2,4-diamino-5-(3-benzyloxy-4-methoxybenzyl)-pyrimidine | 78233-99-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2,4-diamino-5-(3-benzyloxy-4-methoxybenzyl)-pyrimidine
• 英文别名: 2,4-diamino-5-(3-benzyloxy-4-methoxybenzyl)pyrimidine；5-[[4-Methoxy-3-(phenylmethoxy)phenyl]methyl]-2,4-pyrimidinediamine；5-[(4-methoxy-3-phenylmethoxyphenyl)methyl]pyrimidine-2,4-diamine
• CAS: 78233-99-5
• 化学式: C₁₉H₂₀N₄O₂
• 分子量: 336.393
• InChiKey: XARRNBRDTOCYPU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  96.3
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  2,4-diamino-5-(3-benzyloxy-4-methoxybenzyl)-pyrimidine 在 钯 盐酸 作用下， 以 甲醇 为溶剂， 生成 2,4-diamino-5-(3'-hydroxy-4'-methoxybenzyl)pyrimidine hydrochloride
  参考文献：
  名称：

  Inhibitor of dihydrofolate reductase

  摘要：

  一组含有芳基-Z-烷氧基-5-苄基嘧啶的化合物已经通过2,4-二氨基-5-苄基嘧啶与芳基-Z-烷基卤代物或取代的环氧乙烷进行烷基化反应而制备出来。这些化合物是有效的二氢叶酸还原酶（DHFR）抑制剂，可用作抗菌、抗原虫和抗肿瘤剂。

  公开号：

  US04258045A1
• 作为产物：
  描述：

  (Z)-2-(anilinomethyl)-3-(4-methoxy-3-phenylmethoxyphenyl)prop-2-enenitrile 、 盐酸胍 生成 2,4-diamino-5-(3-benzyloxy-4-methoxybenzyl)-pyrimidine
  参考文献：
  名称：

  POE, M.;RUYLE, W. V.

  摘要：

  DOI：

文献信息

• Substituted 2,4-diamino-5-benzylpyrimidines, their preparation and their
  申请人：Saarstickstoff-Fatol GmbH Chem.-Pharm. Fabrik

  公开号：US04912112A1

  公开（公告）日：1990-03-27

  Novel substituted 2,4-diamino-5-benzyl pyrimidines are described. The novel substances have antimicrobial activity and are particularly suitable for inhibiting the growth of mycobacteria. Combined with inhibitors such as diaminodiphenylsulphones, ring-substituted 4-aminodiphenylsulphones or ring and/or nitrogen-substituted diaminodiphenylsulphones, they have a marked synergistic activity.

  描述了新型替代的2,4-二氨基-5-苄基嘧啶类化合物。这些新型物质具有抗微生物活性，特别适用于抑制分枝杆菌的生长。与抑制剂如二氨基二苯砜、环替代的4-氨基二苯砜或环和/或氮替代的二氨基二苯砜结合，它们具有明显的协同作用。
• Target Guided Synthesis of 5-Benzyl-2,4-diamonopyrimidines: Their Antimalarial Activities and Binding Affinities to Wild Type and Mutant Dihydrofolate Reductases from <i>Plasmodium falciparum</i>
  作者：Chawanee Sirichaiwat、Chakapong Intaraudom、Sumalee Kamchonwongpaisan、Jarunee Vanichtanankul、Yodhathai Thebtaranonth、Yongyuth Yuthavong

  DOI：10.1021/jm0303352

  日期：2004.1.1

  The resistance to pyrimethamine (PYR) of Plasmodium falciparum arising from mutation at position 108 of dihydrofolate reductase (pfDHFR) from serine to asparagine (S108N) is due to steric interaction between the bulky side chain of N108 and Cl atom of the 5-p-Cl aryl group of PYR, which consequently resulted in the reduction in binding affinity between the enzyme and inhibitor. Molecular modeling suggested that the flexible antifolate, such as trimethoprim (TMP) derivatives, could avoid this steric constraint and should be considered as new, potentially effective compounds. The hydrophobic interaction between the side chain of inhibitor and the active site of the enzyme around position 108 was enhanced by the introduction of a longer and more hydrophobic side chain on TMP's 5-benzyl moiety. The prepared compounds, especially those bearing aromatic substituents, exhibited better binding affinities to both wild type and mutant enzymes than the parent compound. Binding affinities of these compounds correlated well with their antimalarial. activities against both wild type and resistant parasites. Molecular modeling of the binding of such compounds with pfDHFR also supported the experimental data and clearly showed that aromatic substituents play an important role in enhancing binding affinity. In addition, some compounds with 6-alkyl substituents showed relatively less decrease in binding constants with the mutant enzymes and relatively good antimalarial. activities against the parasites bearing the mutant enzymes.
• Substituierte 2,4-Diamino-5-benzylpyrimidine, deren Herstellung und deren Verwendung als Arzneimittel mit antimikrobieller Wirksamkeit
  申请人：Fatol Arzneimittel GmbH

  公开号：EP0231888B1

  公开（公告）日：1992-12-30
• US4258045A
  申请人：——

  公开号：US4258045A

  公开（公告）日：1981-03-24
• US4912112A
  申请人：——

  公开号：US4912112A

  公开（公告）日：1990-03-27