2,4-diamino-5-(4-chlorophenyl)-6-methylpyrimidine | 3275-44-3

• 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-(4-chlorophenyl)-6-methylpyrimidine
• 英文别名: 5-(4-chlorophenyl)-6-methylpyrimidine-2,4-diamine；5-(p-chlorophenyl)-2,4-diamino-6-methylpyrimidine；5-(4-chloro-phenyl)-6-methyl-pyrimidine-2,4-diamine；5-(4-chloro-phenyl)-6-methyl-pyrimidine-2,4-diyldiamine；5-(4-Chlor-phenyl)-6-methyl-pyrimidin-2,4-diyldiamin；2,4-diamino-5-(p-chlorophenyl)-6-methylpyrimidine
• CAS: 3275-44-3
• 化学式: C₁₁H₁₁ClN₄
• 分子量: 234.688
• InChiKey: SNBBQZGVKQEBQT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 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

反应信息

• 作为反应物：
  描述：

  2,4-diamino-5-(4-chlorophenyl)-6-methylpyrimidine 在 盐酸 、 sodium azide 、 硫酸 、 硝酸 、 tin(ll) chloride 、 sodium nitrite 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 2,4-diamino-5-(3-azido-4-chlorophenyl)-6-methylpyrimidine ethanesulphonic acid salt
  参考文献：
  名称：

  生物活性化合物的结构研究。第5部分。带有亲脂性叠氮基的2,4-二氨基嘧啶二氢叶酸还原酶抑制剂的合成和性质

  摘要：

  已经制备了一系列的2，4-二氨基-5-（叠氮芳基）-6-烷基嘧啶。叠氮化物（36）（MZP）可以通过硫醇试剂还原为相应的胺（28），但是当一系列叠氮基苯基衍生物与水合肼一起加热时，会发生还原脱叠作用。在三氟乙酸-三氟甲磺酸混合物中于0°C降解叠氮化物（36）提供了一种将庞大的三氟甲基磺酰氧基取代基引入到5-芳基取代基的受阻邻位中的方法。由叠氮化物（36）和平面类似物2,4-二氨基-6-叠氮喹啉（70）的热解和光解形成的产物）衍生自三重态腈反应性中间体。

  DOI：

  10.1039/p19870002217
• 作为产物：
  描述：

  对氯苯乙腈 在 disodium hydrogenphosphate 、 sodium amalgam 、 copper(l) iodide 、 sodium ethanolate 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 为溶剂， 反应 28.0h， 生成 2,4-diamino-5-(4-chlorophenyl)-6-methylpyrimidine
  参考文献：
  名称：

  从甲基苯基砜合成重要的药学杂芳烃

  摘要：

  3-甲硫基-1-苯基-4-苯基磺酰基-2-丁烯-1-酮(5a)或(E)-1-对氯苯基-1-氰基-2-甲硫基制备了一些5-取代的吡唑和乙胺嘧啶-3-苯磺酰基丙烯（6b），它可以很容易地从甲基苯砜合成。

  DOI：

  10.1246/bcsj.57.2954

文献信息

• 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。
• 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.
• Pyrimethamine Derivatives: Insight into Binding Mechanism and Improved Enhancement of Mutant β-<i>N</i>-acetylhexosaminidase Activity
  作者：Michael B. Tropak、Jianmin Zhang、Sayuri Yonekawa、Brigitte A. Rigat、Virender S. Aulakh、Matthew R. Smith、Hee-Jong Hwang、Marco A. Ciufolini、Don J. Mahuran

  DOI：10.1021/jm5017895

  日期：2015.6.11

  In order to identify structural features of pyrimethamine (5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine) that contribute to its inhibitory activity (IC50 value) and chaperoning efficacy toward beta-N-acetylhexosaminidase, derivatives of the compound were synthesized that differ at the positions bearing the amino, ethyl, and chloro groups. Whereas the amino groups proved to be critical to its inhibitory activity, a variety of substitutions at the chloro position only increased its IC50 by 2-3-fold. Replacing the ethyl group at the 6-position with butyl or methyl groups increased IC50 more than 10-fold. Surprisingly, despite its higher IC50, a derivative lacking the chlorine atom in the para-position was found to enhance enzyme activity in live patient cells a further 25% at concentrations >100 mu M, while showing less toxicity. These findings demonstrate the importance of the phenyl group in modulating the chaperoning efficacy and toxicity profile of the derivatives.
• YOKOYAMA, MASATAKA;TSUJI, KOUICHI;IMAMOTO, TSUNEO, BULL. CHEM. SOC. JAP., 1984, 57, N 10, 2954-2956
  作者：YOKOYAMA, MASATAKA、TSUJI, KOUICHI、IMAMOTO, TSUNEO

  DOI：——

  日期：——
• BLISS, EDWARD A.;GRIFFIN, ROGER J.;STEVENS, MALCOLM F. G., J. CHEM. SOC. PERKIN TRANS., 1,(1987) N 10, 2217-2228
  作者：BLISS, EDWARD A.、GRIFFIN, ROGER J.、STEVENS, MALCOLM F. G.

  DOI：——

  日期：——