5-(4''-cyanoethyl-2'',6''-dimethylphenoxy)-N1-(4'-cyanophenyl)-4-(N-methyl-carbamoyl)-1,2-phenylenediamine | 1393736-21-4

• 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: 5-(4''-cyanoethyl-2'',6''-dimethylphenoxy)-N1-(4'-cyanophenyl)-4-(N-methyl-carbamoyl)-1,2-phenylenediamine
• 英文别名: 5-amino-4-(4-cyanoanilino)-2-[4-(2-cyanoethyl)-2,6-dimethyl-phenoxy]-N-methyl-benzamide；5-amino-4-(4-cyanoanilino)-2-[4-(2-cyanoethyl)-2,6-dimethylphenoxy]-N-methylbenzamide
• CAS: 1393736-21-4
• 化学式: C₂₆H₂₅N₅O₂
• 分子量: 439.517
• InChiKey: MFHNFITUWQJMEV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  124
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-(4''-cyanoethyl-2'',6''-dimethylphenoxy)-N1-(4'-cyanophenyl)-4-(N-methyl-carbamoyl)-1,2-phenylenediamine 、 原甲酸三乙酯 在 盐酸 作用下， 以 乙醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以81%的产率得到6-[4-(2-cyanoethyl)-2,6-dimethyl-phenoxy]-1-(4-cyanophenyl)-N-methyl-benzimidazole-5-carboxamide
  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：

  N1-(4'-cyanophenyl)-5-(4''-(2-cyanovinyl)-2'',6''-dimethylphenoxy)-4-methylcarbamoyl-2-nitroaniline 在 5% Pd/C 、 氢气 作用下， 以 乙醇 为溶剂， 以65.9%的产率得到5-(4''-cyanoethyl-2'',6''-dimethylphenoxy)-N1-(4'-cyanophenyl)-4-(N-methyl-carbamoyl)-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

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
• Design, Synthesis, and Preclinical Evaluations of Novel 4-Substituted 1,5-Diarylanilines as Potent HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) Drug Candidates
  作者：Lian-Qi Sun、Lei Zhu、Keduo Qian、Bingjie Qin、Li Huang、Chin Ho Chen、Kuo-Hsiung Lee、Lan Xie

  DOI：10.1021/jm3007678

  日期：2012.8.23

  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.