8-((E)-2-Benzo[1,3]dioxol-5-yl-vinyl)-3-methyl-1-prop-2-ynyl-3,7-dihydro-purine-2,6-dione | 199680-92-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 8-((E)-2-Benzo[1,3]dioxol-5-yl-vinyl)-3-methyl-1-prop-2-ynyl-3,7-dihydro-purine-2,6-dione
• 英文别名: 8-[(E)-2-(1,3-benzodioxol-5-yl)ethenyl]-3-methyl-1-prop-2-ynyl-7H-purine-2,6-dione
• CAS: 199680-92-7
• 化学式: C₁₈H₁₄N₄O₄
• 分子量: 350.334
• InChiKey: ADESTIQKKYKDKN-FNORWQNLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  87.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  8-((E)-2-Benzo[1,3]dioxol-5-yl-vinyl)-3-methyl-1-prop-2-ynyl-3,7-dihydro-purine-2,6-dione 、 碘甲烷 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以74%的产率得到8-((E)-2-Benzo[1,3]dioxol-5-yl-vinyl)-3,7-dimethyl-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：

  3,4-methylenedioxy-trans-cinnamic acid 在 sodium hydroxide 、 potassium carbonate 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 51.0h， 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+

文献信息

• Synthesis and Structure−Activity Relationships of 3,7-Dimethyl-1-propargylxanthine Derivatives, A_2A-Selective Adenosine Receptor Antagonists
  作者：Christa E. Müller、Uli Geis、Jo Hipp、Ulrike Schobert、Wolfram Frobenius、Maciej Pawłowski、Fumio Suzuki、Jesús Sandoval-Ramírez

  DOI：10.1021/jm970515+

  日期：1997.12.1

  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.