6-(3-methoxyphenyl)-2-phenyl-1,2,4-triazolo[4,3-a]pyrazine-3,8-(2H,7H)-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 6-(3-methoxyphenyl)-2-phenyl-1,2,4-triazolo[4,3-a]pyrazine-3,8-(2H,7H)-dione
• 英文别名: 6-(3-methoxyphenyl)-2-phenyl-7H-[1,2,4]triazolo[4,3-a]pyrazine-3,8-dione
• 化学式: C₁₈H₁₄N₄O₃
• 分子量: 334.334
• InChiKey: ACMJTJLHQAQHCS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  74.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(3-methoxyphenyl)-2-phenyl-1,2,4-triazolo[4,3-a]pyrazine-3,8-(2H,7H)-dione 在 氨 、 三溴化硼 、 potassium carbonate 、 三氯氧磷 作用下， 以 乙醇 、 二氯甲烷 、 丁酮 为溶剂， 反应 16.5h， 生成 8-amino-6-(3-benzyloxyphenyl)-2-phenyl-1,2,4-triazolo[4,3-a]-pyrazin-3(2H)-one
  参考文献：
  名称：

  The 1,2,4-Triazolo[4,3-a]pyrazin-3-one as a Versatile Scaffold for the Design of Potent Adenosine Human Receptor Antagonists. Structural Investigations to Target the A_2A Receptor Subtype

  摘要：

  In this work, we describe the identification of the 1,2,4-triazolo[4,3-a]pyrazin-3-one as a new versatile scaffold for the development of adenosine human (h) receptor antagonists. The new chemotype ensued from a molecular simplification approach applied to our previously reported 1,2,4-triazolo[4,3-a]quinoxalin-1-one series. Hence, a set of novel 8-amino-2-aryl-1,2,4-triazolopyrazin-3-one derivatives, featured by different substituents on the 2-phenyl ring (R) and at position 6 (R-6), was synthesized with the main purpose of targeting the hA(2A) adenosine receptor (AR). Several compounds possessed nanomolar affinity for the hA(2A) AR (K-i = 2.910 nM) and some, very interestingly, also showed high selectivity for the target. One selected potent hA(2A) AR antagonist (12, R = H, R-6 = 4-methoxyphenyl) demonstrated some ability to counteract MPP+-induced neurotoxicity in cultured human neuroblastoma SH-SY5Y cells, a widely used in vitro Parkinsons disease model. Docking studies at hAR structures were performed to rationalize the observed affinity data.

  DOI：

  10.1021/acs.jmedchem.7b00457
• 作为产物：
  描述：

  ethyl (phenylhydrazono)chloroacetate 在 ammonium acetate 、 氨 、 potassium carbonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 5.75h， 生成 6-(3-methoxyphenyl)-2-phenyl-1,2,4-triazolo[4,3-a]pyrazine-3,8-(2H,7H)-dione
  参考文献：
  名称：

  The 1,2,4-Triazolo[4,3-a]pyrazin-3-one as a Versatile Scaffold for the Design of Potent Adenosine Human Receptor Antagonists. Structural Investigations to Target the A_2A Receptor Subtype

  摘要：

  In this work, we describe the identification of the 1,2,4-triazolo[4,3-a]pyrazin-3-one as a new versatile scaffold for the development of adenosine human (h) receptor antagonists. The new chemotype ensued from a molecular simplification approach applied to our previously reported 1,2,4-triazolo[4,3-a]quinoxalin-1-one series. Hence, a set of novel 8-amino-2-aryl-1,2,4-triazolopyrazin-3-one derivatives, featured by different substituents on the 2-phenyl ring (R) and at position 6 (R-6), was synthesized with the main purpose of targeting the hA(2A) adenosine receptor (AR). Several compounds possessed nanomolar affinity for the hA(2A) AR (K-i = 2.910 nM) and some, very interestingly, also showed high selectivity for the target. One selected potent hA(2A) AR antagonist (12, R = H, R-6 = 4-methoxyphenyl) demonstrated some ability to counteract MPP+-induced neurotoxicity in cultured human neuroblastoma SH-SY5Y cells, a widely used in vitro Parkinsons disease model. Docking studies at hAR structures were performed to rationalize the observed affinity data.

  DOI：

  10.1021/acs.jmedchem.7b00457