5-(3-(octyloxy)benzyl)pyrimidine-2,4-diamine | 77113-60-1

• 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-(octyloxy)benzyl)pyrimidine-2,4-diamine
• 英文别名: 5-(3-Octyloxy-benzyl)-pyrimidine-2,4-diamine；5-[(3-octoxyphenyl)methyl]pyrimidine-2,4-diamine
• CAS: 77113-60-1
• 化学式: C₁₉H₂₈N₄O
• 分子量: 328.458
• InChiKey: RNZGHILIUCETNY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  24
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 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-(tetrahydro-2H-2-pyranyloxy)benzaldehyde 在 盐酸 、 氢氧化钾 、 sodium ethanolate 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 51.58h， 生成 5-(3-(octyloxy)benzyl)pyrimidine-2,4-diamine
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Inhibitors of Trypanosomal and Leishmanial Dihydrofolate Reductase

  摘要：

  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.

  DOI：

  10.1021/jm981130+

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.