5-(3-Butoxy-benzyl)-pyrimidine-2,4-diamine | 77113-63-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-(3-Butoxy-benzyl)-pyrimidine-2,4-diamine
• 英文别名: 5-[(3-butoxyphenyl)methyl]pyrimidine-2,4-diamine
• CAS: 77113-63-4
• 化学式: C₁₅H₂₀N₄O
• 分子量: 272.35
• InChiKey: WHVMKGLHPRGZHK-UHFFFAOYSA-N

物化性质

• 熔点：
  166.6-168.3 °C
• 沸点：
  508.8±60.0 °C(Predicted)
• 密度：
  1.167±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  87
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-丁氧基苯甲醛 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 55.0h， 生成 5-(3-Butoxy-benzyl)-pyrimidine-2,4-diamine
  参考文献：
  名称：

  定量结构-选择性关系。比较5-（取代的苄基）-2,4-二氨基嘧啶对大肠杆菌和牛肝二氢叶酸还原酶的抑制作用。

  摘要：

  在我们以前的出版物中（Blaney，JM； Dietrich，SW； Reynolds，MA； Hansch，CJ Med。Chem。1979，22，614），提出了相关方程式对牛肝和大肠杆菌二氢叶酸还原酶（DHFR）的抑制作用。 5-（取代的苄基）-2,4-二氨基嘧啶。这些方程式揭示了这两种酶与取代基相互作用的方式的差异，这解释了甲氧苄啶等药物的高选择性。我们在本报告中测试并进一步开发了这些方程式。特别令人感兴趣的是，我们先前发布的大肠杆菌DHFR相关方程可准确预测目前在临床上使用的甲氧苄氨嘧啶（tetroxoprim）的商业竞争者的效力。我们认为，可以通过两个相关方程设计甲氧苄啶的新的有效竞争者。

  DOI：

  10.1021/jm00137a012

文献信息

• Quantitative structure-selectivity relationships. Comparison of the inhibition of Escherichia coli and bovine liver dihydrofolate reductase by 5-(substituted-benzyl)-2,4-diaminopyrimidines
  作者：Ren-Li Li、Stephen W. Dietrich、Corwin Hansch

  DOI：10.1021/jm00137a012

  日期：1981.5

  In our previous publication (Blaney, J. M.; Dietrich, S. W.; Reynolds, M. A.; Hansch, C. J. Med. Chem. 1979, 22, 614), correlation equations were presented for the inhibition of bovine liver and Escherichia coli dihydrofolate reductase (DHFR) by 5-(substituted benzyl)-2,4-diaminopyrimidines. These equations brought out differences in the way these two enzymes interact with substituents, which explain

  在我们以前的出版物中（Blaney，JM； Dietrich，SW； Reynolds，MA； Hansch，CJ Med。Chem。1979，22，614），提出了相关方程式对牛肝和大肠杆菌二氢叶酸还原酶（DHFR）的抑制作用。 5-（取代的苄基）-2,4-二氨基嘧啶。这些方程式揭示了这两种酶与取代基相互作用的方式的差异，这解释了甲氧苄啶等药物的高选择性。我们在本报告中测试并进一步开发了这些方程式。特别令人感兴趣的是，我们先前发布的大肠杆菌DHFR相关方程可准确预测目前在临床上使用的甲氧苄氨嘧啶（tetroxoprim）的商业竞争者的效力。我们认为，可以通过两个相关方程设计甲氧苄啶的新的有效竞争者。
• Design, Synthesis, and Evaluation of Inhibitors of Trypanosomal and Leishmanial Dihydrofolate Reductase
  作者：Shafinaz F. Chowdhury、Victor Bernier Villamor、Ramon Hurtado Guerrero、Isabel Leal、Reto Brun、Simon L. Croft、Jonathan M. Goodman、Louis Maes、Luis M. Ruiz-Perez、Dolores Gonzalez Pacanowska、Ian H. Gilbert

  DOI：10.1021/jm981130+

  日期：1999.10.1

  This paper concerns the design, synthesis, and evaluation of inhibitors of leishmanial and trypanosomal dihydrofolate reductase. Initially study was made of the structures of the leishmanial and human enzyme active sites to see if there were significant differences which could be exploited for selective drug design. Then a series of compounds were synthesized based on 5-benzyl-2,4-diaminopyrimidines. These compounds were assayed against the protozoan and human enzymes and showed selectivity for the protozoan enzymes. The structural data was then used to rationalize the enzyme assay data. Compounds were also tested against the clinically relevant forms of the intact parasite. Activity was seen against the trypanosomes for a number of compounds. The compounds were in general less active against Leishmania. This latter result may be due to uptake problems. Two of the compounds also showed some in vivo activity in a model of African trypanosomiasis.
• Immobilization of Malarial (<i>Plasmodium falciparum</i>) Dihydrofolate Reductase for the Selection of Tight-Binding Inhibitors from Combinatorial Library
  作者：Chawanee Thongpanchang、Supannee Taweechai、Sumalee Kamchonwongpaisan、Yongyuth Yuthavong、Yodhathai Thebtaranonth

  DOI：10.1021/ac070215s

  日期：2007.7.1

  A simple procedure for selection of tight-binding inhibitors of mutant dihydrofolate reductases from Plasmodium falciparum (PfDHFRs) based on preferential binding to the enzyme immobilized on a Sepharose column has been described. PfDHFRs with a cysteine residue at the C-terminal have been prepared in order to immobilize to a thiopropyl-Sepharose gel via S−S linkage. The amount of immobilized DHFRs was estimated to be 4−5 mg/g of dried gel, and the activities of bound DHFRs were comparable to that of free enzymes. The prepared immobilized enzyme has been used for the selection of tight-binding inhibitors from combinatorial libraries, based on the affinities of each ligand with the enzyme. Free ligands were then identified and analyzed quantitatively by high-performance liquid chromatography−mass spectrometry, and the components with high binding affinity of the library could thus be realized. Results could be confirmed by quantitative analysis of the bound ligands released from the enzyme by guanidine hydrochloride treatment.

  已经描述了一种基于优先结合固定在Sepharose柱上的酶的选择突变型恶性疟原虫二氢叶酸还原酶（PfDHFRs）的紧密结合抑制剂的简单程序。为了通过S-S键固定到硫丙基-Sepharose凝胶上，制备了在C末端具有半胱氨酸残基的PfDHFRs。估计固定化的DHFRs量为4-5毫克/克干燥凝胶，并且与自由酶的活性相当。制备的固定化酶已被用于从组合库中选择紧密结合抑制剂，基于每个配体与酶的亲和力。然后通过高效液相色谱-质谱法识别和定量分析自由配体，从而实现库中具有高结合亲和力的成分。结果可以通过定量分析通过盐酸胍处理从酶中释放的结合配体来确认。