6-(3-methyl-2,6-dioxo-1-prop-2-ynyl-7H-purin-8-yl)naphthalene-2-carboxylic acid | 197076-01-0

• 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: 6-(3-methyl-2,6-dioxo-1-prop-2-ynyl-7H-purin-8-yl)naphthalene-2-carboxylic acid
• CAS: 197076-01-0
• 化学式: C₂₀H₁₄N₄O₄
• 分子量: 374.356
• InChiKey: RFROHBSGWZEOGQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-(3-methyl-2,6-dioxo-1-prop-2-ynyl-7H-purin-8-yl)naphthalene-2-carboxylic acid 、 碘甲烷 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以95%的产率得到6-(3,7-Dimethyl-2,6-dioxo-1-prop-2-ynyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-naphthalene-2-carboxylic acid methyl ester
  参考文献：
  名称：

  Configurationally stable analogs of styrylxanthines as A2A adenosine receptor antagonist

  摘要：

  Configurationally stable analogs of the potent, A(2A)-selective adenosine receptor (AR) antagonist 3,7-dimethyl-1-propargyl-8-styrylxanthine (8-styryl-DMPX, 3) were synthesized and investigated in radioligand binding assays for affinity to the high-affinity A(1)- and A(2A)-AR subtypes of rat brain. All derivatives prepared, including compounds in which the styryl double bond was replaced by a cyclopropane ring or a triple bond, or in which it was integrated into a (hetero) cyclic ring system, were less potent and less selective compared to the parent compound 3. The best compound of the present series was 8-(phenylethynyl)-DMPX (21), exhibiting a K-i value at A(2A)-AR of 300 nM and a > 10-fold selectivity versus A(1)-AR. In view of its configurational stability, 21 may be an interesting lead compound for the development of more potent A(2A) antagonists by introducing appropriate substituents in the phenyl ring. Based on conformational analysis of 8-styrylxanthine and 8-(2-naphthyl)xanthine derivatives, it is hypothesized that the bioactive conformation of (E)-8-styryl substituents with regard to the imidazole ring of the xanthine nucleus at A(2A)-AR may be nearly coplanar and cisoid, and may differ from the bioactive conformation of such xanthine derivatives at A(1)-AR.

  DOI：

  10.1016/s0223-5234(97)88913-1
• 作为产物：
  描述：

  6-(benzyloxycarbonyl)-2-naphthoic acid 在 吡啶 、 sodium hydroxide 、 氯化亚砜 、 potassium carbonate 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 53.25h， 生成 6-(3-methyl-2,6-dioxo-1-prop-2-ynyl-7H-purin-8-yl)naphthalene-2-carboxylic acid
  参考文献：
  名称：

  Configurationally stable analogs of styrylxanthines as A2A adenosine receptor antagonist

  摘要：

  Configurationally stable analogs of the potent, A(2A)-selective adenosine receptor (AR) antagonist 3,7-dimethyl-1-propargyl-8-styrylxanthine (8-styryl-DMPX, 3) were synthesized and investigated in radioligand binding assays for affinity to the high-affinity A(1)- and A(2A)-AR subtypes of rat brain. All derivatives prepared, including compounds in which the styryl double bond was replaced by a cyclopropane ring or a triple bond, or in which it was integrated into a (hetero) cyclic ring system, were less potent and less selective compared to the parent compound 3. The best compound of the present series was 8-(phenylethynyl)-DMPX (21), exhibiting a K-i value at A(2A)-AR of 300 nM and a > 10-fold selectivity versus A(1)-AR. In view of its configurational stability, 21 may be an interesting lead compound for the development of more potent A(2A) antagonists by introducing appropriate substituents in the phenyl ring. Based on conformational analysis of 8-styrylxanthine and 8-(2-naphthyl)xanthine derivatives, it is hypothesized that the bioactive conformation of (E)-8-styryl substituents with regard to the imidazole ring of the xanthine nucleus at A(2A)-AR may be nearly coplanar and cisoid, and may differ from the bioactive conformation of such xanthine derivatives at A(1)-AR.

  DOI：

  10.1016/s0223-5234(97)88913-1