine
  参考文献：
  名称：

  Design and synthesis of tricyclic cores for kinase inhibition

  摘要：

  Interest in therapeutic kinase inhibitors continues to grow beyond success in oncology. To date, ATP-mimetic kinase inhibitors have focused primarily on monocyclic and bicyclic heterocyclic cores. We sought to expand on the repertoire of potential cores for kinase inhibition by exploring tricyclic variants of classical bicyclic hinge binding motifs such as pyrrolopyridine and pyrrolopyrazine. Herein we describe the syntheses of eight alternative tricyclic cores as well as in vitro screening results for representative kinases of potential therapeutic interest. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.11.108
• 作为产物：
  描述：

  5-溴-3-((三甲基硅基)乙炔)吡嗪-2-胺 在 palladium diacetate 、 sodium hydride 、 potassium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 1,4-二氧六环 、 2-甲基-2-丁醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 Di-tert-butyl 1-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazine-1,2-dicarboxylate
  参考文献：
  名称：

  Design and synthesis of tricyclic cores for kinase inhibition

  摘要：

  Interest in therapeutic kinase inhibitors continues to grow beyond success in oncology. To date, ATP-mimetic kinase inhibitors have focused primarily on monocyclic and bicyclic heterocyclic cores. We sought to expand on the repertoire of potential cores for kinase inhibition by exploring tricyclic variants of classical bicyclic hinge binding motifs such as pyrrolopyridine and pyrrolopyrazine. Herein we describe the syntheses of eight alternative tricyclic cores as well as in vitro screening results for representative kinases of potential therapeutic interest. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.11.108

文献信息

• Design and synthesis of tricyclic cores for kinase inhibition
  作者：Stacy Van Epps、Bryan Fiamengo、Jeremy Edmunds、Anna Ericsson、Kristine Frank、Michael Friedman、Dawn George、Jonathan George、Eric Goedken、Brian Kotecki、Gloria Martinez、Philip Merta、Michael Morytko、Shashank Shekhar、Barbara Skinner、Kent Stewart、Jeffrey Voss、Grier Wallace、Lu Wang、Lu Wang、Neil Wishart

  DOI：10.1016/j.bmcl.2012.11.108

  日期：2013.2

  Interest in therapeutic kinase inhibitors continues to grow beyond success in oncology. To date, ATP-mimetic kinase inhibitors have focused primarily on monocyclic and bicyclic heterocyclic cores. We sought to expand on the repertoire of potential cores for kinase inhibition by exploring tricyclic variants of classical bicyclic hinge binding motifs such as pyrrolopyridine and pyrrolopyrazine. Herein we describe the syntheses of eight alternative tricyclic cores as well as in vitro screening results for representative kinases of potential therapeutic interest. (c) 2012 Elsevier Ltd. All rights reserved.
• Structure activity optimization of 6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazines as Jak1 kinase inhibitors
  作者：Michael Friedman、Kristine E. Frank、Ana Aguirre、Maria A. Argiriadi、Heather Davis、Jeremy J. Edmunds、Dawn M. George、Jonathan S. George、Eric Goedken、Bryan Fiamengo、Deborah Hyland、Bin Li、Anwar Murtaza、Michael Morytko、Gagandeep Somal、Kent Stewart、Edit Tarcsa、Stacy Van Epps、Jeffrey Voss、Lu Wang、Kevin Woller、Neil Wishart

  DOI：10.1016/j.bmcl.2015.09.020

  日期：2015.10

  Previous work investigating tricyclic pyrrolopyrazines as kinase cores led to the discovery that 1-cyclohexyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine (12) had Jak inhibitory activity. Herein we describe our initial efforts to develop orally bioavailable analogs of 12 with improved selectivity of Jak1 over Jak2. (C) 2015 Elsevier Ltd. All rights reserved.