[5-(1,1-dimethylethyl)-4-mercapto-2-methylphenyl]imidodicarbonic acid bis(1,1-dimethylethyl) ester | 207737-27-7

• 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-(1,1-dimethylethyl)-4-mercapto-2-methylphenyl]imidodicarbonic acid bis(1,1-dimethylethyl) ester
• 英文别名: [5-(1,1-Dimethylethyl)-4-mercapto-2-methylphenyl]-imidodicarbonic acid bis(1,1-dimethylethyl) ester；tert-butyl N-(5-tert-butyl-2-methyl-4-sulfanylphenyl)-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamate
• CAS: 207737-27-7
• 化学式: C₂₁H₃₃NO₄S
• 分子量: 395.563
• InChiKey: HBLGSUCDITXMMG-UHFFFAOYSA-N

物化性质

• 沸点：
  469.413±55.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.092±0.06 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  56.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [5-(1,1-dimethylethyl)-4-mercapto-2-methylphenyl]imidodicarbonic acid bis(1,1-dimethylethyl) ester 在 盐酸 、 三乙胺 作用下， 以 四氯化碳 、 二氯甲烷 为溶剂， 反应 0.67h， 生成 toluene-4-thiosulfonic acid S-(4-amino-2-tert-butyl-5-methylphenyl) 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 potassium dihydrogenphosphate 、 氢气 、 溴 、 sodium bromide 、 1,4-二巯基-2,3-丁二醇 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 为溶剂， 35.0~60.0 ℃ 、358.54 kPa 条件下， 反应 87.5h， 生成 [5-(1,1-dimethylethyl)-4-mercapto-2-methylphenyl]imidodicarbonic acid bis(1,1-dimethylethyl) 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

• Dihydropyrones with improved antiviral activity
  申请人：Warner-Lambert Company

  公开号：US06046355A1

  公开（公告）日：2000-04-04

  This invention pertains to improved antiviral activity of 6,6-disubstituted-5,6-dihydropyran-2-ones caused by judicious placement of certain polar substituents at the 3 and/or 6 positions. The same substituents which enhance the cellular activity also diminish cytotoxicity further enhancing the desirable properties of these agents as antivirals.

  本发明涉及通过在3和/或6位恰当地放置某些极性取代基，改善6,6-二取代-5,6-二氢吡喃-2-酮的抗病毒活性。这些增强细胞活性的相同取代基还降低了细胞毒性，进一步增强了这些化合物作为抗病毒药物的理想性能。
• DIHYDROPYRONES WITH IMPROVED ANTIVIRAL ACTIVITY
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0935597A2

  公开（公告）日：1999-08-18
• US5834506A
  申请人：——

  公开号：US5834506A

  公开（公告）日：1998-11-10
• US6046355A
  申请人：——

  公开号：US6046355A

  公开（公告）日：2000-04-04
• [EN] DIHYDROPYRONES WITH IMPROVED ANTIVIRAL ACTIVITY<br/>[FR] DIHYDROPYRONES A ACTIVITE ANTIVIRALE AMELIOREE
  申请人：——

  公开号：WO1998019997A2

  公开（公告）日：1998-05-14

  [EN] This invention pertains to improved antiviral activity of 6,6-disubstituted-5,6-dihydropyran-2-ones caused by judicious placement of certain polar substituents at the 3 and/or 6 positions. The same substituents which enhance the cellular activity also diminish cytotoxicity further enhancing the desirable properties of these agents as antivirals.
  [FR] La présente invention concerne une amélioration de l'activité antivirale de 5,6-dihydropyran-2-ones disubstitués en 6,6 obtenue grâce à une disposition judicieuse de substituants en positions 3 et/ou 6. Ces mêmes substituants qui renforcent l'activité cellulaire diminuent également la cytotoxicité, ce qui renforce encore plus les propriétés souhaitables de ces agents comme antiviraux.