5,6-二氢-苯并并[h]肉啉-3-胺 | 627529-41-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 5,6-二氢-苯并并[h]肉啉-3-胺
• 英文名称: 5,6-dihydro-benzo[h]cinnolin-3-ylamine
• 英文别名: 5,6-dihydrobenzo[h]cinnolin-3-amine
• CAS: 627529-41-3
• 化学式: C₁₂H₁₁N₃
• 分子量: 197.239
• InChiKey: QKVREUJWFZJEJK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  51.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5,6-二氢-苯并并[h]肉啉-3-胺 在 盐酸 、 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 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 39.0h， 生成 11-(3-Imino-5,6-dihydro-3H-benzo[h]cinnolin-2-yl)-1-(4-pyrimidin-2-yl-piperazin-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：

  3-hydrazino-5,6-dihydrobenzocinnoline 在 镍 氢气 作用下， 以 甲醇 为溶剂， 反应 4.0h， 生成 5,6-二氢-苯并并[h]肉啉-3-胺
  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

• Heterocyclic Bis-Cations as Starting Hits for Design of Inhibitors of the Bifunctional Enzyme Histidine-Containing Protein Kinase/Phosphatase from <i>Bacillus</i> <i>s</i><i>ubtilis</i>
  作者：Helena Ramström、Maryline Bourotte、Claude Philippe、Martine Schmitt、Jacques Haiech、Jean-Jacques Bourguignon

  DOI：10.1021/jm021043o

  日期：2004.4.1

  phosphorylation of HPr (histidine-containing protein) at Ser-46 by the ATP-dependent HPr kinase, which in Bacillus subtilis, Lactobacillus casei, and Staphylococcus xylosus also exhibits phosphatase activity and is thus a bifunctional enzyme (HPrK/P). Since deficiency of HPrK/P in S. xylosus, L. casei, and B. subtilis mutants leads to severe growth defects, inhibitors of the enzyme could form a new family of antibiotic

  在低鸟嘌呤和低胞嘧啶革兰氏阳性细菌中碳分解代谢物阻遏/激活的主要机制似乎涉及到ATP依赖性HPr激酶在Ser-46处HPr（含组氨酸的蛋白）的磷酸化，该酶在枯草芽孢杆菌中，干酪乳杆菌和木糖葡萄球菌也具有磷酸酶活性，因此是一种双功能酶（HPrK / P）。由于木糖链球菌，干酪乳杆菌和枯草芽孢杆菌突变体中HPrK / P的缺乏会导致严重的生长缺陷，因此该酶的抑制剂可能会形成一个新的抗生素药物家族。这项研究的目的是筛选一个内部化学文库，以鉴定作为枯草芽孢杆菌中HPrK / P抑制剂的命中物，并使用放射性体外测定法从命中优化中进一步提取结构特征的其他信息。对称的双阳离子化合物LPS 02-10-L-D09（2a）具有桥接两个2-氨基苯并咪唑部分的12个碳原子的烷基连接基，被确定为具有10 microM的EC（50）值的非ATP模拟化合物在以HPr为底物的激酶测定中 该物质还抑制了添加无机磷酸盐后触发的HPrK
• PYRIDAZINE COMPOUNDS AND METHODS
  申请人：Watterson Martin

  公开号：US20090029985A1

  公开（公告）日：2009-01-29

  The invention relates to novel chemical compounds, compositions and methods of making and using the same. In particular, the invention provides pyridazine compounds and/or related heterocyclic derivatives, compositions comprising the same, and methods of using pyridazine compounds and/or related heterocyclic derivatives and compositions comprising the same, for modulation of cellular pathways (e.g., signal transduction pathways), for treatment or prevention of inflammatory diseases (e.g., Alzheimer's disease), for research, drug screening, and therapeutic applications.

  本发明涉及新型化学化合物、组合物及其制备和使用的方法。具体而言，本发明提供了吡嗪化合物和/或相关的杂环衍生物，包括这些化合物的组合物，以及使用吡嗪化合物和/或相关的杂环衍生物和组合物的方法，用于调节细胞通路（例如信号转导通路），用于治疗或预防炎症性疾病（例如阿尔茨海默氏病），用于研究、药物筛选和治疗应用。
• Advanced drug development and manufacturing
  申请人：Los Alamos National Security, LLC

  公开号：EP2511844A2

  公开（公告）日：2012-10-17

  There is described an apparatus for measuring protein characteristics comprising an X-ray fluorescence (XRF) spectrometer comprising a source of polychromatic X-rays, an X-ray detector, a protein, a molecule that has been exposed to and at least weakly binds to the protein, a plurality of X-ray fluorescence signal data obtained by irradiating chemical elements in the protein and molecule with the polychromatic X-rays and a security system for maintaining records for the data from the plurality of X-ray fluorescence signal measurements. There is also described an x-ray microscope for measuring a sample.

  描述了一种测量蛋白质特性的仪器，该仪器包括一个 X 射线荧光 (XRF) 光谱仪，其中包括一个多色 X 射线源、一个 X 射线探测器、一个蛋白质、一个已暴露于该蛋白质并至少与该蛋白质弱结合的分子、通过用多色 X 射线照射蛋白质和分子中的化学元素而获得的多个 X 射线荧光信号数据，以及一个用于维护多个 X 射线荧光信号测量数据记录的安全系统。此外，还介绍了一种用于测量样品的 X 射线显微镜。
• 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.
• ADVANCED DRUG DEVELOPMENT AND MANUFACTURING
  申请人：Los Alamos National Security, LLC

  公开号：EP2084519A2

  公开（公告）日：2009-08-05