2,4-diamino-5-(4-hydroxybenzyl)pyrimidine | 30077-67-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2,4-diamino-5-(4-hydroxybenzyl)pyrimidine
• 英文别名: 2,4-Diamino-5-<4-hydroxy-benzyl>pyrimidin；4-(2,4-diamino-pyrimidin-5-ylmethyl)-phenol；Phenol, 4-[(2,4-diamino-5-pyrimidinyl)methyl]-；4-[(2,4-diaminopyrimidin-5-yl)methyl]phenol
• CAS: 30077-67-9
• 化学式: C₁₁H₁₂N₄O
• 分子量: 216.242
• InChiKey: CEFCYXFPPQNRCK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  98
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,4-diamino-5-(4-hydroxybenzyl)pyrimidine 在 potassium tert-butylate 作用下， 以 二甲基亚砜 为溶剂， 反应 2.5h， 生成 2,4-diamino-5-[3-allyl-4-(allyloxy)benzyl]pyrimidine
  参考文献：
  名称：

  2,4-Diamino-5-benzylpyrimidines as antibacterial agents. 13. Some alkenyl derivatives with high in vitro activity against anaerobic organisms

  摘要：

  A series of 2,4-diamino-5-(3,5-dialkenyl-4-methoxy- or -4-hydroxybenzyl)pyrimidines was prepared from [(allyloxy)benzyl]pyrimidines by Claisen rearrangements, and the resulting allyl phenols were further modified by methylation and rearrangement to 1-propenyl analogues. Analogous 3,4-dimethoxy-5-alkenyl derivatives were prepared by similar techniques. High in vitro antibacterial activity was obtained against certain anaerobic organisms, such as Bacteroides species and Fusobacterium, which was equal to or better than the control, metronidazole, in several cases. The profile was similar against Neisseria gonorrhoeae and Staphylococcus aureus. The 3,5-bis(1-propenyl)-4-methoxy derivative 8 was 1 order of magnitude more active against Escherichia coli dihydrofolate reductase than its saturated counterpart, and it was also more active than trimethoprim, 1. However, it was considerably less active in vitro against the Gram-negative organisms. The 3,4-dimethoxy-5-alkenyl, -5-alkyl, and -5-alkoxy analogues had very high broad-spectrum antibacterial activity. However, pharmacokinetic studies of four of the compounds in dogs and rats and in vivo studies with an abdominal sepsis model in rats showed no advantages over trimethoprim.

  DOI：

  10.1021/jm00128a043
• 作为产物：
  描述：

  4-苄氧基苯甲醛 在 palladium on activated charcoal 氢气 、 sodium methylate 、 溶剂黄146 作用下， 以 甲醇 、 乙醇 、 二甲基亚砜 为溶剂， 85.0~100.0 ℃ 、310.27 kPa 条件下， 反应 2.25h， 生成 2,4-diamino-5-(4-hydroxybenzyl)pyrimidine
  参考文献：
  名称：

  2,4-Diamino-5-benzylpyrimidines as antibacterial agents. 7. Analysis of the effect of 3,5-dialkyl substituent size and shape on binding to four different dihydrofolate reductase enzymes

  摘要：

  A group of trimethoprim (TMP) analogues containing 3,5-dialkyl(or halo)-4-alkoxy, -hydroxy, or -amino substitution were analyzed in terms of their inhibitory activities against four dihydrofolate reductase (DHFR) isozymes. Although selectivities were lower than with TMP, the activities against vertebrate DHFR were usually at least 2 orders of magnitude less than against enzymes from microbial sources. However, the profiles of activity were remarkably similar for rat, Neisseria gonorrhoeae, and Plasmodium berghei enzymes in all three series, although somewhat different for Escherichia coli DHFR, leading to the conclusion that the hydrophobic pockets are similar for the first three isozymes. Optimal substitution was reached with 3,5-di-n-propyl or 3-ethyl-5-n-propyl groups. Branching of chains at the alpha-carbon, which resulted in increased substituent thickness, was detrimental to E. coli DHFR inhibition in particular. MR is an inadequate parameter for use in correlating such substituent effects. Conformational changes of the more bulky inhibitors can be invoked to explain some differences in inhibitory pattern. Although log P explains simple substituent effects with the vertebrate DHFRs very well, it is insufficient in the more complex cases described here, where shape is clearly involved as well. Solvent-accessible surface areas were measured for TMP in E. coli and chicken DHFRs, where the coordinates are now known. The environment is more hydrophobic in the latter case; this can also be postulated for rat DHFR, which has a very similar activity profile. As with the mammalian isozymes, N. gonorrhoeae DHFR contains an active site phenylalanine replacing Leu-28 of E. coli DHFR, thus creating a more hydrophobic pocket. A similar replacement may also occur in the P.berghei isozyme. Selectivity for bacterial DHFR is dependent on the nature of the 4-substituent, being low for polar 4-hydroxy compounds but high for polar 4-amino analogues, possibly as a result of solvation differences. With complex substituents, the environment of each atom in the active site must be taken into account to adequately explain structure-activity relationships.

  DOI：

  10.1021/jm00385a017

文献信息

• 2,4-Diaminopyrimidines as inhibitors of Leishmanial and Trypanosomal dihydrofolate reductase
  作者：Didier Pez、Isabel Leal、Fabio Zuccotto、Cyrille Boussard、Reto Brun、Simon L Croft、Vanessa Yardley、Luis M Ruiz Perez、Dolores Gonzalez Pacanowska、Ian H Gilbert

  DOI：10.1016/j.bmc.2003.08.012

  日期：2003.11

  selective inhibitors of leishmanial and trypanosomal dihydrofolate reductase. Compounds were then assayed against the recombinant parasite and human enzymes. Some of the compounds showed good activity. They were also tested against the intact parasites using in vitro assays. Good activity was found against Trypanosoma cruzi, moderate activity against Trypanosoma brucei and Leishmania donovani. Molecular

  本文描述了4'-取代和3'，4'-二取代的5-苄基-2,4-二氨基嘧啶作为利什曼体和锥虫二氢叶酸还原酶的选择性抑制剂的合成。然后针对重组寄生虫和人类酶测定化合物。一些化合物显示出良好的活性。还使用体外测定法针对完整的寄生虫对它们进行了测试。发现对克鲁斯锥虫的活性良好，对布鲁氏锥虫和多形利什曼原虫的活性中等。进行分子建模以解释结果。发现利什曼酶比活性酶在活性位点具有更广泛的亲脂结合区。结合在口袋中的化合物显示出最高的选择性。
• HEAT-RESISTANT ADHESIVES AND SEMICONDUCTOR DEVICES PRODUCED THEREWITH
  申请人：Hitachi Chemical Company, Ltd.

  公开号：EP0984051A1

  公开（公告）日：2000-03-08

  A thermoresistance adhesive which does not dissolve in the sealer-composing resins at the sealer molding temperature and is capable of providing a semiconductor chip/lead frame adhesive strength under shear of 1 N/4 mm2 or greater, and including, for example, amide, imide, ester or ether linkage is suited for use in producing thermoresistance adhesive solutions and thermoresistance resin pastes, and the semiconductor chips, lead frames, films, etc., made by using such an adhesive are suited for providing low-cost semiconductor devices.

  在封口机成型温度下不溶解于封口机组成树脂中，并能在 1 N/4 mm2 或更大剪切力下提供半导体芯片/引线框架粘合强度的耐热粘合剂，例如包括酰胺、亚胺、酯或醚连接，适合用于生产耐热粘合剂溶液和耐热树脂浆料，使用这种粘合剂制造的半导体芯片、引线框架、薄膜等适合用于提供低成本半导体器件。
• ROTH, BARBARA;TIDWELL, MARY Y.;FERONE, ROBERT;BACCANAR, DAVID P.;SIGEL, C+, J. MED. CHEM., 32,(1989) N, C. 1949-1958
  作者：ROTH, BARBARA、TIDWELL, MARY Y.、FERONE, ROBERT、BACCANAR, DAVID P.、SIGEL, C+

  DOI：——

  日期：——
• STUART, A.;PATERSON, T.;ROTH, B.;AIG, E., J. MED. CHEM., 1983, 26, N 5, 667-673
  作者：STUART, A.、PATERSON, T.、ROTH, B.、AIG, E.

  DOI：——

  日期：——
• ROTH B.; RAUCKMAN B. S.; FERONE R.; BACCANARI D. P.; CHAMPNESS J. N.; HYD+, J. MED. CHEM., 30,(1987) N 2, 348-356
  作者：ROTH B.、 RAUCKMAN B. S.、 FERONE R.、 BACCANARI D. P.、 CHAMPNESS J. N.、 HYD+

  DOI：——

  日期：——