2-氨基-4-羟基-6-甲基-5-炔丙基嘧啶 | 81887-01-6

• 物质功能分类: 医药中间体 - 杂环化合物 - 嘧啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 2-氨基-4-羟基-6-甲基-5-炔丙基嘧啶
• 中文别名: 2-氨基-6-甲基-5-(2-丙炔)-4(1H)-嘧啶酮
• 英文名称: 2-Amino-6-methyl-5-(2-propynyl)-4(1H)-pyrimidinone
• 英文别名: 2-amino-6-methyl-5-(2-propynyl)-4(3H)-pyrimidinone；2-amino-6-methyl-5-(prop-2-yn-1-yl)pyrimidin-4(3H)-one；4-Methyl-6-hydroxy-5-(2-propynyl)-2-pyrimidinamine；2-amino-4-methyl-5-prop-2-ynyl-1H-pyrimidin-6-one
• CAS: 81887-01-6
• 化学式: C₈H₉N₃O
• mdl: MFCD09746372
• 分子量: 163.179
• InChiKey: JXNPWSZLCOTXSA-UHFFFAOYSA-N

物化性质

• 沸点：
  295.1±42.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  67.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-氨基-4-羟基-6-甲基-5-炔丙基嘧啶 在 potassium carbonate 、 氯乙酸 、 三氯氧磷 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 43.0h， 生成 2,4-Dichloro-6-methyl-5-(2-propynyl)pyrimidine
  参考文献：
  名称：

  2,4-Dichloro-5-(1-o-carboranylmethyl)-6-methylpyrimidine: a potential synthon for 5-(1-o-carboranylmethyl)pyrimidines

  摘要：

  The synthesis of 2,4-dichloro-5-(1-o-carboranylmethyl)-6-methylpyrimidine is described. Synthetically, this novel o-carboranyl pyrimidine is approached from ethyl 2-acetyl-4-pentynoate through alkylation of ethyl acetoacetate with propargyl bromide and subsequent condensation with thiourea to yield 6-methyl-5-(2-propynyl)-2-thio-4(1H,3H)-pyrimidinone. Hydrolysis of the 2-thione and chlorination with POCl3 gives 2,4-dichloro-6-methyl-5(2-propynyl)pyrimidine. Gentle refluxing of this product with B10H14/CH3CN in toluene yields the target, 2,4-dichloro-5-(1-o-carboranylmethyl)-6-methylpyrimidine, a potential synthon for a variety of 2,4-substituted 5-(1-o-carboranylmethyl)-6-methylpyrimidines and/or the corresponding nido-undecaborates.

  DOI：

  10.1021/jo00007a026
• 作为产物：
  描述：

  ethyl 2-acetylpent-4-ynoate 、 碳酸胍 以 二甲基亚砜 、 丙酮 为溶剂， 生成 2-氨基-4-羟基-6-甲基-5-炔丙基嘧啶
  参考文献：
  名称：

  Herbicidal sulfonamides

  摘要：

  这项发明涉及一种新型的芳基磺酰脲基呋[2,3-d]嘧啶类化合物，例如N'-[(4,6-二甲基呋[2,3-d]嘧啶-2-基)氨基甲酰]-N,N-二甲基苯-1,2-磺酰胺，以及它们作为除草剂和植物生长调节剂的用途。这些新型化合物可以通过将适当的呋[2,3-d]嘧啶-2-胺与适当取代的芳基磺酰异氰酸酯或异硫氰酸酯反应而制备。

  公开号：

  US04487626A1

文献信息

• Herbicidal sulfonamides
  申请人：E. I. Du Pont de Nemours and Company

  公开号：US04487626A1

  公开（公告）日：1984-12-11

  This invention relates to a novel class of arylsulfonylureidofuro[2,3-d]pyrimidines, such as N'-[(4,6-dimethylfuro[2,3-d]pyrimidin-2-yl)aminocarbonyl]-N,N-dimethylbenz ene-1,2-sulfonamide, and their use as herbicides and plant growth regulants. These novel compounds can be prepared by reacting an appropriate furo[2,3-d]pyrimidin-2-amine with an appropriately substituted arylsulfonyl isocyanate or isothiocyanate.

  这项发明涉及一种新型的芳基磺酰脲基呋[2,3-d]嘧啶类化合物，例如N'-[(4,6-二甲基呋[2,3-d]嘧啶-2-基)氨基甲酰]-N,N-二甲基苯-1,2-磺酰胺，以及它们作为除草剂和植物生长调节剂的用途。这些新型化合物可以通过将适当的呋[2,3-d]嘧啶-2-胺与适当取代的芳基磺酰异氰酸酯或异硫氰酸酯反应而制备。
• Assay Development and Identification of the First Plasmodium falciparum 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase Inhibitors
  作者：Marie Hoarau、Nattida Suwanakitti、Thaveechai Varatthan、Ratthiya Thiabma、Roonglawan Rattanajak、Netnapa Charoensetakul、Emily K. Redman、Tanatorn Khotavivattana、Tirayut Vilaivan、Yongyuth Yuthavong、Sumalee Kamchonwongpaisan

  DOI：10.3390/molecules27113515

  日期：——

  In the fight towards eradication of malaria, identifying compounds active against new drug targets constitutes a key approach. Plasmodium falciparum 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase (PfHPPK) has been advanced as a promising target, as being part of the parasite essential folate biosynthesis pathway while having no orthologue in the human genome. However, no drug discovery efforts have been reported on this enzyme. In this study, we conducted a three-step screening of our in-house antifolate library against PfHPPK using a newly designed PfHPPK-GFP protein construct. Combining virtual screening, differential scanning fluorimetry and enzymatic assay, we identified 14 compounds active against PfHPPK. Compounds’ binding modes were investigated by molecular docking, suggesting competitive binding with the HMDP substrate. Cytotoxicity and in vitro ADME properties of hit compounds were also assessed, showing good metabolic stability and low toxicity. The most active compounds displayed low micromolar IC50 against drug-resistant parasites. The reported hit compounds constitute a good starting point for inhibitor development against PfHPPK, as an alternative approach to tackle the malaria parasite.

  在消灭疟疾的斗争中，识别对新药物靶点活性的化合物构成了一个关键的方法。疟原虫7,8-二氢-6-羟甲基-4-对氨基苯磷酸酰基化酶（PfHPPK）已被提出作为一个有前途的靶点，因为它是疟原虫必需的叶酸生物合成途径的一部分，而在人类基因组中没有同源物。然而，目前尚未有关于这种酶的药物发现工作的报道。在本研究中，我们使用新设计的PfHPPK-GFP蛋白构建物对我们自己的抗叶酸类药物库进行了三步筛选，以针对PfHPPK进行筛选。结合虚拟筛选、差异扫描荧光法和酶活性测定，我们鉴定出了14种对PfHPPK活性的化合物。通过分子对接研究了化合物的结合模式，表明它们与HMDP底物竞争结合。还评估了命中化合物的细胞毒性和体外ADME特性，显示出良好的代谢稳定性和低毒性。最活跃的化合物对耐药疟原虫显示出低微摩尔级别的IC50。报道的命中化合物构成了针对PfHPPK的抑制剂开发的良好起点，作为一种替代方法来对抗疟原虫。
• US4487626A
  申请人：——

  公开号：US4487626A

  公开（公告）日：1984-12-11
• 2,4-Dichloro-5-(1-o-carboranylmethyl)-6-methylpyrimidine: a potential synthon for 5-(1-o-carboranylmethyl)pyrimidines
  作者：Robert C. Reynolds、Todd W. Trask、W. David Sedwick

  DOI：10.1021/jo00007a026

  日期：1991.3

  The synthesis of 2,4-dichloro-5-(1-o-carboranylmethyl)-6-methylpyrimidine is described. Synthetically, this novel o-carboranyl pyrimidine is approached from ethyl 2-acetyl-4-pentynoate through alkylation of ethyl acetoacetate with propargyl bromide and subsequent condensation with thiourea to yield 6-methyl-5-(2-propynyl)-2-thio-4(1H,3H)-pyrimidinone. Hydrolysis of the 2-thione and chlorination with POCl3 gives 2,4-dichloro-6-methyl-5(2-propynyl)pyrimidine. Gentle refluxing of this product with B10H14/CH3CN in toluene yields the target, 2,4-dichloro-5-(1-o-carboranylmethyl)-6-methylpyrimidine, a potential synthon for a variety of 2,4-substituted 5-(1-o-carboranylmethyl)-6-methylpyrimidines and/or the corresponding nido-undecaborates.