6-甲基-5-苯基-2,4-嘧啶二胺 | 18588-50-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 6-甲基-5-苯基-2,4-嘧啶二胺
• 英文名称: 6-methyl-5-phenyl-pyrimidine-2,4-diamine
• 英文别名: 6-methyl-5-phenyl-pyrimidine-2,4-diyldiamine；6-Methyl-5-phenyl-pyrimidin-2,4-diyldiamin；2,4-Diamino-5-phenyl-6-methyl-pyrimidin；2,4-Diamino-5-phenyl-6-methylpyrimidin；2,4-Diamino-5-phenyl-6-methylpyrimidine；6-methyl-5-phenylpyrimidine-2,4-diamine
• CAS: 18588-50-6
• 化学式: C₁₁H₁₂N₄
• 分子量: 200.243
• InChiKey: RBOOBZAJMOATAV-UHFFFAOYSA-N

物化性质

• 熔点：
  249-250 °C
• 沸点：
  327.97°C (rough estimate)
• 密度：
  1.2007 (rough estimate)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  77.8
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  6-甲基-5-苯基-2,4-嘧啶二胺 在 air 、 hematoporphyrin 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以83%的产率得到4-amino-6-methyl-1,3,5-triazin-2-yl phenyl ketone
  参考文献：
  名称：

  5-芳基-2,4-二氨基嘧啶的光氧合反应生成4-氨基-1,3,5-三嗪-2-基酮，并在存在硼氢化钠的情况下生成5,6-二氢-4-（3 H） -嘧啶酮

  摘要：

  5-芳基-2,4-二氨基嘧啶1在质子溶剂中的光敏氧化导致高产率地形成新的4-氨基-1,3-5-三嗪-2-基酮2。通过光谱方法，特别是通过13 C-NMR和UV数据阐明了2的结构。在还原条件下，例如在过量的NaBH 4存在下，对2,4-二氨基-5-（对氯苯基）-6-乙基嘧啶1a进行光氧化，得到2-氨基-5-（对氯苯基）-t -6-乙基-5,6-二氢-r -5-羟基-4（3H）-嘧啶酮（4a），其结构是通过X射线分析确定的。在针对两种类型反应的拟议机制中，偶极离子5被认为是共同的中间体。对于由2，4-二氨基嘧啶新有效地合成1,3,5-三嗪，一个5-芳基取代基似乎是必不可少的。

  DOI：

  10.1002/hlca.19880710405
• 作为产物：
  描述：

  α-苯乙酰乙腈 在 乙醇 、 sodium ethanolate 、 对甲苯磺酸 作用下， 生成 6-甲基-5-苯基-2,4-嘧啶二胺
  参考文献：
  名称：

  707.由某些β-酮腈制备烯醇醚

  摘要：

  DOI：

  10.1039/jr9530003518

文献信息

• Structure-based design, synthesis and preliminary evaluation of selective inhibitors of dihydrofolate reductase from Mycobacterium tuberculosis
  作者：Mervat H.R.I. El-Hamamsy、Anthony W. Smith、Andrew S. Thompson、Michael D. Threadgill

  DOI：10.1016/j.bmc.2007.04.011

  日期：2007.7

  structure of M. tuberculosis DHFR revealed a glycerol tightly bound close to the binding site for the substrate dihydrofolate; this glycerol-binding motif is absent from the human enzyme. A series of pyrimidine-2,4-diamines was designed with a two-carbon tether between a glycerol-mimicking triol and the 6-position of the heterocycle; these compounds also carried aryl substituents at the 5-position. These

  由于艾滋病的传播以及病原性微生物结核分枝杆菌对目前可用药物的耐药性的发展，结核病的威胁日益增加。二氢叶酸还原酶（DHFR）是叶酸循环中的重要酶。抑制DHFR会抑制生长并导致细胞死亡。结核分枝杆菌DHFR的晶体结构显示甘油紧密结合在底物二氢叶酸的结合位点附近。人类酶中没有这种甘油结合基序。设计了一系列嘧啶-2,4-二胺，在模仿甘油的三醇和杂环的6-位之间使用双碳链。这些化合物还在5-位带有芳基取代基。这些非对映异构体 缺少两个羟基的类似物和缺少两个碳间隔连接基的类似物是通过用（4S，5R）-4-苄氧基甲基-2,2-二甲基-1,3-二氧戊环-4-乙基酰化苯乙腈衍生的阴离子而合成的丙酸酯，（4S，5S）-4-苄氧基甲基-2,2-二甲基-1,3-二氧戊环-4-丙酸酯，四氢氧杂-2-酮和2,3-O-异亚丙基-d-赤藓内酯得到相应的α-酰基苯基乙腈。形成甲基烯醇醚，与胍缩合并脱保护得到嘧啶-2，4-二
• COMPOUNDS FOR THE TREATMENT OF LYSOSOMAL STORAGE DISEASES
  申请人：MAHURAN Don

  公开号：US20110195985A1

  公开（公告）日：2011-08-11

  A method of treating a lysosomal storage disease comprises administering a pyrimethamine derivative to a subject in need thereof.

  一种治疗溶酶体贮积病的方法，包括向需要治疗的受试者给予嘧啶甲酰胺衍生物。
• Syntheses of 2,4-Diaminopyrimidines and 1-Aminoisoquinolines in the Reactions of Alkyl and Benzyl Ketones with Cyanamide and N,N-dimethylcyanamide
  作者：Wojciech Zielinski、Monika Mazik

  DOI：10.3987/com-93-6583

  日期：——

  The reaction of alkyl and benzyl ketones with cyanamide and N,N-dimethylcyanamide in the presence of POCl3 was examined. At the first stage, chloroformamidine derivatives were formed. In the presence of TiCl4, they underwent further reactions to the derivatives of 1-aminoisoquinoline and 2,4-diaminopyrimidine. The effect of a constitution of substrates on adequate ratios of heterocyclic compounds is discussed.
• 2,4-Diaminopyrimidines as Antimalarials. III. 5-Aryl Derivatives
  作者：Peter B. Russell、George H. Hitchings

  DOI：10.1021/ja01152a060

  日期：1951.8
• Development of 2,4-Diaminopyrimidines as Antimalarials Based on Inhibition of the S108N and C59R+S108N Mutants of Dihydrofolate Reductase from Pyrimethamine-Resistant <i>Plasmodium </i><i>f</i><i>alciparum</i>
  作者：Bongkoch Tarnchompoo、Chawanee Sirichaiwat、Worrapong Phupong、Chakapong Intaraudom、Worachart Sirawaraporn、Sumalee Kamchonwongpaisan、Jarunee Vanichtanankul、Yodhathai Thebtaranonth、Yongyuth Yuthavong

  DOI：10.1021/jm010131q

  日期：2002.3.1

  The reduced binding of pyrimethamine to Ser 108Asn (S108N) mutants of parasite dihydrofolate reductase (DHFR), which forms the basis of resistance of Plasmodium falcipartum to pyrimethamine, is largely due to steric constraint imposed by the bulky side chain of N108 on Cl of the 5-p-Cl-phenyl group. This and other S108 mutants with bulky side chains all showed reduced binding to pyrimethamine and cycloguanil. Less effect on binding to some bulky mutants was observed for trimethoprim, with greater flexibility for the 5-substituent. S108N DHFR also binds poorly with other pyrimethamine derivatives with bulky groups in place of the p-Cl, and the binding was generally progressively poorer for the double (C59R+S108N) mutant. Removal of the p-Cl or replacement with m-Cl led to better binding with the mutant DHFRs. Pyrimethamine analogues with unbranched hydrophobic 6-substituents showed generally good binding with the mutant DHFRs. A number of compounds were identified with high affinities for both wild-type and mutant DHFRs, with very low to no affinity to human DHFR. Some of these compounds show good antimalarial activities against pyrimethamine-resistant P. falciparum containing the mutant DHFRs with low cytotoxicity to three mammalian cell lines.