2,4-Diamino-5-(3,5-diaethyl-4-hydroxybenzyl)-pyrimidin | 36821-97-3

• 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-(3,5-diaethyl-4-hydroxybenzyl)-pyrimidin
• 英文别名: 4-(2,4-diamino-pyrimidin-5-ylmethyl)-2,6-diethyl-phenol；2,4-diamino-5-(3,5-diethyl-4-hydroxybenzyl)pyrimidine；4-[(2,4-diaminopyrimidin-5-yl)methyl]-2,6-diethylphenol
• CAS: 36821-97-3
• 化学式: C₁₅H₂₀N₄O
• 分子量: 272.35
• InChiKey: VUYZAOCZFHLOER-UHFFFAOYSA-N

物化性质

• 沸点：
  525.1±60.0 °C(Predicted)
• 密度：
  1.216±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 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：

  3-苯氧基溴丙烷 、 2,4-Diamino-5-(3,5-diaethyl-4-hydroxybenzyl)-pyrimidin 在 氢氧化钾 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以62%的产率得到2,4-diamino-5-[3,5-diethyl-4-(3-phenoxypropoxy)benzyl]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
• 作为产物：
  描述：

  5-(溴甲基)-2,4-嘧啶二胺 、 2,6-二乙基苯酚 以2,4-diamino-5-(3,5-diethyl-4-hydroxybenzyl)pyrimidine was obtained in a yield of approximately 65%的产率得到2,4-Diamino-5-(3,5-diaethyl-4-hydroxybenzyl)-pyrimidin
  参考文献：
  名称：

  Organic synthetic methods benzylpyrimidine derivatives

  摘要：

  一种制备2,4-二氨基-5-苄基嘧啶的方法，包括将2,4-二氨基-5-取代甲基嘧啶（例如2,4-二氨基-5-羟甲基嘧啶）与适当取代的苯酚反应。

  公开号：

  US04116958A1

文献信息

• 2,4-Diamino-5-benzylpyrimidines, especially for the treatment of microbial infections, pharmaceutical compositions containing these compounds and processes for preparing these compounds
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0006987A1

  公开（公告）日：1980-01-23

  Pharmaceutical compositions containing 2,4-diamino-5-(3. 5-dialkyl-4-hydroxybenzyl) pyrimidines wherein the alkyl groups contain from 2 to 4 carbon atoms are useful in the treatment of bacterial infections. The first medical use of such compounds, novel chemical compounds wherein the alkyl groups are propyl or butyl, except the di-i-propyl compound, a process for preparing the novel compounds and chemical intermediates used in their preparation are also disclosed.

  含有 2,4-二氨基-5-(3. 5-二烷基-4-羟基苄基)嘧啶（其中烷基含有 2 至 4 个碳原子）的药物组合物可用于治疗细菌感染。此外，还公开了此类化合物的第一种医学用途、烷基为丙基或丁基的新型化合物（二丙基化合物除外）、制备新型化合物的工艺以及用于制备这些化合物的化学中间体。
• Antibacterial benzylpyrimidines
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0054756A2

  公开（公告）日：1982-06-30

  Compounds of the formula (IV): or acid addition salts thereof, wherein one of the groups R5 is a group O(CH2)nYR7 wherein Y is an oxygen or sulphur atom or a methylene, OCH2 or SCH2 group, n is an integer from 1 to 5 and R7 is an optionally substituted phenyl group; the other group R5 and R6 being the same or different, each being hydrogen, halogen, C2-4alkenyl, C2-4alkenyloxy, nitro, cyano, hydroxy, benzyloxy, C1-4alkyl or C1-4alkoxy, the alkyl or alkoxy group being substituted by halogen, hydroxy, or C1-2alkoxy; amino optionally substituted by one or two C1-4 alkyl or C1-4acyl groups or the nitrogen atom forming part of a five or six membered heterocyclic ring, a group -OSO2R8 or S(O)rR8 wherein R8 is C1-3alkyl and r is 0,1 or 2 a group -COR9 wherein R9 is methyl, ethyl, methoxy, ethoxy, amino, methylamino, ethylamino, dimethylamino or diethylamino, are useful for the treatment of bacterial infections. A process for preparing these compounds and novel chemical intermediates used in their preparation are disclosed as is the first medical use of the compounds of the formula (IV) and pharmaceutical compositions containing them.

  式 (IV) 的化合物： 或其酸加成盐，其中一个基团 R5 是基团 O(CH2)nYR7，其中 Y 是氧原子或硫原子或亚甲基、OCH2 或 SCH2 基团，n 是 1 至 5 的整数，R7 是任选取代的苯基；另一个基团 R5 和 R6 相同或不同，各自为氢、卤素、C2-4 烷基、C2-4 烷氧基、硝基、氰基、羟基、苄氧基、C1-4 烷基或 C1-4 烷氧基，烷基或烷氧基被卤素、羟基或 C1-2 烷氧基取代；被一个或两个 C1-4 烷基或 C1-4acyl 基团或构成五或六位杂环的氮原子任选取代的氨基、基团 -OSO2R8 或 S(O)rR8 （其中 R8 为 C1-3 烷基，r 为 0、1 或 2）、基团 -COR9 （其中 R9 为甲基、乙基、甲氧基、乙氧基、氨基、甲氨基、乙氨基、二甲氨基或二乙氨基），可用于治疗细菌感染。本发明公开了制备这些化合物的工艺以及用于制备这些化合物的新型化学中间体，并首次公开了式 (IV) 化合物的医学用途以及含有这些化合物的药物组合物。
• 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：——
• US4116958A
  申请人：——

  公开号：US4116958A

  公开（公告）日：1978-09-26
• 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
  作者：Barbara Roth、Barbara S. Rauckman、Robert Ferone、David P. Baccanari、John N. Champness、Richard M. Hyde

  DOI：10.1021/jm00385a017

  日期：1987.2

  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.