2-amino-8-nicotinoyl-4-phenyl-5H-indeno[1,2-d]pyrimidin-5-one | 1356002-59-9

• 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: 2-amino-8-nicotinoyl-4-phenyl-5H-indeno[1,2-d]pyrimidin-5-one
• 英文别名: 2-Amino-4-phenyl-8-(pyridine-3-carbonyl)indeno[1,2-d]pyrimidin-5-one
• CAS: 1356002-59-9
• 化学式: C₂₃H₁₄N₄O₂
• 分子量: 378.39
• InChiKey: WMZRGJNFVYCBOW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  98.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-amino-8-nicotinoyl-4-phenyl-5H-indeno[1,2-d]pyrimidin-5-one 在 二乙胺基三氟化硫 作用下， 反应 4.0h， 以23%的产率得到2-amino-8-(difluoro(pyridin-3-yl)methyl)-4-phenyl-5H-indeno-[1,2-d]pyrimidin-5-one
  参考文献：
  名称：

  Design and Characterization of Optimized Adenosine A_2A/A₁ Receptor Antagonists for the Treatment of Parkinson's Disease

  摘要：

  The design and characterization of two, dual adenosine A(2A)/A(1) receptor antagonists in several animal models of Parkinson's disease is described. Compound 1 was previously reported as a potential treatment for Parkinson's disease. Further characterization of 1 revealed that it was metabolized to reactive intermediates that caused the genotoxicity of 1 in the Ames and mouse lymphoma L51784 assays. The identification of the metabolites enabled the preparation of two optimized compounds 13 and 14 that were devoid of the metabolic liabilities associated with 1. Compounds 13 and 14 are potent dual A(2A)/A(1) receptor antagonists that have excellent activity, after oral administration, across a number of animal models of Parkinson's disease including mouse and rat models of haloperidol-induced catalepsy, mouse and rat models of reserpine-induced akinesia, and the rat 6-hydroxydopamine (6-OHDA) lesion model of drug-induced rotation.

  DOI：

  10.1021/jm201640m
• 作为产物：
  描述：

  tert-butyl N-(8-methyl-5-oxo-4-phenylindeno[1,2-d]pyrimidin-2-yl)-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamate 在 N-甲基吡咯烷酮 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 N-溴代丁二酰亚胺(NBS) 、 邻苯二甲酸二丁酯 、 potassium carbonate 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 水 、 苯 为溶剂， 反应 18.17h， 生成 2-amino-8-nicotinoyl-4-phenyl-5H-indeno[1,2-d]pyrimidin-5-one
  参考文献：
  名称：

  Design and Characterization of Optimized Adenosine A_2A/A₁ Receptor Antagonists for the Treatment of Parkinson's Disease

  摘要：

  The design and characterization of two, dual adenosine A(2A)/A(1) receptor antagonists in several animal models of Parkinson's disease is described. Compound 1 was previously reported as a potential treatment for Parkinson's disease. Further characterization of 1 revealed that it was metabolized to reactive intermediates that caused the genotoxicity of 1 in the Ames and mouse lymphoma L51784 assays. The identification of the metabolites enabled the preparation of two optimized compounds 13 and 14 that were devoid of the metabolic liabilities associated with 1. Compounds 13 and 14 are potent dual A(2A)/A(1) receptor antagonists that have excellent activity, after oral administration, across a number of animal models of Parkinson's disease including mouse and rat models of haloperidol-induced catalepsy, mouse and rat models of reserpine-induced akinesia, and the rat 6-hydroxydopamine (6-OHDA) lesion model of drug-induced rotation.

  DOI：

  10.1021/jm201640m