5-amino-1-tert-butyl-4-<3-(2-furyl)-1,2,4-triazol-5-yl>pyrazole | 174648-67-0

• 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-amino-1-tert-butyl-4-<3-(2-furyl)-1,2,4-triazol-5-yl>pyrazole
• 英文别名: 2-tert-butyl-4-[5-(furan-2-yl)-1H-1,2,4-triazol-3-yl]pyrazol-3-amine
• CAS: 174648-67-0
• 化学式: C₁₃H₁₆N₆O
• 分子量: 272.31
• InChiKey: DMOPMYBMQYVXQV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  98.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-amino-1-tert-butyl-4-<3-(2-furyl)-1,2,4-triazol-5-yl>pyrazole 在 N-甲基吡咯烷酮 、 甲酸 、 对甲苯磺酸 作用下， 反应 4.0h， 生成 2-(furan-2-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine
  参考文献：
  名称：

  Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine Derivatives:  Potent and Selective A_2A Adenosine Antagonists

  摘要：

  A series of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine derivatives (10a-o,q,r), bearing alkyl and aralkyl chains on positions 7 and 8, were synthesized in the attempt to obtain potent and selective antagonists for the A(2A) adenosine receptor subtype. The compounds were tested in binding and functional assays to evaluate their potency for the A(2A) compared with the A(1) adenosine receptor subtype. In binding studies in rat brain membranes, most of the compounds showed affinity for A(2A) receptors in the low nanomolar range with a different degree of A(2A) versus A(1) selectivity. Comparison of N-7 (10a-d,h-o)- and N-8 (10e-g)-substituted pyrazolo derivatives indicates that N-7 substitution decreases the A(1) affinity with the concomitant increase of A(2A) selectivity. Specifically, the introduction of a 3-phenylpropyl group at pyrazolo nitrogen in position 7 (101) increased significantly the A(2A) selectivity, being 210-fold, while the A(2A) receptor affinity remained high (K-i = 2.4 nM). With regards to the affinity for A(2A) receptors, also the compound 10n, bearing in the 7-position a beta-morpholin-4-ylethyl group, deserves attention (K-i = 5.6 nM) even though the A(2A) selectivity (84-fold) was not as high as that of 101. Conversely, the compound 10m (N-7-4-phenylbutyl derivative) showed a remarkable selectivity (A(1)/A(2A) ratio = 129) associated with lower A(2A) affinity (K-i = 21 nM). In functional studies, most of the compounds examined reversed 5'-(N-ethylcarbamoyl)adenosine-induced inhibition of rabbit platelet aggregation inhibition which is a biological response mediated by the A(2A) receptor subtype. The compounds are potent and selective A(2A) antagonists which can be useful to elucidate the pathophysiological role of this adenosine receptor subtype. These compounds deserve to be further developed to assess their potential for treatment of neurodegenerative disorders such as Parkinson's disease.

  DOI：

  10.1021/jm950746l
• 作为产物：
  描述：

  5-氨基-4-氰基-1-叔丁基吡唑 在 盐酸 作用下， 以 二苯醚 、 乙二醇甲醚 为溶剂， 反应 12.5h， 生成 5-amino-1-tert-butyl-4-<3-(2-furyl)-1,2,4-triazol-5-yl>pyrazole
  参考文献：
  名称：

  Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine Derivatives:  Potent and Selective A_2A Adenosine Antagonists

  摘要：

  A series of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine derivatives (10a-o,q,r), bearing alkyl and aralkyl chains on positions 7 and 8, were synthesized in the attempt to obtain potent and selective antagonists for the A(2A) adenosine receptor subtype. The compounds were tested in binding and functional assays to evaluate their potency for the A(2A) compared with the A(1) adenosine receptor subtype. In binding studies in rat brain membranes, most of the compounds showed affinity for A(2A) receptors in the low nanomolar range with a different degree of A(2A) versus A(1) selectivity. Comparison of N-7 (10a-d,h-o)- and N-8 (10e-g)-substituted pyrazolo derivatives indicates that N-7 substitution decreases the A(1) affinity with the concomitant increase of A(2A) selectivity. Specifically, the introduction of a 3-phenylpropyl group at pyrazolo nitrogen in position 7 (101) increased significantly the A(2A) selectivity, being 210-fold, while the A(2A) receptor affinity remained high (K-i = 2.4 nM). With regards to the affinity for A(2A) receptors, also the compound 10n, bearing in the 7-position a beta-morpholin-4-ylethyl group, deserves attention (K-i = 5.6 nM) even though the A(2A) selectivity (84-fold) was not as high as that of 101. Conversely, the compound 10m (N-7-4-phenylbutyl derivative) showed a remarkable selectivity (A(1)/A(2A) ratio = 129) associated with lower A(2A) affinity (K-i = 21 nM). In functional studies, most of the compounds examined reversed 5'-(N-ethylcarbamoyl)adenosine-induced inhibition of rabbit platelet aggregation inhibition which is a biological response mediated by the A(2A) receptor subtype. The compounds are potent and selective A(2A) antagonists which can be useful to elucidate the pathophysiological role of this adenosine receptor subtype. These compounds deserve to be further developed to assess their potential for treatment of neurodegenerative disorders such as Parkinson's disease.

  DOI：

  10.1021/jm950746l

文献信息

• Pyrazolo[4,3-<i>e</i>]-1,2,4-triazolo[1,5-<i>c</i>]pyrimidine Derivatives:  Potent and Selective A_2A Adenosine Antagonists
  作者：Pier Giovanni Baraldi、Barbara Cacciari、Giampiero Spalluto、Maria José Pineda de las Infantas y Villatoro、Cristina Zocchi、Silvio Dionisotti、Ennio Ongini

  DOI：10.1021/jm950746l

  日期：1996.1.1

  A series of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine derivatives (10a-o,q,r), bearing alkyl and aralkyl chains on positions 7 and 8, were synthesized in the attempt to obtain potent and selective antagonists for the A(2A) adenosine receptor subtype. The compounds were tested in binding and functional assays to evaluate their potency for the A(2A) compared with the A(1) adenosine receptor subtype. In binding studies in rat brain membranes, most of the compounds showed affinity for A(2A) receptors in the low nanomolar range with a different degree of A(2A) versus A(1) selectivity. Comparison of N-7 (10a-d,h-o)- and N-8 (10e-g)-substituted pyrazolo derivatives indicates that N-7 substitution decreases the A(1) affinity with the concomitant increase of A(2A) selectivity. Specifically, the introduction of a 3-phenylpropyl group at pyrazolo nitrogen in position 7 (101) increased significantly the A(2A) selectivity, being 210-fold, while the A(2A) receptor affinity remained high (K-i = 2.4 nM). With regards to the affinity for A(2A) receptors, also the compound 10n, bearing in the 7-position a beta-morpholin-4-ylethyl group, deserves attention (K-i = 5.6 nM) even though the A(2A) selectivity (84-fold) was not as high as that of 101. Conversely, the compound 10m (N-7-4-phenylbutyl derivative) showed a remarkable selectivity (A(1)/A(2A) ratio = 129) associated with lower A(2A) affinity (K-i = 21 nM). In functional studies, most of the compounds examined reversed 5'-(N-ethylcarbamoyl)adenosine-induced inhibition of rabbit platelet aggregation inhibition which is a biological response mediated by the A(2A) receptor subtype. The compounds are potent and selective A(2A) antagonists which can be useful to elucidate the pathophysiological role of this adenosine receptor subtype. These compounds deserve to be further developed to assess their potential for treatment of neurodegenerative disorders such as Parkinson's disease.