2-Amino-4-cyclohexyl-6-(4-dimethylamino-phenyl)-nicotinonitrile | 328527-00-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-Amino-4-cyclohexyl-6-(4-dimethylamino-phenyl)-nicotinonitrile
• CAS: 328527-00-0
• 化学式: C₂₀H₂₄N₄
• 分子量: 320.437
• InChiKey: DVJHHCRUVQHIFW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.32
• 重原子数：
  24.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  65.94
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-Amino-4-cyclohexyl-6-(4-dimethylamino-phenyl)-nicotinonitrile 在 氨 、 对甲苯磺酸 作用下， 生成 2-((Z)-2-Amino-vinylamino)-4-cyclohexyl-6-(4-dimethylamino-phenyl)-nicotinonitrile
  参考文献：
  名称：

  Structure–activity studies of 5-substituted pyridopyrimidines as adenosine kinase inhibitors

  摘要：

  The synthesis and SAR of a novel series of non-nucleoside pyridopyrimidine inhibitors of the enzyme adenosine kinase (AK) are described. It was found that pyridopyrimidines with a broad range of medium and large non-polar substituents at the 5-position potently inhibited AK activity. A narrower range of analogues was capable of potently inhibiting adenosine phosphorylation in intact cells indicating an enhanced ability of these analogues to penetrate cell membranes. Potent AK inhibitors were found to effectively reduce nociception in animal models of thermal hyperalgesia and persistent pain. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00602-8
• 作为产物：
  描述：

  4-chlorobenzoylmethylenetriphenylphosphorane 在 ammonium acetate 作用下， 以 二甲基亚砜 、 1,2-二氯乙烷 、 甲苯 为溶剂， 生成 2-Amino-4-cyclohexyl-6-(4-dimethylamino-phenyl)-nicotinonitrile
  参考文献：
  名称：

  Structure–activity studies of 5-substituted pyridopyrimidines as adenosine kinase inhibitors

  摘要：

  The synthesis and SAR of a novel series of non-nucleoside pyridopyrimidine inhibitors of the enzyme adenosine kinase (AK) are described. It was found that pyridopyrimidines with a broad range of medium and large non-polar substituents at the 5-position potently inhibited AK activity. A narrower range of analogues was capable of potently inhibiting adenosine phosphorylation in intact cells indicating an enhanced ability of these analogues to penetrate cell membranes. Potent AK inhibitors were found to effectively reduce nociception in animal models of thermal hyperalgesia and persistent pain. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00602-8

文献信息

• Discovery of 4-Amino-5-(3-bromophenyl)-7-(6-morpholino-pyridin- 3-yl)pyrido[2,3-<i>d</i>]pyrimidine, an Orally Active, Non-Nucleoside Adenosine Kinase Inhibitor
  作者：Chih-Hung Lee、Meiqun Jiang、Marlon Cowart、Greg Gfesser、Richard Perner、Ki Hwan Kim、Yu Gui Gu、Michael Williams、Michael F. Jarvis、Elizabeth A. Kowaluk、Andrew O. Stewart、Shripad S. Bhagwat

  DOI：10.1021/jm000314x

  日期：2001.6.1

  Adenosine (ADO) is an endogenous homeostatic inhibitory neuromodulator that reduces cellular excitability at sites of tissue injury and inflammation, inhibition of adenosine kinase (AK), the primary metabolic enzyme for ADO, selectively increases ADO concentrations at sites of tissue trauma and enhances the analgesic and antiinflammatory actions of ADO. Optimization of the high-throughput screening lead, 4-amino-7-aryl-substituted pteridine (5) (AK IC50 = 440 nM), led to the identification of compound 21 (4-amino-5-(3-bromophenyl)-7-(6-morpholino- pyridin-3-yl)pyrido [2,3-d]pyrimidine, ABT-702), a novel, potent (AK IC50 = 1.7 nM) non-nucleoside AK inhibitor with oral. activity in animal models of pain and inflammation.