11-(3-imino-5,6-dihydro-3H-benzo[h]cinnolin-2-yl)-undecanoic acid | 402519-05-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 11-(3-imino-5,6-dihydro-3H-benzo[h]cinnolin-2-yl)-undecanoic acid
• 英文别名: 11-(3-Imino-5,6-dihydrobenzo[h]cinnolin-2-yl)undecanoic acid
• CAS: 402519-05-5
• 化学式: C₂₃H₃₁N₃O₂
• 分子量: 381.518
• InChiKey: URXMXVZNXCQDAO-UHFFFAOYSA-N

物化性质

• 沸点：
  553.1±60.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  76.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-甲基哌嗪 、 11-(3-imino-5,6-dihydro-3H-benzo[h]cinnolin-2-yl)-undecanoic acid 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 11-(3-Imino-5,6-dihydrobenzo[h]cinnolin-2-yl)-1-(4-methylpiperazin-1-yl)undecan-1-one
  参考文献：
  名称：

  Discovery of a 3-Amino-6-phenyl-pyridazine Derivative as a New Synthetic Antineuroinflammatory Compound

  摘要：

  Excessive glial activation, with overproduction of cytokines and oxidative stress products, is detrimental and a hallmark of neurodegenerative disease pathology. Suppression of glial activation is a potential therapeutic approach, and protein kinases are targets of some antiinflammatory drugs. To address an unmet need for selective inhibitors of glial activation, we developed a novel 3-amino-6-phenylpyridazine derivative that selectively blocks increased IL-1beta, iNOS, and NO production by activated glia, without inhibition of potentially beneficial glial functions.

  DOI：

  10.1021/jm015573g
• 作为产物：
  描述：

  11-溴代十一烷酸乙酯 在 盐酸 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 11-(3-imino-5,6-dihydro-3H-benzo[h]cinnolin-2-yl)-undecanoic acid
  参考文献：
  名称：

  An aminopyridazine-based inhibitor of a pro-apoptotic protein kinase attenuates hypoxia-ischemia induced acute brain injury

  摘要：

  Death associated protein kinase (DAPK) is a calcium and calmodulin regulated enzyme that functions early in eukaryotic programmed cell death, or apoptosis. To validate DAPK as a potential drug discovery target for acute brain injury, the first small molecule DAPK inhibitor was synthesized and tested in vivo. A single injection of the aminopyridazine-based inhibitor administered 6 h after injury attenuated brain tissue or neuronal biomarker loss measured, respectively, 1 week and 3 days later. Because aminopyridazine is a privileged structure in neuropharmacology, we determined the high-resolution crystal structure of a binary complex between the kinase domain and a molecular fragment of the DAPK inhibitor. The co-crystal structure describes a structural basis for interaction and provides a firm foundation for structure-assisted design of lead compounds with appropriate molecular properties for future drug development.

  DOI：

  10.1016/s0960-894x(03)00733-9

文献信息

• Anti-Inflammatory And Protein Kinase Inhibitor Compositions And Related Methods For Downregulation Of Detrimental Cellular Responses And Inhibition Of Cell Death
  申请人：Watterson D.M.

  公开号：US20100317665A1

  公开（公告）日：2010-12-16

  A novel class of pyridazine compositions and related methods of use.
• US7888357B2
  申请人：——

  公开号：US7888357B2

  公开（公告）日：2011-02-15
• US8088774B2
  申请人：——

  公开号：US8088774B2

  公开（公告）日：2012-01-03
• Discovery of a 3-Amino-6-phenyl-pyridazine Derivative as a New Synthetic Antineuroinflammatory Compound
  作者：Salida Mirzoeva、Anu Sawkar、Magdalena Zasadzki、Ling Guo、Anastasia V. Velentza、Vincent Dunlap、Jean-Jacques Bourguignon、Helena Ramstrom、Jacques Haiech、Linda J. Van Eldik、D. Martin Watterson

  DOI：10.1021/jm015573g

  日期：2002.1.1

  Excessive glial activation, with overproduction of cytokines and oxidative stress products, is detrimental and a hallmark of neurodegenerative disease pathology. Suppression of glial activation is a potential therapeutic approach, and protein kinases are targets of some antiinflammatory drugs. To address an unmet need for selective inhibitors of glial activation, we developed a novel 3-amino-6-phenylpyridazine derivative that selectively blocks increased IL-1beta, iNOS, and NO production by activated glia, without inhibition of potentially beneficial glial functions.
• An aminopyridazine-based inhibitor of a pro-apoptotic protein kinase attenuates hypoxia-ischemia induced acute brain injury
  作者：Anastasia V. Velentza、Mark S. Wainwright、Magdalena Zasadzki、Salida Mirzoeva、Andrew M. Schumacher、Jacques Haiech、Pamela J. Focia、Martin Egli、D.Martin Watterson

  DOI：10.1016/s0960-894x(03)00733-9

  日期：2003.10

  Death associated protein kinase (DAPK) is a calcium and calmodulin regulated enzyme that functions early in eukaryotic programmed cell death, or apoptosis. To validate DAPK as a potential drug discovery target for acute brain injury, the first small molecule DAPK inhibitor was synthesized and tested in vivo. A single injection of the aminopyridazine-based inhibitor administered 6 h after injury attenuated brain tissue or neuronal biomarker loss measured, respectively, 1 week and 3 days later. Because aminopyridazine is a privileged structure in neuropharmacology, we determined the high-resolution crystal structure of a binary complex between the kinase domain and a molecular fragment of the DAPK inhibitor. The co-crystal structure describes a structural basis for interaction and provides a firm foundation for structure-assisted design of lead compounds with appropriate molecular properties for future drug development.