(E)-N-(6-Amino-2,4-dioxo-3-prop-2-ynyl-1,2,3,4-tetrahydro-pyrimidin-5-yl)-3-benzo[1,3]dioxol-5-yl-acrylamide | 199680-82-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-N-(6-Amino-2,4-dioxo-3-prop-2-ynyl-1,2,3,4-tetrahydro-pyrimidin-5-yl)-3-benzo[1,3]dioxol-5-yl-acrylamide
• 英文别名: (E)-N-(6-amino-2,4-dioxo-3-prop-2-ynyl-1H-pyrimidin-5-yl)-3-(1,3-benzodioxol-5-yl)prop-2-enamide
• CAS: 199680-82-5
• 化学式: C₁₇H₁₄N₄O₅
• 分子量: 354.322
• InChiKey: YKYLGYRSUNLCHS-GQCTYLIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (E)-N-(6-Amino-2,4-dioxo-3-prop-2-ynyl-1,2,3,4-tetrahydro-pyrimidin-5-yl)-3-benzo[1,3]dioxol-5-yl-acrylamide 在 sodium hydroxide 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 8-((E)-2-Benzo[1,3]dioxol-5-yl-vinyl)-3-methyl-1-prop-2-ynyl-3,7-dihydro-purine-2,6-dione
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 3,7-Dimethyl-1-propargylxanthine Derivatives, A_2A-Selective Adenosine Receptor Antagonists

  摘要：

  A series of 8-substituted derivatives of 3,7-dimethyl-1-propargylxanthine (DMPX) was synthesized and investigated as A(2A) adenosine receptor antagonists. Different synthetic strategies for the preparation of DMPX derivatives and analogues were explored. A recently developed synthetic procedure starting from 3-propargyl-5,6-diaminouracil proved to be the method of choice for the preparation of this type of xanthine derivatives. The novel compounds were investigated in radioligand binding studies at the high-affinity adenosine receptor subtypes A(1) and A(2A) and compared with standard A(2A) adenosine receptor antagonists. Structure-activity relationships were analyzed in detail. 8-Styryl-substituted DMPX derivatives were identified that exhibit high affinity and selectivity for A(2A) adenosine receptors, including 8-(m-chlorostyryl)-DMPX (CS-DMPX, K-i A(2A) = 13 nM, 100-fold selective), 8-(m-bromostyryl)-DMPX (BS-DMPX, K-i A(2A) = 8 nM, 146-fold selective), and 8-(3,4-dimethoxystyryl)-DMPX (K-i A(2A) = 15 nM, 167-fold selective). These and other novel compounds are superior to the standard A(2A) adenosine receptor antagonists KF17837 (4) and CSC (5) with respect to A(2A) affinity and/or selectivity.

  DOI：

  10.1021/jm970515+
• 作为产物：
  描述：

  5,6-diamino-3-prop-2-ynyl-1H,3H-pyrimidine-2,4-dione 、 3,4-methylenedioxy-trans-cinnamic acid 在 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以71%的产率得到(E)-N-(6-Amino-2,4-dioxo-3-prop-2-ynyl-1,2,3,4-tetrahydro-pyrimidin-5-yl)-3-benzo[1,3]dioxol-5-yl-acrylamide
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 3,7-Dimethyl-1-propargylxanthine Derivatives, A_2A-Selective Adenosine Receptor Antagonists

  摘要：

  A series of 8-substituted derivatives of 3,7-dimethyl-1-propargylxanthine (DMPX) was synthesized and investigated as A(2A) adenosine receptor antagonists. Different synthetic strategies for the preparation of DMPX derivatives and analogues were explored. A recently developed synthetic procedure starting from 3-propargyl-5,6-diaminouracil proved to be the method of choice for the preparation of this type of xanthine derivatives. The novel compounds were investigated in radioligand binding studies at the high-affinity adenosine receptor subtypes A(1) and A(2A) and compared with standard A(2A) adenosine receptor antagonists. Structure-activity relationships were analyzed in detail. 8-Styryl-substituted DMPX derivatives were identified that exhibit high affinity and selectivity for A(2A) adenosine receptors, including 8-(m-chlorostyryl)-DMPX (CS-DMPX, K-i A(2A) = 13 nM, 100-fold selective), 8-(m-bromostyryl)-DMPX (BS-DMPX, K-i A(2A) = 8 nM, 146-fold selective), and 8-(3,4-dimethoxystyryl)-DMPX (K-i A(2A) = 15 nM, 167-fold selective). These and other novel compounds are superior to the standard A(2A) adenosine receptor antagonists KF17837 (4) and CSC (5) with respect to A(2A) affinity and/or selectivity.

  DOI：

  10.1021/jm970515+