4-cyanobenzenesulfonic acid 5-tert-butyl-2-methyl-4-(toluene-4-sulfonylsulfanyl)-phenyl ester | 263843-23-8

• 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: 4-cyanobenzenesulfonic acid 5-tert-butyl-2-methyl-4-(toluene-4-sulfonylsulfanyl)-phenyl ester
• 英文别名: [5-Tert-butyl-2-methyl-4-(4-methylphenyl)sulfonylsulfanylphenyl] 4-cyanobenzenesulfonate
• CAS: 263843-23-8
• 化学式: C₂₅H₂₅NO₅S₃
• 分子量: 515.675
• InChiKey: WMJRBIWGRKCQQE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 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：
  143
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-cyanobenzenesulfonic acid 5-tert-butyl-2-methyl-4-(toluene-4-sulfonylsulfanyl)-phenyl ester 在 盐酸 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 生成 4-cyanobenzenesulfonic acid 5-tert-butyl-4-{4-hydroxy-6-[2-(4-aminophenyl)ethyl]-6-isopropyl-2-oxo-5,6-dihydro-2H-pyran-3-ylsulfanyl}-2-methyl-phenyl ester hydrochloride
  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：

  4-叔丁基-1-甲基-2-硝基苯 在 镍 吡啶 、 potassium dihydrogenphosphate 、 氢气 、 溴 、 三乙胺 、 sodium bromide 、 sodium nitrite 、 1,4-二巯基-2,3-丁二醇 作用下， 以 甲醇 、 四氯化碳 、 乙醚 、 乙醇 为溶剂， 5.0~70.0 ℃ 、358.54 kPa 条件下， 反应 20.0h， 生成 4-cyanobenzenesulfonic acid 5-tert-butyl-2-methyl-4-(toluene-4-sulfonylsulfanyl)-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

文献信息

• Inhibitors of hepatitis C virus RNA-dependent RNA polymerase, and compositions and treatments using the same
  申请人：Agouron Pharmaceuticals, Inc.

  公开号：US20040023958A1

  公开（公告）日：2004-02-05

  Compounds of formula I are hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) inhibitors, and are useful in therapeutic and prophylactic treatment of persons infected with hepatitis C virus. 1

  式 I 的化合物是丙型肝炎病毒（HCV）RNA 依赖性 RNA 聚合酶（RdRp）抑制剂，可用于丙型肝炎病毒感染者的治疗和预防。 1
• US7115658B2
  申请人：——

  公开号：US7115658B2

  公开（公告）日：2006-10-03
• 5,6-Dihydropyran-2-ones Possessing Various Sulfonyl Functionalities:  Potent Nonpeptidic Inhibitors of HIV Protease
  作者：Frederick E. Boyer、J. V. N. Vara Prasad、John M. Domagala、Edmund L. Ellsworth、Christopher Gajda、Susan E. Hagen、Larry J. Markoski、Bradley D. Tait、Elizabeth A. Lunney、Alexander Palovsky、Donna Ferguson、Neil Graham、Tod Holler、Donald Hupe、Carolyn Nouhan、Peter J. Tummino、A. Urumov、Eric Zeikus、Greg Zeikus、Stephen J. Gracheck、James M. Sanders、Steven VanderRoest、Joanne Brodfuehrer、Krishna Iyer、Michael Sinz、Sergei V. Gulnik、John W. Erickson

  DOI：10.1021/jm990281p

  日期：2000.3.1

  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.