ethyl 2,3,5,6-tetrahydro-3-oxobenzo[h]cinnoline-4-carboxylate | 183740-16-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: ethyl 2,3,5,6-tetrahydro-3-oxobenzo[h]cinnoline-4-carboxylate
• 英文别名: ethyl 3-oxo-5,6-dihydro-2H-benzo[h]cinnoline-4-carboxylate
• CAS: 183740-16-1
• 化学式: C₁₅H₁₄N₂O₃
• 分子量: 270.288
• InChiKey: KLCZRZWEZUNGRK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  67.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 2,3,5,6-tetrahydro-3-oxobenzo[h]cinnoline-4-carboxylate 在 三氯氧磷 作用下， 反应 2.0h， 以87%的产率得到ethyl 3-chloro-5,6-dihydrobenzo[h]cinnoline-4-carboxylate
  参考文献：
  名称：

  WO2006/50359

  摘要：

  公开号：
• 作为产物：
  描述：

  酮基丙二酸二乙酯 在 一水合肼 、 溶剂黄146 作用下， 反应 12.0h， 生成 ethyl 2,3,5,6-tetrahydro-3-oxobenzo[h]cinnoline-4-carboxylate
  参考文献：
  名称：

  Synthesis, Activity, and Molecular Modeling of a New Series of Tricyclic Pyridazinones as Selective Aldose Reductase Inhibitors

  摘要：

  Three new series of tricyclic pyridazinones have been synthesized and tested in vitro in order to assess (i) their ability to inhibit aldose reductase enzyme (ALR2) and (ii) their specificity toward the target enzyme with respect to other related oxidoreductases, such as aldehyde reductase, sorbitol dehydrogenase, and glutathione reductase. The inhibitory capability of the most effective compounds (IC50 values ranging from 6.44 to 12.6 mu M) appears to be associated with a rather significant specificity for ALR2. Molecular mechanics and molecular dynamic calculations performed on the ALR2-inhibitor complex give indications of specific interaction sites responsible for the binding, thus providing information for the design of new inhibitors with improved affinity for the enzyme.

  DOI：

  10.1021/jm960124f

文献信息

• 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。
• Structure-based design of an inhibitor modeled at the substrate active site of aldose reductase
  作者：Giulio Rastelli、Paola Vianello、Daniela Barlocco、Luca Costantino、Antonella Del Corso、Umberto Mura

  DOI：10.1016/s0960-894x(97)00321-1

  日期：1997.7

  This study presents the first successful example of structure-based drug design on aldose reductase in the extant literature. Starting from the structure of the modeled complex of aldose reductase with a pyridazinone acetic acid inhibitor that we previously disclosed, using the tools of molecular modeling for structure manipulation and molecular mechanics for energy minimization, we were able to design and synthesize a new analog that showed remarkably improved activity. We hope that a proper account of the most important enzyme-inhibitor interactions revealed by this study will allow, in the future, the design of new lead compounds having structures unrelated to carboxylic acids. (C) 1997 Elsevier Science Ltd.
• US8063047B2
  申请人：——

  公开号：US8063047B2

  公开（公告）日：2011-11-22
• Synthesis, Activity, and Molecular Modeling of a New Series of Tricyclic Pyridazinones as Selective Aldose Reductase Inhibitors
  作者：Luca Costantino、Giulio Rastelli、Katia Vescovini、Giorgio Cignarella、Paola Vianello、Antonella Del Corso、Mario Cappiello、Umberto Mura、Daniela Barlocco

  DOI：10.1021/jm960124f

  日期：1996.1.1

  Three new series of tricyclic pyridazinones have been synthesized and tested in vitro in order to assess (i) their ability to inhibit aldose reductase enzyme (ALR2) and (ii) their specificity toward the target enzyme with respect to other related oxidoreductases, such as aldehyde reductase, sorbitol dehydrogenase, and glutathione reductase. The inhibitory capability of the most effective compounds (IC50 values ranging from 6.44 to 12.6 mu M) appears to be associated with a rather significant specificity for ALR2. Molecular mechanics and molecular dynamic calculations performed on the ALR2-inhibitor complex give indications of specific interaction sites responsible for the binding, thus providing information for the design of new inhibitors with improved affinity for the enzyme.
• WO2006/50359
  申请人：——

  公开号：——

  公开（公告）日：——