N-(4'-cyanophenyl)-5-(4"-cyano-2",6"-dimethylphenoxy)-4-hydroxymethyl-2-nitroaniline | 1538624-96-2

• 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: N-(4'-cyanophenyl)-5-(4"-cyano-2",6"-dimethylphenoxy)-4-hydroxymethyl-2-nitroaniline
• 英文别名: 4-[5-(4-Cyanoanilino)-2-(hydroxymethyl)-4-nitrophenoxy]-3,5-dimethylbenzonitrile；4-[5-(4-cyanoanilino)-2-(hydroxymethyl)-4-nitrophenoxy]-3,5-dimethylbenzonitrile
• CAS: 1538624-96-2
• 化学式: C₂₃H₁₈N₄O₄
• 分子量: 414.42
• InChiKey: RXIGUJGATHKTRY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  135
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-(4'-cyanophenyl)-5-(4"-cyano-2",6"-dimethylphenoxy)-4-hydroxymethyl-2-nitroaniline 在 三聚氯氰 、 5%-palladium/activated carbon 、 氢气 作用下， 以 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、379.22 kPa 条件下， 反应 4.9h， 生成 4-[4-Amino-5-(4-cyanoanilino)-2-(methylaminomethyl)phenoxy]-3,5-dimethylbenzonitrile
  参考文献：
  名称：

  Physicochemical property-driven optimization of diarylaniline compounds as potent HIV-1 non-nucleoside reverse transcriptase inhibitors

  摘要：

  Using physicochemical property-driven optimization, twelve new diarylaniline compounds (DAANs) (7a-h, 11a-b and 12a-b) were designed and synthesized. Among them, compounds 12a-b not only showed high potency (EC50 0.96-4.92 nM) against both wild-type and drug-resistant viral strains with the lowest fold change (FC 0.91 and 5.13), but also displayed acceptable drug-like properties based on aqueous solubility and lipophilicity (LE>0.3, LLE>5, LELP<10). The correlations between potency and physicochemical properties of these DAAN analogues are also described. Compounds 12a-b merit further development as potent clinical trial candidates against AIDS.

  DOI：

  10.1016/j.bmcl.2014.07.011
• 作为产物：
  描述：

  5-chloro-N1-(4-cyanophenyl)-4-methoxycarbonyl-2-nitroaniline 在 锂硼氢 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 生成 N-(4'-cyanophenyl)-5-(4"-cyano-2",6"-dimethylphenoxy)-4-hydroxymethyl-2-nitroaniline
  参考文献：
  名称：

  Physicochemical property-driven optimization of diarylaniline compounds as potent HIV-1 non-nucleoside reverse transcriptase inhibitors

  摘要：

  Using physicochemical property-driven optimization, twelve new diarylaniline compounds (DAANs) (7a-h, 11a-b and 12a-b) were designed and synthesized. Among them, compounds 12a-b not only showed high potency (EC50 0.96-4.92 nM) against both wild-type and drug-resistant viral strains with the lowest fold change (FC 0.91 and 5.13), but also displayed acceptable drug-like properties based on aqueous solubility and lipophilicity (LE>0.3, LLE>5, LELP<10). The correlations between potency and physicochemical properties of these DAAN analogues are also described. Compounds 12a-b merit further development as potent clinical trial candidates against AIDS.

  DOI：

  10.1016/j.bmcl.2014.07.011

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
• Physicochemical property-driven optimization of diarylaniline compounds as potent HIV-1 non-nucleoside reverse transcriptase inhibitors
  作者：Na Liu、Bingjie Qin、Lian-Qi Sun、Fei Yu、Lu Lu、Shibo Jiang、Kuo-Hsiung Lee、Lan Xie

  DOI：10.1016/j.bmcl.2014.07.011

  日期：2014.8

  Using physicochemical property-driven optimization, twelve new diarylaniline compounds (DAANs) (7a-h, 11a-b and 12a-b) were designed and synthesized. Among them, compounds 12a-b not only showed high potency (EC50 0.96-4.92 nM) against both wild-type and drug-resistant viral strains with the lowest fold change (FC 0.91 and 5.13), but also displayed acceptable drug-like properties based on aqueous solubility and lipophilicity (LE>0.3, LLE>5, LELP<10). The correlations between potency and physicochemical properties of these DAAN analogues are also described. Compounds 12a-b merit further development as potent clinical trial candidates against AIDS.