2-(3,4-Difluorophenyl)-1-(6-methylpyridin-2-yl)ethanone | 476472-54-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(3,4-Difluorophenyl)-1-(6-methylpyridin-2-yl)ethanone
• CAS: 476472-54-5
• 化学式: C₁₄H₁₁F₂NO
• 分子量: 247.244
• InChiKey: ORMSKVKQKNOZIS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  30
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(3,4-Difluorophenyl)-1-(6-methylpyridin-2-yl)ethanone 在 吡啶 、 sodium hydride 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 3-(3,4-difluoro-phenyl)-2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole
  参考文献：
  名称：

  Synthesis and activity of new aryl- and heteroaryl-substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole inhibitors of the transforming growth factor-β type I receptor kinase domain

  摘要：

  We have expanded our previously reported series of pyrazole-based inhibitors of the TGF-beta type I receptor kinase domain (TbetaR-I) to now include new 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole analogues. Limited examination of the SAR of this new series in both enzyme and cell based in vitro assays has revealed selectivity differences with respect to p38 MAP kinase (p38 MAPK) depending on the nature of the 'warhead' group on the dihydropyrrolopyrazole ring. As with our original pyrazole series, phenyl substituents tended to show greater selectivity against p38 MAPK than those comprised of the quinoline-4-yl moiety. We have also achieved co-crystallization and X-ray analysis of compounds 3 and 15, two potent examples of this new series, with the TbetaR-I receptor kinase domain.

  DOI：

  10.1016/j.bmcl.2004.04.007
• 作为产物：
  描述：

  6-甲基-2-吡啶甲酸甲酯 在 盐酸 、 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 60.0h， 生成 2-(3,4-Difluorophenyl)-1-(6-methylpyridin-2-yl)ethanone
  参考文献：
  名称：

  Synthesis and Activity of New Aryl- and Heteroaryl-Substituted Pyrazole Inhibitors of the Transforming Growth Factor-β Type I Receptor Kinase Domain

  摘要：

  Pyrazole-based inhibitors of the transforming growth factor-beta type I receptor kinase domain (TbetaR-I) are described. Examination of the SAP, in both enzyme- and cell-based in vitro assays resulted in the emergence of two subseries featuring differing selectivity versus p38 MAP kinase. A common binding mode at the active site has been established by successful cocrystallization and X-ray analysis of potent inhibitors with the TbetaR-I receptor kinase domain.

  DOI：

  10.1021/jm0205705

文献信息

• Synthesis and Activity of New Aryl- and Heteroaryl-Substituted Pyrazole Inhibitors of the Transforming Growth Factor-β Type I Receptor Kinase Domain
  作者：J. Scott Sawyer、Bryan D. Anderson、Douglas W. Beight、Robert M. Campbell、Michael L. Jones、David K. Herron、John W. Lampe、Jefferson R. McCowan、William T. McMillen、Nicholas Mort、Stephen Parsons、Edward C. R. Smith、Michal Vieth、Leonard C. Weir、Lei Yan、Faming Zhang、Jonathan M. Yingling

  DOI：10.1021/jm0205705

  日期：2003.9.1

  Pyrazole-based inhibitors of the transforming growth factor-beta type I receptor kinase domain (TbetaR-I) are described. Examination of the SAP, in both enzyme- and cell-based in vitro assays resulted in the emergence of two subseries featuring differing selectivity versus p38 MAP kinase. A common binding mode at the active site has been established by successful cocrystallization and X-ray analysis of potent inhibitors with the TbetaR-I receptor kinase domain.
• NOVEL PYRROLE DERIVATIVES AS PHARMACEUTICAL AGENTS
  申请人：ELI LILLY AND COMPANY

  公开号：EP1397364B1

  公开（公告）日：2007-07-25
• Synthesis and activity of new aryl- and heteroaryl-substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole inhibitors of the transforming growth factor-β type I receptor kinase domain
  作者：J. Scott Sawyer、Douglas W. Beight、Karen S. Britt、Bryan D. Anderson、Robert M. Campbell、Theodore Goodson、David K. Herron、Hong-Yu Li、William T. McMillen、Nicholas Mort、Stephen Parsons、Edward C.R. Smith、Jill R. Wagner、Lei Yan、Faming Zhang、Jonathan M. Yingling

  DOI：10.1016/j.bmcl.2004.04.007

  日期：2004.7

  We have expanded our previously reported series of pyrazole-based inhibitors of the TGF-beta type I receptor kinase domain (TbetaR-I) to now include new 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole analogues. Limited examination of the SAR of this new series in both enzyme and cell based in vitro assays has revealed selectivity differences with respect to p38 MAP kinase (p38 MAPK) depending on the nature of the 'warhead' group on the dihydropyrrolopyrazole ring. As with our original pyrazole series, phenyl substituents tended to show greater selectivity against p38 MAPK than those comprised of the quinoline-4-yl moiety. We have also achieved co-crystallization and X-ray analysis of compounds 3 and 15, two potent examples of this new series, with the TbetaR-I receptor kinase domain.