N1-(4'-cyanophenyl)-5-(2'',6''-dimethyl-4''-hydroxymethylphenoxy)-4-hydroxymethyl-2-nitroaniline | 1393736-05-4

• 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: N1-(4'-cyanophenyl)-5-(2'',6''-dimethyl-4''-hydroxymethylphenoxy)-4-hydroxymethyl-2-nitroaniline
• 英文别名: N-(4'-cyanophenyl)-5-(4"-hydroxymethyl-2",6"-dimethylphenoxy)-4-hydroxymethyl-2-nitroaniline；4-[4-(Hydroxymethyl)-5-[4-(hydroxymethyl)-2,6-dimethylphenoxy]-2-nitroanilino]benzonitrile
• CAS: 1393736-05-4
• 化学式: C₂₃H₂₁N₃O₅
• 分子量: 419.437
• InChiKey: WDBWKMRICJELMX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  131
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N1-(4'-cyanophenyl)-5-(2'',6''-dimethyl-4''-hydroxymethylphenoxy)-4-hydroxymethyl-2-nitroaniline 在 5% Pd/C 、 氢气 作用下， 以 乙醇 为溶剂， 以61%的产率得到N1-(4'-cyanophenyl)-5-(4''-hydroxymethyl-2'',6''-dimethylphenoxy)-4-hydroxymethyl-1,2-phenylenediamine
  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 锂硼氢 、 硫酸 、 potassium tert-butylate 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 N1-(4'-cyanophenyl)-5-(2'',6''-dimethyl-4''-hydroxymethylphenoxy)-4-hydroxymethyl-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

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。
• US9340492B2
  申请人：——

  公开号：US9340492B2

  公开（公告）日：2016-05-17