1-[[1-(6-Propan-2-ylpyridin-2-yl)-2-quinolin-4-ylethylidene]amino]pyrrolidin-2-one | 476473-36-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1-[[1-(6-Propan-2-ylpyridin-2-yl)-2-quinolin-4-ylethylidene]amino]pyrrolidin-2-one
• 英文别名: 1-[[1-(6-propan-2-ylpyridin-2-yl)-2-quinolin-4-ylethylidene]amino]pyrrolidin-2-one
• CAS: 476473-36-6
• 化学式: C₂₃H₂₄N₄O
• 分子量: 372.47
• InChiKey: DGOBNTCPWWWALQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  58.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-[[1-(6-Propan-2-ylpyridin-2-yl)-2-quinolin-4-ylethylidene]amino]pyrrolidin-2-one 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-[2-(6-Isopropyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-quinoline
  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：

  Methyl 6-isopropylpicolinate 在 吡啶 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 生成 1-[[1-(6-Propan-2-ylpyridin-2-yl)-2-quinolin-4-ylethylidene]amino]pyrrolidin-2-one
  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

文献信息

• 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.