1-(3-phenylpropyl)-4-cyano-5-aminopyrazole | 174648-50-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(3-phenylpropyl)-4-cyano-5-aminopyrazole
• 英文别名: 5-amino-4-cyano-1-(3-phenylpropyl)pyrazole；5-Amino-1-(3-phenylpropyl)pyrazole-4-carbonitrile
• CAS: 174648-50-1
• 化学式: C₁₃H₁₄N₄
• 分子量: 226.281
• InChiKey: LLUBBDJPBNHNGK-UHFFFAOYSA-N

物化性质

• 沸点：
  450.3±40.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  67.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(3-phenylpropyl)-4-cyano-5-aminopyrazole 在 N-甲基吡咯烷酮 、 盐酸 、 对甲苯磺酸 作用下， 以 二苯醚 、 乙二醇甲醚 为溶剂， 反应 12.5h， 生成 Sch 63390
  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：

  乙氧基亚甲基丙二腈 、 (3-苯基丙基)-肼 以 乙醇 为溶剂， 反应 18.0h， 以72%的产率得到1-(3-phenylpropyl)-4-cyano-5-aminopyrazole
  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

• Organoruthenium Antagonists of Human A₃Adenosine Receptors
  作者：Priyankar Paira、Mun Juinn Chow、Gopalakrishnan Venkatesan、Vamsi Krishna Kosaraju、Siew Lee Cheong、Karl-Norbert Klotz、Wee Han Ang、Giorgia Pastorin

  DOI：10.1002/chem.201203291

  日期：2013.6.17

  triazolo moiety with an organoruthenium fragment. The objective was to introduce by design structural diversity into the PTP scaffold in order to tune their binding efficacy toward the target receptor. These novel organoruthenium antagonists displayed good aquatic stability and moderate binding affinity toward the hA3 receptor in the low micromolar range. The assembly of these complexes through a template‐driven

  人A 3腺苷受体（hA 3 AR）是膜结合的G蛋白偶联受体，与许多严重的病理状况（包括癌症）有关，在其中它可能成为潜在的治疗靶标。为了推导基于吡唑并三唑并嘧啶（PTP）的A 3 AR拮抗剂的构效关系，我们通过用有机钌片段代替三唑并开发了新型的有机金属抑制剂。目的是通过设计将结构多样性引入PTP支架中，以调节其对靶受体的结合功效。这些新型的有机钌拮抗剂显示出良好的水生稳定性和对hA 3的中等结合亲和力受体在低微摩尔范围内。讨论了通过模板驱动的方法组装这些复合物，并在金属中心进行选择性配体置换以控制其空间和受体结合特性的方法。
• Antimicrobial and antitumor activity of n-heteroimmine-1,2,3-dithiazoles and their transformation in triazolo-, imidazo-, and pyrazolopirimidines
  作者：Pier Giovanni Baraldi、Maria Giovanna Pavani、Maria del Carmen Nuñez、Patrizia Brigidi、Beatrice Vitali、Roberto Gambari、Romeo Romagnoli

  DOI：10.1016/s0968-0896(01)00294-2

  日期：2002.2

  sodium methoxide in refluxing methanol. This provides a general and attractive route to 4-methoxy-6-cyano pyrazolo[3,4-d]pyrimidines from 1-substituted 5-amino pyrazoles 10-19 in two simple steps. Finally, the isosteric replacement of the pyrazole ring atoms to give the imidazole[3,4-d]pyrimidine and triazole [4,5-d] pyrimidine ring systems was examined.

  Appel盐与邻氨基腈杂环10-19的反应得到相应的4-氯-5-杂亚胺-1,2,3-二噻唑20-29，对其抗菌，抗真菌和抗肿瘤活性进行了评估。尽管所有这些N-杂亚胺都没有显着的抗菌活性，但它们显示出显着的抗真菌活性。而且，相同的衍生物代表了杂环合成中的通用中间体，实际上，吡唑亚氨基二噻唑20-26可以一步转化为相应的4-甲氧基-吡唑并[3,4-d]嘧啶30-的2-氰基衍生物。 35由甲醇钠在甲醇中回流。这提供了通过两个简单的步骤从1-取代的5-氨基吡唑10-19生成4-甲氧基-6-氰基吡唑并[3,4-d]嘧啶的一般且有吸引力的途径。最后，
• 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.