5-(4''-formyl-2'',6''-dimethylphenoxy)-N1-(4'-cyanophenyl)-4-methoxycarbonyl-2-nitroaniline | 1372129-85-5

• 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: 5-(4''-formyl-2'',6''-dimethylphenoxy)-N1-(4'-cyanophenyl)-4-methoxycarbonyl-2-nitroaniline
• 英文别名: N1-(4'-cyanophenyl)-5-(2'',6''-dimethyl-4''-formylphenoxy)-4-methoxycarbonyl-2-nitroaniline
• CAS: 1372129-85-5
• 化学式: C₂₄H₁₉N₃O₆
• 分子量: 445.431
• InChiKey: DHDVFNOWDKGZFS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.22
• 重原子数：
  33.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  131.56
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  5-(4''-formyl-2'',6''-dimethylphenoxy)-N1-(4'-cyanophenyl)-4-methoxycarbonyl-2-nitroaniline 在 氯化亚砜 、 potassium tert-butylate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 11.0h， 生成 N1-(4'-cyanophenyl)-5-(4''-(2-cyanovinyl)-2'',6''-dimethylphenoxy)-4-methylcarbamoyl-2-nitroaniline
  参考文献：
  名称：

  Design, Synthesis, and Preclinical Evaluations of Novel 4-Substituted 1,5-Diarylanilines as Potent HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) Drug Candidates

  摘要：

  Twenty-one new 4-substituted diarylaniline compounds (DAANs) (series 13, 14, and 15) were designed, synthesized, and evaluated against wildtype and drug resistant HIV-1 viral strains. As a result, approximately a dozen new DAANs showed high potency with low nano- to subnanomolar EC50 values ranging from 0.2 to 10 nM. The three most promising compounds 14e, 14h, and 15h exhibited high potency against wild-type and drug-resistant viral strains with EC50 values at the subnanomolar level (0.29-0.87 nM) and were comparable to or more potent than the new NNRTI drug riplivirine (2) in the same assays. Drug like physicochemical property assessments revealed that the most active DAANs (EC50 < 10 nM) have better aqueous solubility (>1-90 mu g/mL at pH 7.4 and pH 2) and metabolic stability in vitro than 2, as well as desirable log P values (<5) and polar surface areas (PSA) (<140 A(2)). These promising results warrant further development of this novel compound class as potential potent anti-AIDS clinical trial candidates.

  DOI：

  10.1021/jm3007678
• 作为产物：
  描述：

  2,4-二氯-5-硝基苯甲酸 在 硫酸 、 potassium carbonate 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.25h， 生成 5-(4''-formyl-2'',6''-dimethylphenoxy)-N1-(4'-cyanophenyl)-4-methoxycarbonyl-2-nitroaniline
  参考文献：
  名称：

  Optimization of 2,4-diarylanilines as non-nucleoside HIV-1 reverse transcriptase inhibitors

  摘要：

  The current optimization of 2,4-diarylaniline analogs (DAANs) on the central phenyl ring provided a series of new active DAAN derivatives 9a-9e, indicating an accessible modification approach that could improve anti-HIV potency against wild-type and resistant strains, aqueous solubility, and metabolic stability. A new compound 9e not only exhibited extremely high potency against wild-type virus (EC50 0.53 nM) and several resistant viral strains (EC50 0.36-3.9 nM), but also showed desirable aqueous solubility and metabolic stability, which were comparable or better than those of the anti-HIV-1 drug TMC278 (2). Thus, new compound 9e might be a potential drug candidate for further development of novel next-generation NNRTIs. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.055

文献信息

• META-DIARYLANILINE OR META-DIARYLPYRIDINAMINE COMPOUND, PREPARATION METHOD AND MEDICAL USES THEREOF
  申请人：INSTITUTE OF PHARMACOLOGY AND TOXICOLOGY ACADEMY OF MILITARY MEDICAL SCIENCES P.L.A. CHINA

  公开号：US20150218088A1

  公开（公告）日：2015-08-06

  Meta-diarylaniline or meta-diarylpyridinamine compounds, methods for preparing the same and uses thereof in manufacture of a medicament. The compounds according to the present application have strong inhibitory activity (at nM level) against wild-type and various drug-resistant HIV viral strains, exhibit good druggability, and can be easily synthesized.

  元-二芳基苯胺或元-二芳基吡啶胺化合物，其制备方法以及在制造药物方面的用途。根据本申请的化合物在nM水平上对野生型和各种耐药性HIV病毒株具有强烈的抑制活性，表现出良好的药物可达性，并且可以容易地合成。