5-[3-(4-hydroxyphenyl)propyl]-2-phenyl-2H-pyrazolo[4,3-d]pyrimidin-7-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-[3-(4-hydroxyphenyl)propyl]-2-phenyl-2H-pyrazolo[4,3-d]pyrimidin-7-amine
• 英文别名: 4-[3-(7-Amino-2-phenylpyrazolo[4,3-d]pyrimidin-5-yl)propyl]phenol；4-[3-(7-amino-2-phenylpyrazolo[4,3-d]pyrimidin-5-yl)propyl]phenol
• 化学式: C₂₀H₁₉N₅O
• 分子量: 345.404
• InChiKey: OOMFSONRFBINNP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  89.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-[3-(4-hydroxyphenyl)propyl]-2-phenyl-2H-pyrazolo[4,3-d]pyrimidin-7-amine 、 3-氯丙烯 在 caesium carbonate 作用下， 以 甲醇 为溶剂， 反应 0.67h， 以49%的产率得到5-[3-(4-allyloxyphenyl)propyl]-2-phenyl-2H-pyrazolo[4,3-d]pyrimidin-7-amine
  参考文献：
  名称：

  7-Amino-2-phenylpyrazolo[4,3-d]pyrimidine derivatives: Structural investigations at the 5-position to target human A1 and A2A adenosine receptors. Molecular modeling and pharmacological studies

  摘要：

  In previous research, several 7-amino-2-arylpyrazolo[4,3-d]pyrimidine derivatives were identified as highly potent and selective antagonists at the human A3 adenosine receptor. Structure-activity relationship studies highlighted that affinity and selectivity depended on the nature of the substituents at the 5- and 7-positions of the pyrazolo[4,3-d]pyrimidine scaffold. In particular, small lipophilic residues at the 5-position and a free amino group at position 7 afforded compounds able to bind all four human (h) adenosine receptors. Hence, to shift affinity toward the hA1 and/or hA(2A) subtypes, alkyl and arylalkyl chains of different length were appended at position 5 of the 2-phenylpyrazolo[4,3-d]pyrimidin-7-amine. Among the new compounds, a dual hA1/hA(2A) receptor antagonist was identified, namely the 5-(3-phenylpropyl) derivative 25, which shows high affinity both at human A1 (K(i) = 5.31 nM) and A(2A) (K(i) = 55 nM) receptors. We also obtained some potent and selective antagonists for the A1 receptor, such as the 5-(3-arylpropyl)-substituted compounds 26-31, whose affinities fall in the low nanomolar range (K(i) = 0.15-18 nM). Through an in silico receptor-driven approach, the obtained binding data were rationalized and the molecular bases of the hA1 and hA(2A) AR affinity and selectivity of derivatives 25-31 are explained.

  DOI：

  10.1016/j.ejmech.2014.07.060
• 作为产物：
  描述：

  4-(4-甲氧基苯基)丁腈 在 盐酸 、 ammonium acetate 、 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 48.17h， 生成 5-[3-(4-hydroxyphenyl)propyl]-2-phenyl-2H-pyrazolo[4,3-d]pyrimidin-7-amine
  参考文献：
  名称：

  7-Amino-2-phenylpyrazolo[4,3-d]pyrimidine derivatives: Structural investigations at the 5-position to target human A1 and A2A adenosine receptors. Molecular modeling and pharmacological studies

  摘要：

  In previous research, several 7-amino-2-arylpyrazolo[4,3-d]pyrimidine derivatives were identified as highly potent and selective antagonists at the human A3 adenosine receptor. Structure-activity relationship studies highlighted that affinity and selectivity depended on the nature of the substituents at the 5- and 7-positions of the pyrazolo[4,3-d]pyrimidine scaffold. In particular, small lipophilic residues at the 5-position and a free amino group at position 7 afforded compounds able to bind all four human (h) adenosine receptors. Hence, to shift affinity toward the hA1 and/or hA(2A) subtypes, alkyl and arylalkyl chains of different length were appended at position 5 of the 2-phenylpyrazolo[4,3-d]pyrimidin-7-amine. Among the new compounds, a dual hA1/hA(2A) receptor antagonist was identified, namely the 5-(3-phenylpropyl) derivative 25, which shows high affinity both at human A1 (K(i) = 5.31 nM) and A(2A) (K(i) = 55 nM) receptors. We also obtained some potent and selective antagonists for the A1 receptor, such as the 5-(3-arylpropyl)-substituted compounds 26-31, whose affinities fall in the low nanomolar range (K(i) = 0.15-18 nM). Through an in silico receptor-driven approach, the obtained binding data were rationalized and the molecular bases of the hA1 and hA(2A) AR affinity and selectivity of derivatives 25-31 are explained.

  DOI：

  10.1016/j.ejmech.2014.07.060