5-(4-Ethoxy-benzyl)-pyrimidine-2,4-diamine

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-(4-Ethoxy-benzyl)-pyrimidine-2,4-diamine
• 英文别名: 5-[(4-ethoxyphenyl)methyl]pyrimidine-2,4-diamine
• 化学式: C₁₃H₁₆N₄O
• 分子量: 244.296
• InChiKey: BEACRNXDXGMHKJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  87
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(4-Ethoxy-benzyl)-pyrimidine-2,4-diamine 、 对甲苯磺酰氯 以50%的产率得到
  参考文献：
  名称：

  GRIGORYAN L. A.; KALDRIKYAN M. A.; TER-ZAXARYAN YU. Z.; PARONIKYAN R. V., ARM. XIM. ZH., 40,(1987) N 7, 443-447

  摘要：

  DOI：
• 作为产物：
  描述：

  4-乙氧基苯甲醛 在 sodium methylate 、 二甲基亚砜 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 生成 5-(4-Ethoxy-benzyl)-pyrimidine-2,4-diamine
  参考文献：
  名称：

  Immobilization of Malarial (Plasmodium falciparum) Dihydrofolate Reductase for the Selection of Tight-Binding Inhibitors from Combinatorial Library

  摘要：

  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。

  DOI：

  10.1021/ac070215s

文献信息

• 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.
• GRIGORYAN, L. A.;AKOPYAN, M. E.;KALDRIKYAN, M. A., ARM. XIM. ZH., 1983, 36, N 11, 722-726
  作者：GRIGORYAN, L. A.、AKOPYAN, M. E.、KALDRIKYAN, M. A.

  DOI：——

  日期：——
• 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。
• GRIGORYAN L. A.; KALDRIKYAN M. A.; TER-ZAXARYAN YU. Z.; PARONIKYAN R. V., ARM. XIM. ZH., 40,(1987) N 7, 443-447
  作者：GRIGORYAN L. A.、 KALDRIKYAN M. A.、 TER-ZAXARYAN YU. Z.、 PARONIKYAN R. V.

  DOI：——

  日期：——