2,4-diamino-5-(3-methoxy-4-allyloxy-benzyl)-pyrimidine | 121936-22-9

• 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-methoxy-4-allyloxy-benzyl)-pyrimidine
• 英文别名: 2,4-Pyrimidinediamine, 5-((3-methoxy-4-(2-propenyloxy)phenyl)methyl)-；5-[(3-methoxy-4-prop-2-enoxyphenyl)methyl]pyrimidine-2,4-diamine
• CAS: 121936-22-9
• 化学式: C₁₅H₁₈N₄O₂
• 分子量: 286.334
• InChiKey: HIBNJZOVXZFUJA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  96.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,4-diamino-5-(3-methoxy-4-allyloxy-benzyl)-pyrimidine 以 various solvent(s) 为溶剂， 反应 4.5h， 以43%的产率得到2,4-diamino-5-(3-allyl-4-hydroxy-5-methoxybenzyl)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：

  2,4-diamino-5-(3-methoxy-4-hydroxybenzyl)pyrimidine 、 3-溴丙烯 在 potassium tert-butylate 作用下， 以 二甲基亚砜 、 叔丁醇 为溶剂， 以54%的产率得到2,4-diamino-5-(3-methoxy-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

文献信息

• Benzyldiaminopyrimidin-Derivate und deren Verwendung als Arzneimittel
  申请人：EGIS GYOGYSZERGYAR

  公开号：EP0301428A2

  公开（公告）日：1989-02-01

  Gegenstand der Erfindung ist die Verwendung von 5­-(substituierten Benzyl) 2,4-Di-(amino)-pyrimidinderiva­ten der allgemeinen Formel worin R₁ und R₂ , die gleich oder verschieden sein können, für Wasserstoffatome, Hydroxygruppen, Alkoxyreste mit 1 bis 6 Kohlenstoffatom(en), Al­koxyalkoxyreste mit 1 bis 6 Koh­lenstoffatom(en) in jedem Alkoxy­teil, Alkenyloxyreste mit 2 bis 6 Kohlenstoffatomen beziehungsweise Phenylalkoxyreste mit 1 bis 3 Kohlenstoffatom(en) im Alkoxyteil stehen oder R₁ und R₂ zusammen einen Alkylendioxyrest mit 1 oder 2 Kohlenstoffatom(en) darstellen, mit der weiteren Maßgabe, daß mindestens 1 von R₁ und R₂ von Wasser­stoff ver­schieden ist, sowie ihre Säureadditionssalze zur Herstellung von antipyretisch, entzündungshemmend einschließlich an­tirheumatisch, anti-anginös und/oder antioxydierend wirkenden Arzneimitteln. Gegenstand der Erfindung sind auch die neuen Verbin­dungen unter diesen.

  本发明的主题是使用通式为 5-(取代的苄基)2,4-二(氨基)-嘧啶衍生物 其中 R₁和 R₂，可以相同或不同，代表氢原子、羟基、具有 1 至 6 个碳原子的烷氧基、每个烷氧基中具有 1 至 6 个碳原子的烷氧基、具有 2 至 6 个碳原子的烯氧基或烷氧基中具有 1 至 3 个碳原子的苯基烷氧基，或 R₁ 和 R₂ 共同代表具有 1 或 2 个碳原子的烷二氧基、 进一步的条件是 R₁ 和 R₂ 中至少有一个不是氢、 以及它们的酸加成盐，用于制备具有解热、消炎（包括抗风湿）、抗心绞痛和/或抗氧化活性的药物。 其中的新化合物也是本发明的主题。
• 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：——
• US4883798A
  申请人：——

  公开号：US4883798A

  公开（公告）日：1989-11-28
• 2,4-Diamino-5-benzylpyrimidines as antibacterial agents. 13. Some alkenyl derivatives with high in vitro activity against anaerobic organisms
  作者：Barbara Roth、Mary Y. Tidwell、Robert Ferone、David P. Baccanari、Carl W. Sigel、Diane DeAngelis、Lynn P. Elwell

  DOI：10.1021/jm00128a043

  日期：1989.8

  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.