2-(4-cyanophenylamino)-4-(4-cyanophenylhydroxymethyl)pyrimidine | 1617527-86-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(4-cyanophenylamino)-4-(4-cyanophenylhydroxymethyl)pyrimidine
• 英文别名: 4-((4-((4-cyanophenyl)(hydroxy)methyl)pyrimidin-2-yl)amino)benzonitrile；4-[[2-(4-Cyanoanilino)pyrimidin-4-yl]-hydroxy-methyl]benzonitrile；4-[[2-(4-cyanoanilino)pyrimidin-4-yl]-hydroxymethyl]benzonitrile
• CAS: 1617527-86-2
• 化学式: C₁₉H₁₃N₅O
• 分子量: 327.345
• InChiKey: DDPBDSWJOJVWKW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-N[2(4-氯吡啶基)]-氨基苯腈 在 钾硼氢 、 sodium hydride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.33h， 生成 2-(4-cyanophenylamino)-4-(4-cyanophenylhydroxymethyl)pyrimidine
  参考文献：
  名称：

  Design and synthesis of a new series of modified CH-diarylpyrimidines as drug-resistant HIV non-nucleoside reverse transcriptase inhibitors

  摘要：

  This article reports the design, synthesis and antiviral evaluation of a new series of non-nucleoside reverse transcriptase inhibitors (NNRTIs). The basic skeleton of these target 18 molecules is diarylpyrimidine featuring a substituted amino group between the pyrimidine scaffold and the aryl wing. All of the new compounds have been characterized by spectra analysis. The entire target molecules were evaluated for their in vitro anti-HIV activity with controlling group of FDA approved drugs. Most of them showed good to potent activities against wild-type (WT) HIV-1 with IC50 values in the range of 0.0175-69.21 mu M. 2-(4-Cyanophenylamino)-4-(2-cyanovinylphenylhydrazonomethyl)pyrimidine (1d) displayed potent anti-HIV-1 activity against WT HIV-1 with a selectivity index (SI) of 106367 and an IC50 value of 1.75 nM, which was 47 fold lower than that of AZT. Compound Id also showed a broad-spectrum inhibitory activity, with an IC50 value of 5.33 mu M and 5.05 mu M against both HIV-1 double-mutated (K103N/Y181C) strain and HIV-2 strain, respectively. The preliminary structure activity relationship (SAR) was also investigated. The binding modes with HIV-1 RT for both the wild type and mutant type have also been discussed. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.05.059

文献信息

• Novel (2,6-difluorophenyl)(2-(phenylamino)pyrimidin-4-yl)methanones with restricted conformation as potent non-nucleoside reverse transcriptase inhibitors against HIV-1
  作者：Petr Šimon、Ondřej Baszczyňski、David Šaman、George Stepan、Eric Hu、Eric B. Lansdon、Petr Jansa、Zlatko Janeba

  DOI：10.1016/j.ejmech.2016.06.026

  日期：2016.10

  carbonyl linker between the central pyrimidine core and phenyl type B-arm, a series of (2,6-difluorophenyl)(2-(phenylamino)pyrimidin-4-yl)methanones was designed, prepared and tested for their anti-HIV-1 activity. The carbonyl linker bearing B phenyl arm was successfully attached at both C-2 and C-4 positions of the central pyrimidine ring using a new synthetic approach. Further modifications of target

  为了阐明在中央嘧啶核和苯基B-臂之间含有羰基连接基的二芳基嘧啶家族（DAPYs）中的结构-几何-活性关系，需要一系列（2,6-二氟苯基）（2-（苯基氨基）嘧啶-4-设计，制备和测试yl）甲烷的抗HIV-1活性。使用新的合成方法，带有B苯基臂的羰基连接基已成功连接到中央嘧啶环的C-2和C-4位置。目标化合物的进一步修饰存在于嘧啶环的C-5位。体外在一系列22种化合物上进行的抗HIV-1活性研究证实了苯基B臂与通过羰基桥连接的嘧啶核之间的构象刚性以及苯基B的邻位上存在氟取代基的构象刚性至关重要部分。该系列中最有效的衍生物（化合物17）在两个由B芳族臂和嘧啶环制成的平面内具有几乎垂直的角度，显示出低纳摩尔抗HIV-1活性（EC 50  = 4 nM），无明显毒性（CC 50  > 57.1μM）。