Ethyl 11-(6-imino-3-phenylpyridazin-1(6H)-yl)undecanoate | 702683-11-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: Ethyl 11-(6-imino-3-phenylpyridazin-1(6H)-yl)undecanoate
• 英文别名: ethyl 11-(6-imino-3-phenylpyridazin-1-yl)undecanoate
• CAS: 702683-11-2
• 化学式: C₂₃H₃₃N₃O₂
• 分子量: 383.534
• InChiKey: INPIQGUFWNNYSH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  28
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  65.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Ethyl 11-(6-imino-3-phenylpyridazin-1(6H)-yl)undecanoate 在 盐酸 、 水 、 溶剂黄146 作用下， 反应 5.0h， 以95.2%的产率得到11-(6-imino-3-phenyl-6H-pyridazin-1-yl)-undecanoic acid
  参考文献：
  名称：

  Myosin light chain kinase inhibitor compounds, compostions and related methods of use

  摘要：

  吡啶并嗪类化合物、组合物及其相关使用方法。

  公开号：

  US20080021035A1
• 作为产物：
  描述：

  3-肼基-6-苯基吡嗪 在 镍 、 氢化铝 氢气 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 Ethyl 11-(6-imino-3-phenylpyridazin-1(6H)-yl)undecanoate
  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

文献信息

• Myosin light chain kinase inhibitor compounds, compostions and related methods of use
  申请人：Watterson M. D.

  公开号：US20080021035A1

  公开（公告）日：2008-01-24

  Pyridazinyl compounds, compositions and related methods of use.

  吡啶并嗪类化合物、组合物及其相关使用方法。
• 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.