5-tert-butyl-2-methyl-4-thiocyanatophenol | 207737-07-3

• 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-tert-butyl-2-methyl-4-thiocyanatophenol
• 英文别名: 5-tert-Butyl-2-methyl-4-thiocyanato-phenol；(2-tert-butyl-4-hydroxy-5-methylphenyl) thiocyanate
• CAS: 207737-07-3
• 化学式: C₁₂H₁₅NOS
• 分子量: 221.323
• InChiKey: BJAXARBQKRLWEV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  69.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-tert-butyl-2-methyl-4-thiocyanatophenol 在 potassium dihydrogenphosphate 、 caesium carbonate 、 三乙胺 、 1,4-二巯基-2,3-丁二醇 作用下， 以 四氯化碳 、 乙醇 、 乙腈 为溶剂， 生成 toluene-4-thiosulfonic acid S-(2-tert-butyl-4-dimethylsulfamoyloxy-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
• 作为产物：
  描述：

  5-(1,1-二甲基乙基)-2-甲基苯胺 在 盐酸 、 sodium nitrate 、 硫酸 、 溴 、 sodium bromide 作用下， 生成 5-tert-butyl-2-methyl-4-thiocyanatophenol
  参考文献：
  名称：

  5，6-二氢-4-羟基-2-吡喃酮类作为HIV-1蛋白酶抑制剂的合成：极性对抗病毒活性的深远影响。

  摘要：

  DOI：

  10.1021/jm970522y

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。
• Nonpeptidic HIV protease inhibitors: 6-alkyl-5,6-dihydropyran-2-ones possessing a novel and achiral 3-(2-t-butyl-5-methyl-4-sulfamate)phenylthio moiety
  作者：J.V.N Vara Prasad、Larry J Markoski、Fred E Boyer、John M Domagala、Edmund L Ellsworth、Christopher Gajda、Susan E Hagen、Bradley D Tait、Elizabeth A Lunney、Peter J Tummino、Donna Ferguson、Tod Holler、Donald Hupe、Carolyn Nouhan、Stephen J Gracheck、Steven VanderRoest、James Saunders、K Iyer、M Sinz

  DOI：10.1016/s0960-894x(99)00360-1

  日期：1999.8

  Dihydropyran-Zones possessing a sulfamate moiety at the 4-position of the thiophenyl ring were designed to reach S-3' pocket of the HIV protease. Synthetic routes for the preparation of thiotosylates possessing 3-(2-t-butyl-5-methyl-4-sulfamate) phenylthio moiety were established. SAR of various sulfamate analogs including HIV protease binding affinities, antiviral activities and therapeutic indices will be described. (C) 1999 Elsevier Science Ltd. All rights reserved.
• 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