3,5-diamino-4-(4-methoxybenzyl)-1H-pyrazole | 163590-19-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3,5-diamino-4-(4-methoxybenzyl)-1H-pyrazole
• 英文别名: 4-(4-methoxybenzyl)-1H-pyrazole-3,5-diamine；4-[(4-methoxyphenyl)methyl]-1H-pyrazole-3,5-diamine
• CAS: 163590-19-0
• 化学式: C₁₁H₁₄N₄O
• mdl: MFCD00265986
• 分子量: 218.258
• InChiKey: KPHPMNHOOYVICO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  90
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,5-diamino-4-(4-methoxybenzyl)-1H-pyrazole 在 乙醇 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 乙醇 为溶剂， 反应 144.0h， 生成 6-cyano-2,7-diamino-3-(4-methoxybenzyl)-5-(4-methoxyphenyl)pyrazolo<1,5-a>pyrimidine
  参考文献：
  名称：

  Ram, Vishnu J.; Nath, Mahendra, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1995, vol. 34, # 5, p. 416 - 422

  摘要：

  DOI：
• 作为产物：
  描述：

  2-(4-甲氧基苄基)丙二腈 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 8.0h， 以25%的产率得到3,5-diamino-4-(4-methoxybenzyl)-1H-pyrazole
  参考文献：
  名称：

  Ram, Vishnu J.; Nath, Mahendra; Chandra, Subhash, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1994, vol. 33, # 11, p. 1048 - 1052

  摘要：

  DOI：

文献信息

• Three-component regioselective synthesis and antibacterial evaluation of new arene-linked bis(pyrazolo[1,5-<i>a</i>]pyrimidine) hybrids
  作者：Sherif M. H. Sanad、Ahmed E. M. Mekky

  DOI：10.1080/00397911.2023.2191854

  日期：——

  synthesize butane-linked bis(pyrazolo[1,5-a]pyrimidines) 1 attached to arene units in 74–81% yields. The one-pot reaction involved reacting bis(aldehyde) with the respective 1H-pyrazole-3,5-diamines and acetophenones in ethanol at 80 °C in the presence of potassium hydroxide for 6 h. Using a similar protocol, another series of regioisomeric bis(pyrazolo[1,5-a]pyrimidines) 2 was prepared, in 77–87% yields

  摘要 在当前的研究中，采用三组分方案以 74-81% 的收率高效合成丁烷连接的双（吡唑并 [1,5- a ] 嘧啶）1连接到芳烃单元。一锅法反应涉及双（醛）与各自的 1 H-吡唑-3,5-二胺和苯乙酮在乙醇中于 80 °C 在氢氧化钾存在下反应 6 小时。使用类似的方案，另一系列的区域异构双（吡唑并[1,5- a ]嘧啶）2以 77-87% 的产率制备，利用适当的合成子双（乙酰基）和苯甲醛。新产品对六种不同的 ATCC 菌株表现出广泛的抗菌活性。一般而言，连接到 3-(4-甲氧基苄基) 单元的产品的抗菌活性超过其连接到 3-(4-氯苄基) 单元的类似物。此外，与具有对电子释放取代基的芳烃单元连接的杂化物表现出改善的抗菌活性。杂化的2h、3-(4-甲氧基苄基)和 7-(4-甲氧基苯基)单元对所有测试菌株具有最佳抗菌活性。它表现出比环丙沙星更有效的活性，MIC/MBC 值高达 2.0/4.0 µM。
• Three‐component synthesis of arene‐linked pyrazolo[1,5‐<i>a</i>]pyrimidines
  作者：Ahmed A. M. Ahmed、Ahmed E. M. Mekky、Sherif M. H. Sanad

  DOI：10.1002/jhet.4688

  日期：2023.10

  In this study, we aimed to establish an efficient method for synthesizing two new series of arene-linked pyrazolo[1,5-a]pyrimidines. This was achieved by reacting 1H-pyrazole-3,5-diamines with the respective acetophenones and benzaldehydes in a 1:1:1 ratio. To optimize this three-component reaction, various bases, and solvents were investigated. Use of two equivalents of KOH in ethanol at reflux for

  在本研究中，我们的目的是建立一种有效的方法来合成两个新系列的芳烃连接的吡唑并[1,5- a ]嘧啶。这是通过将 1 H-吡唑-3,5-二胺与相应的苯乙酮和苯甲醛以 1:1:1 的比例反应来实现的。为了优化这种三组分反应，研究了各种碱和溶剂。使用两当量的 KOH 在乙醇中回流 4-6 小时，可获得 89%-96% 的所需产物产率。通过考虑新产品的元素和光谱数据，阐明了新产品的结构。
• Synthesis of New Bis(pyrazolo[1,5‐<i>a</i>]pyrimidines) Linked to Different Spacers as Potential MurB Inhibitors
  作者：Sherif M. H. Sanad、Alshimaa A. M. Abdelsalam、Aya A. Gamal Eldin、Esraa H. Abdelfattah、Fatma R. M. Hussein、Nada G. Mohammed、Nariman A. S. Taha、Ahmed E. M. Mekky

  DOI：10.1002/cbdv.202300546

  日期：2023.6

  efficient protocol was adopted to efficiently prepare three new series of bis(pyrazolo[1,5-a]pyrimidines) linked to different spacers. The new bis(pyrazolo[1,5-a]pyrimidines) were prepared in 80–90 % yields by reacting the respective bis(enaminones) and 4-(4-substituted benzyl)-1H-pyrazole-3,5-diamines in pyridine at reflux temperature for 5–7 h. The new products showed a wide spectrum of antibacterial activity

  采用有效的方案有效地制备了连接到不同间隔基的三个新系列的双(吡唑并[1,5- a ]嘧啶)。通过使相应的双(烯胺酮)和4-(4-取代的苄基)-1 H-吡唑-3,5-二胺反应，制备了新的双(吡唑并[1,5- a ]嘧啶)，产率为80-90%在吡啶中回流5-7小时。新产品对六种不同的细菌菌株表现出广泛的抗菌活性。一般来说，丙烷和丁烷连接的双(吡唑并[1,5- a]嘧啶），连接到3-（4-甲基-或4-甲氧基苄基）单位，具有最好的抗菌活性，最低抑菌浓度（MIC）和最低杀菌浓度（MBC）值分别高达2.5和5.1 μM 。此外，之前的产品表现出良好的 MurB 抑制活性，IC 50值高达 7.2 μM。
• Discovery of mixed type thymidine phosphorylase inhibitors endowed with antiangiogenic properties: Synthesis, pharmacological evaluation and molecular docking study of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones. Part II
  作者：Hriday Bera、Probir kumar Ojha、Bee Jen Tan、Lingyi Sun、Anton V. Dolzhenko、Wai-Keung Chui、Gigi Ngar Chee Chiu

  DOI：10.1016/j.ejmech.2014.03.063

  日期：2014.5

  In our drug discovery program, a series of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones were designed, synthesized and evaluated for their TP inhibitory potential. All the synthesized analogues conferred a varying degree of TP inhibitory activity, comparable or better than positive control, 7-deazaxanthine (7-DX, 2) (IC50 value = 42.63 mu M). A systematic approach to the lead optimization identified compounds 3c and 4a as the most promising TP inhibitors, exhibiting mixed mode of enzyme inhibition. Moreover, selected compounds demonstrated the ability to attenuate the expression of the angiogenic markers (viz. MMP-9 and VEGF) in MDA-MB-231 cells at sublethal concentrations. In addition, molecular docking studies revealed the plausible binding orientation of these inhibitors towards TP, which was in accordance with the experimental results. Taken as a whole, these compounds would constitute a new direction for the design of novel TP inhibitors with promising antiangiogenic properties. (C) 2014 Elsevier Masson SAS. All rights reserved.
• The Synthesis of Some Derivatives Based on the 4-Benzyl-1H-pyrazole-3,5-diamine Core
  作者：Petr Cankař、Lukáš Jedinák、Vladimír Kryštof

  DOI：10.3987/com-10-12101

  日期：——

  The three-step synthesis of 4-benzyl-1H-pyrazole-3,5-diamines 2 from commercially available aldehydes 3 is given. The Knoevenagel condensation was utilized to assemble the initial carbon framework, resulting in the benzylidenemalononitriles 4 which were directly transformed by the reduction of the electron deficient C=C bond to benzylmalononitriles 5. Subsequent cycloaddition of hydrazine with 5 afforded the desired pyrazoles 2. Due to the high similarity with 4-arylazo-1H-pyrazole-3,5-diamines, the biological activities of the 4-benzyl-1H-pyrazole-3,5-diamines 2 were evaluated while focusing on the inhibition of cyclin-dependent kinases (CDKs), but no significant results were obtained.