5-(4-bromophenyl)-6-ethylpyrimidine-2,4-diamine | 7331-26-2

• 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: 5-(4-bromophenyl)-6-ethylpyrimidine-2,4-diamine
• 英文别名: 6-ethyl-5-(4-bromo-phenyl)-pyrimidine-2,4-diyldiamine；6-Aethyl-5-(4-brom-phenyl)-pyrimidin-2,4-diyldiamin
• CAS: 7331-26-2
• 化学式: C₁₂H₁₃BrN₄
• 分子量: 293.166
• InChiKey: QBWDUOPHQODKEA-UHFFFAOYSA-N

物化性质

• 熔点：
  213-216 °C
• 沸点：
  510.0±60.0 °C(Predicted)
• 密度：
  1.505±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 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：

  5-(4-bromophenyl)-6-ethylpyrimidine-2,4-diamine 在 吡啶 、 4-二甲氨基吡啶 、 copper(l) iodide 、 四(三苯基膦)钯 、 caesium carbonate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 3.17h， 生成 di-tert-butyl (6-ethyl-5-(4′-vinyl-[1,1′-biphenyl]-4-yl)pyrimidine-2,4-diyl)bis(tert-butoxycarbonylcarbamate)
  参考文献：
  名称：

  Pyrimethamine conjugated histone deacetylase inhibitors: Design, synthesis and evidence for triple negative breast cancer selective cytotoxicity

  摘要：

  Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor which has been recognized as a promising cancer therapeutic target. Small molecule pyrimethamine (PYM) is a known direct inhibitor of activated STAT3 and it is currently under clinical trial. Also, histone deacetylase (HDAC) inhibition has been shown to indirectly attenuate STAT3 signaling through inhibition of STAT3 activation. Herein we described the design and biological profiling of two classes of PYM-conjugated HDAC inhibitors (HDACi). We observed that the class I PYM-HDACi compounds 12a-c potently inhibited HDACs 1 and 6 in cell free assays while a lead class II PYM-HDACi compound 23 showed a strong HDAC 6 selective inhibition. In a cell-based assay, 12a-c are preferentially cytotoxic to MDA-MB-231, a TNBC cell line that is highly STAT3-dependent, while 23 showed no such selective toxicity. Subsequent target validation studies revealed that a representative class I PYM-HDACi compound 12c elicited a signature of HDAC and STAT3 pathway inhibition intracellularly. Collectively, these data suggest that PYM-HDACi compounds are promising leads to develop targeted therapy for TNBC.

  DOI：

  10.1016/j.bmc.2020.115345
• 作为产物：
  描述：

  对溴苯乙腈 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二甲基亚砜 为溶剂， 反应 0.25h， 生成 5-(4-bromophenyl)-6-ethylpyrimidine-2,4-diamine
  参考文献：
  名称：

  Development of 2,4-Diaminopyrimidines as Antimalarials Based on Inhibition of the S108N and C59R+S108N Mutants of Dihydrofolate Reductase from Pyrimethamine-Resistant Plasmodium falciparum

  摘要：

  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.

  DOI：

  10.1021/jm010131q

文献信息

• 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
• α-Aryl-β-alkyloxyacrylonitriles
  作者：Peter B. Russell、Norman Whittaker

  DOI：10.1021/ja01125a049

  日期：1952.3