toluene-4-thiosulfonic acid S-(4-amino-2-tert-butyl-5-methylphenyl) ester | 207737-29-9

• 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-(4-amino-2-tert-butyl-5-methylphenyl) ester
• 英文别名: Toluene-4-thiosulfonic acid S-(4-amino-2-tert-butyl-5-methyl-phenyl) ester；5-tert-butyl-2-methyl-4-(4-methylphenyl)sulfonylsulfanylaniline
• CAS: 207737-29-9
• 化学式: C₁₈H₂₃NO₂S₂
• 分子量: 349.518
• InChiKey: KOBLYIJMXVVTNS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  93.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  toluene-4-thiosulfonic acid S-(4-amino-2-tert-butyl-5-methylphenyl) ester 在 吡啶 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (+-)-Methanesulfonamide, N-(4-((5,6-dihydro-4-hydroxy-6-(2-(4-hydroxyphenyl)ethyl)-6-methyl-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：

  4-叔丁基甲苯 在 palladium on activated charcoal 盐酸 、 sodium hydroxide 、 KH₂PO₄ buffer 、 DL-dithiothreitol 、 硫酸 、 氢气 、 溴 、 硝酸 、 三乙胺 、 sodium bromide 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 生成 toluene-4-thiosulfonic acid S-(4-amino-2-tert-butyl-5-methylphenyl) ester
  参考文献：
  名称：

  Nonpeptidic HIV protease inhibitors: 6-alkyl-5, 6-dihydropyran-2-ones possessing achiral 3-(4-amino/carboxamide-2-t-butyl, 5-methylphenyl thio) moiety: Antiviral activities and pharmacokinetic properties

  摘要：

  Dihydropyran-2-ones possessing amino and carboxamide functionalities on 3-SPh (2-tert-butyl, 5-methyl) ring were synthesized and evaluated for their antiviral activities. Both the enantiomers of inhibitor 15 were synthesized. The in vitro resistance profile, inhibitory activities against cytochrome P450 isozymes and pharmacokinetic properties of inhibitor 15S will be discussed.

  DOI：

  10.1016/s0960-894x(99)00237-1

文献信息

• HIV protease inhibitors
  申请人：Warner-Lambert Company

  公开号：US06528510B1

  公开（公告）日：2003-03-04

  The present invention relates to novel dihydropyrones with tethered heterocycles having improved pharmacologic properties which potently inhibit the HIV aspartyl protease blocking HIV infectivity. The dihydropyrones are useful in the development of therapies for the treatment of viral infections and diseases, including AIDS. The present invention is also directed to methods of synthesis of the dihydropyrones and intermediates useful in the preparation of the final compounds.

  本发明涉及具有改进药理特性的新型带有连环杂环的二氢吡喃，能有效抑制HIV天冬氨酸蛋白酶，阻断HIV的感染性。这些二氢吡喃在开发治疗病毒感染和疾病，包括艾滋病的疗法方面是有用的。本发明还涉及合成这些二氢吡喃的方法，以及在制备最终化合物中有用的中间体。
• [EN] INHIBITORS OF HEPATITIS C VIRUS RNA-DEPENDENT RNA POLYMERASE, AND COMPOSITIONS AND TREATMENTS USING THE SAME<br/>[FR] INHIBITEURS DE L'ARN POLYMERASE ARN-DEPENDANTE DU VIRUS DE L'HEPATITE C ET COMPOSITIONS ET TRAITEMENTS UTILISANT CETTE POLYMERASE
  申请人：PFIZER

  公开号：WO2003095441A1

  公开（公告）日：2003-11-20

  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.

  化合物的化学式（I）是丙型肝炎病毒（HCV）RNA依赖性RNA聚合酶（RdRp）抑制剂，对感染丙型肝炎病毒的人进行治疗和预防性治疗具有用处。
• Dihydropyrones with improved antiviral activity
  申请人：Warner-Lambert Company

  公开号：US05834506A1

  公开（公告）日：1998-11-10

  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位置聪明地放置某些极性取代基来改善6,6-二取代-5,6-二氢吡喃-2-酮的抗病毒活性。增强细胞活性的相同取代基也减少细胞毒性，进一步增强这些药物作为抗病毒剂的理想性能。
• Hepatitis C virus (HCV) NS5B RNA polymerase and mutants thereof
  申请人：Agouron Pharmaceuticals, Inc.

  公开号：EP1256628A9

  公开（公告）日：2003-04-16

  The present invention generally relates to viral RNA polymerases, which are essential to viral reproduction and propagation in a host. Viral RNA polymerases are known to play a role in the replication of the virus once it has infected its host. The present invention relates to mutants of native Hepatitis C Virus (HCV) RNA polymerase, said mutants imparting improved crystallization properties of the enzyme and enzyme/compound complexes. The present invention also relates to the isolation and identification of an allosteric binding cleft within the HCV NS5B RNA polymerase and its use in the discovery, identification, and characterization of inhibitors of same.

  本发明通常涉及病毒RNA聚合酶，该酶对于病毒在宿主体内的复制和传播至关重要。已知病毒RNA聚合酶在病毒感染宿主后的复制中发挥作用。本发明涉及天然丙型肝炎病毒（HCV）RNA聚合酶的突变体，该突变体赋予酶和酶/化合物复合物改进的结晶性能。本发明还涉及在HCV NS5B RNA聚合酶中分离和鉴定一个变构结合裂隙及其在发现、鉴定和表征其抑制剂方面的应用。
• Hepatitis c virus (hcv) ns5b rna polymerase and mutants thereof
  申请人：Agouron Pharmaceuticals, Inc.

  公开号：EP1256628A2

  公开（公告）日：2002-11-13

  The present invention generally relates to viral RNA polymerases, which are essential to viral reproduction and propagation in a host. Viral RNA polymerases are known to play a role in the replication of the virus once it has infected its host. The present invention relates to mutants of native Hepatitis C Virus (HCV) RNA polymerase, said mutants imparting improved crystallization properties of the enzyme and enzyme/compound complexes. The present invention also relates to the isolation and identification of an allosteric binding cleft within the HCV NS5B RNA polymerase and its use in the discovery, identification, and characterization of inhibitors of same.

  本发明一般涉及病毒 RNA 聚合酶，它对病毒在宿主体内的繁殖和传播至关重要。 已知病毒 RNA 聚合酶在病毒感染宿主后的复制过程中发挥作用。 本发明涉及原生丙型肝炎病毒（HCV）RNA 聚合酶的突变体，所述突变体可改善酶和酶/化合物复合物的结晶特性。 本发明还涉及分离和鉴定 HCV NS5B RNA 聚合酶内的异生结合裂隙，并将其用于发现、鉴定和表征其抑制剂。