4-methyl-2H-pyrazole-3-carbaldehyde | 1284220-50-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-methyl-2H-pyrazole-3-carbaldehyde
• 英文别名: 4-methyl-1H-pyrazole-5-carbaldehyde
• CAS: 1284220-50-3
• 化学式: C₅H₆N₂O
• mdl: MFCD12548027
• 分子量: 110.115
• InChiKey: MHLFPJZIBXEVSD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  45.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-Chloroquinoline-4-carbaldehyde[3-(cyclopropylmethyl)-1-methyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl]hydrazone 、 4-methyl-2H-pyrazole-3-carbaldehyde 在 哌啶 作用下， 生成 2-[(6-chloroquinolin-4-yl)methyl]-7-(cyclopropylmethyl)-5-methyl-3-(4-methyl-1H-pyrazol-5-yl)pyrazolo[3,4-d]pyrimidine-4,6-dione
  参考文献：
  名称：

  Design of inhibitors of Helicobacter pylori glutamate racemase as selective antibacterial agents: Incorporation of imidazoles onto a core pyrazolopyrimidinedione scaffold to improve bioavailabilty

  摘要：

  Structure-activity relationships are presented around a series of pyrazolopyrimidinediones that inhibit the growth of Helicobacter pylori by targeting glutamate racemase, an enzyme that provides d-glutamate for the construction of N-acetylglucosamine-N-acetylmuramic acid peptidoglycan subunits assimilated into the bacterial cell wall. Substituents on the inhibitor scaffold were varied to optimize target potency, antibacterial activity and in vivo pharmacokinetic stability. By incorporating an imidazole ring at the 7-position of scaffold, high target potency was achieved due to a hydrogen bonding network that occurs between the 3-position nitrogen atom, a bridging water molecule and the side chains Ser152 and Trp244 of the enzyme. The lipophilicity of the scaffold series proved important for expression of antibacterial activity. Clearances in vitro and in vivo were monitored to identify compounds with improved plasma stability. The basicity of the imidazole may contribute to increased aqueous solubility at lower pH allowing for improved oral bioavailability.

  DOI：

  10.1016/j.bmcl.2012.07.004

文献信息

• [BMIM]BF₄ Mediated Multi-component Synthesis of Phenyl-4-(1Hpyrazol- 5-yl)-1H-pyrazolo[3,4-b]quinolin-5(4H)-ones and Evaluation of their Anti-cancer Activity
  作者：A. Srinivas、A.J. Shree、S.S.K. Goud

  DOI：10.2174/1570178620666230831162320

  日期：2024.2

  Pyrazolo bridged quinolones scaffolds are an important building block in many of the medicinally active new chemical entities. In the current work, synthesis of phenyl-4-(1H-pyrazol-5-yl) conjugated with 1H-pyrazolo[3,4-b]quinolin-5(4H)-ones derivatives has been achieved by one-pot threecomponent reaction of 3-methyl-1-phenyl-1H-pyrazol-5-amine 1, 5,5-dimethylcyclohexane-1,3-diones 2, and 1H-pyrazole-5-carbaldehydes

  吡唑并桥喹诺酮支架是许多具有药物活性的新化学实体的重要组成部分。本工作通过一锅三组分反应实现了苯基-4-(1H-吡唑-5-基)与1H-吡唑并[3,4-b]喹啉-5(4H)-酮衍生物的合成。使用 [BMIM]BF4 作为绿色反应介质，合成 3-甲基-1-苯基-1H-吡唑-5-胺 1、5,5-二甲基环己烷-1,3-二酮 2 和 1H-吡唑-5-甲醛 3良好的产量。此外，还评估了合成化合物对 HeLa 和 DU145 细胞的细胞毒性潜力。在八种衍生物中，化合物 4d 对 DU145 和 HeLa 细胞表现出良好的细胞毒性，IC50 值分别为 8.5 和 8.9 μM。分子对接研究表明，化合物4d对人检查点激酶1表现出良好的结合能（-8.4 kcal/mol）。
• [BMIM][OH]-Mediated One-Pot Synthesis of 2-Amino-5-oxo-4-(1H-pyrazol-5-yl)-5H-chromeno[4,3-b]pyridine-3-carbonitriles as Potential Anticancer Agents
  作者：A. Srinivas、A. Jaya Shree、S. Sharath Kumar Goud

  DOI：10.1134/s1070363223010279

  日期：2023.1
• [BMIM]BF4-Mediated One-Pot Synthesis of 6-Amino-5-{(4-hydroxy-2-oxo-2H-chromen-3-yl)[1H-pyrazol-5(4)-yl]­methyl}-1,3-dimethylpyrimidine-2,4(1H,3H)-diones
  作者：K. Maram、K. Anitha、R. Sreenivasulu、R. R. Raju

  DOI：10.1134/s1070428023030168

  日期：2023.3
• Synthesis, Anticancer Activity and Molecular Docking Studies of Pyrazole Conjugated Pthalazine-2-carbonitriles
  作者：K. Kalpana、V. Anitha Rani、P. Yedla、S. Hussain Mohammed

  DOI：10.1134/s1070363223080170

  日期：2023.8
• Design of inhibitors of Helicobacter pylori glutamate racemase as selective antibacterial agents: Incorporation of imidazoles onto a core pyrazolopyrimidinedione scaffold to improve bioavailabilty
  作者：Gregory S. Basarab、Pamela Hill、Charles J. Eyermann、Madhu Gowravaram、Helena Käck、Ekundayo Osimoni

  DOI：10.1016/j.bmcl.2012.07.004

  日期：2012.9

  Structure-activity relationships are presented around a series of pyrazolopyrimidinediones that inhibit the growth of Helicobacter pylori by targeting glutamate racemase, an enzyme that provides d-glutamate for the construction of N-acetylglucosamine-N-acetylmuramic acid peptidoglycan subunits assimilated into the bacterial cell wall. Substituents on the inhibitor scaffold were varied to optimize target potency, antibacterial activity and in vivo pharmacokinetic stability. By incorporating an imidazole ring at the 7-position of scaffold, high target potency was achieved due to a hydrogen bonding network that occurs between the 3-position nitrogen atom, a bridging water molecule and the side chains Ser152 and Trp244 of the enzyme. The lipophilicity of the scaffold series proved important for expression of antibacterial activity. Clearances in vitro and in vivo were monitored to identify compounds with improved plasma stability. The basicity of the imidazole may contribute to increased aqueous solubility at lower pH allowing for improved oral bioavailability.