toluene-4-thiosulfonic acid S-[2-tert-butyl-4-(3-cyanobenzenesulfonylamino)-5-methyl-phenyl] ester | 263843-13-6

• 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: toluene-4-thiosulfonic acid S-[2-tert-butyl-4-(3-cyanobenzenesulfonylamino)-5-methyl-phenyl] ester
• 英文别名: N-[5-tert-butyl-2-methyl-4-(4-methylphenyl)sulfonylsulfanylphenyl]-3-cyanobenzenesulfonamide
• CAS: 263843-13-6
• 化学式: C₂₅H₂₆N₂O₄S₃
• 分子量: 514.69
• InChiKey: NCIKNEUVNRDSPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  146
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-hydroxy-6-[2-(4-hydroxy-phenyl)ethyl]-6-isopropyl-5,6-dihydro-pyran-2-one 、 toluene-4-thiosulfonic acid S-[2-tert-butyl-4-(3-cyanobenzenesulfonylamino)-5-methyl-phenyl] ester 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以51%的产率得到(+-)-Benzenesulfonamide, 3-cyano-N-(4-((5,6-dihydro-4-hydroxy-6-(2-(4-hydroxyphenyl)ethyl)-6-(1-methylethyl)-2-oxo-2H-pyran-3-yl)thio)-5-(1,1-dimethylethyl)-2-methylphenyl)-
  参考文献：
  名称：

  5,6-Dihydropyran-2-ones Possessing Various Sulfonyl Functionalities:  Potent Nonpeptidic Inhibitors of HIV Protease

  摘要：

  On the basis of previous SAR findings and molecular modeling studies, a series of compounds were synthesized which possessed various sulfonyl moieties substituted at the 4-position of the C-3 phenyl ring substituent of the dihydropyran-2-one ring system. The sulfonyl substituents were added in an attempt to fill the additional S-3' pocket and thereby produce increasingly potent inhibitors of the target enzyme. Racemic and enantiomerically resolved varieties of selected compounds were synthesized. All analogues in the study displayed decent binding affinity to HIV protease, and several compounds were shown to possess very good antiviral efficacy and safety margins. X-ray crystallographic structures confirmed that the sulfonamide and sulfonate moieties were filling the S3' pocket of the enzyme. However, the additional substituent did not provide improved enzymatic inhibitory or antiviral activity as compared to the resolved unsubstituted aniline. The addition of the sulfonyl moiety substitution does not appear to provide favorable pharamacokinectic parameters. Selected inhibitors were tested for antiviral activity in clinical isolates and exhibited similar antiviral activity against all of the HIV-1 strains tested as they did against the wild-type HIV-1, In addition, the inhibitors exhibited good antiviral efficacies against HIV-1 strains that displayed resistance to the currently marketed protease inhibitors.

  DOI：

  10.1021/jm990281p
• 作为产物：
  描述：

  3-氰基苯磺酰氯 、 toluene-4-thiosulfonic acid S-(4-amino-2-tert-butyl-5-methylphenyl) ester 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 以57%的产率得到toluene-4-thiosulfonic acid S-[2-tert-butyl-4-(3-cyanobenzenesulfonylamino)-5-methyl-phenyl] ester
  参考文献：
  名称：

  5,6-Dihydropyran-2-ones Possessing Various Sulfonyl Functionalities:  Potent Nonpeptidic Inhibitors of HIV Protease

  摘要：

  On the basis of previous SAR findings and molecular modeling studies, a series of compounds were synthesized which possessed various sulfonyl moieties substituted at the 4-position of the C-3 phenyl ring substituent of the dihydropyran-2-one ring system. The sulfonyl substituents were added in an attempt to fill the additional S-3' pocket and thereby produce increasingly potent inhibitors of the target enzyme. Racemic and enantiomerically resolved varieties of selected compounds were synthesized. All analogues in the study displayed decent binding affinity to HIV protease, and several compounds were shown to possess very good antiviral efficacy and safety margins. X-ray crystallographic structures confirmed that the sulfonamide and sulfonate moieties were filling the S3' pocket of the enzyme. However, the additional substituent did not provide improved enzymatic inhibitory or antiviral activity as compared to the resolved unsubstituted aniline. The addition of the sulfonyl moiety substitution does not appear to provide favorable pharamacokinectic parameters. Selected inhibitors were tested for antiviral activity in clinical isolates and exhibited similar antiviral activity against all of the HIV-1 strains tested as they did against the wild-type HIV-1, In addition, the inhibitors exhibited good antiviral efficacies against HIV-1 strains that displayed resistance to the currently marketed protease inhibitors.

  DOI：

  10.1021/jm990281p