toluene-4-thiosulfonic acid S-(2-tert-butyl-4-hydroxymethyl-5-methyl-phenyl) ester | 207737-06-2

• 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-hydroxymethyl-5-methyl-phenyl) ester
• 英文别名: Toluene-4-thiosulfonic acid S-(2-tert-butyl-4-hydroxymethyl-5-methylphenyl) ester；2-tert-butyl-4-hydroxymethyl-5-methyl-phenyl-p-toluenethiosulfonate；toluene-4-thiosulfonic acid S-(2-tert-butyl-4-hydroxymethyl-5-methyl-phenyl)ester；S-[2-Tert-butyl-4-(hydroxymethyl)-5-methylphenyl] 4-methylbenzenesulfonothioate；[5-tert-butyl-2-methyl-4-(4-methylphenyl)sulfonylsulfanylphenyl]methanol
• CAS: 207737-06-2
• 化学式: C₁₉H₂₄O₃S₂
• 分子量: 364.53
• InChiKey: PAIDQJHQNXEBAN-UHFFFAOYSA-N

物化性质

• 沸点：
  515.4±60.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  88
• 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-(2-tert-butyl-4-hydroxymethyl-5-methyl-phenyl) ester 在 sodium hydroxide 、 potassium carbonate 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 6-[2-(4-aminophenyl)ethyl]-3-(2-tert-butyl-4-hydroxymethyl-5-methyl-phenylsulfanyl)-4-hydroxy-6-phenyl-5,6-dihydro-pyran-2-one
  参考文献：
  名称：

  Nonpeptidic HIV protease inhibitors possessing excellent antiviral activities and therapeutic indices. PD 178390: a lead HIV protease inhibitor

  摘要：

  With the insight generated by the availability of X-ray crystal structures of various 5,6-dihydropyran-2-ones bound to HIV PR, inhibitors possessing various alkyl groups at the 6-position of 5,6-dihydropyran-2-one ring were synthesized. The inhibitors possessing a 6-alkyl group exhibited superior antiviral activities when compared to 6-phenyl analogues. Antiviral efficacies were further improved upon introduction of a polar group (hydroxyl or amino) on the 4-position of the phenethyl moiety as well as the polar group (hydroxymethyl) on the 3-(tert-butyl-5-methyl-phenylthio) moiety. The polar substitution is also advantageous for decreasing toxicity, providing inhibitors with higher therapeutic indices. The best inhibitor among this series, (S)-6-[2-(4-aminophenyl)-ethyl]-(3-(2-tert-butyl-5-methyl-phenylsulfa nyl)-4-hydroxy-6-isopropyl-5,6-dihydro-pyran-2-one (34S), exhibited an EC50 of 200 nM with a therapeutic index of > 1000. More importantly, these non-peptidic inhibitors, 16S and 34S, appear to offer little cross-resistance to the currently marketed peptidomimetic PR inhibitors. The selected inhibitors tested in vitro against mutant HIV PR showed a very small increase in binding affinities relative to wild-type HIV PR. Cmax and absolute bioavailability of 34S were higher and half-life and time above EC95 were longer compared to 16S. Thus 34S, also known as PD 178390, which displays good antiviral efficacy, promising pharmacokinetic characteristics and favorable activity against mutant enzymes and CYP3A4, has been chosen for further preclinical evaluation.

  DOI：

  10.1016/s0968-0896(99)00215-1
• 作为产物：
  描述：

  6-叔丁基间甲酚 在 吡啶 、 正丁基锂 、 硫酸 、 溴 、 sodium hydride 、 二异丁基氢化铝 作用下， 以 四氢呋喃 、 四氯化碳 、 二氯甲烷 为溶剂， 生成 toluene-4-thiosulfonic acid S-(2-tert-butyl-4-hydroxymethyl-5-methyl-phenyl) ester
  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

• 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。
• A CONTINUOUS PROCEDURE FOR PREPARATION OF para FUNCTION ALIZED AROMATIC THIOLS USING NEWMAN-KWART CHEMISTRY
  作者：Sechoing Lin、Brian Moon、Kenneth T. Porter、Craig A. Rossman、Thomas Zennie、James Wemple

  DOI：10.1080/00304940009355949

  日期：2000.12

  3-Arylthjo-4-hydroxy-5,6-dIhydropyrones such as CI1029 (8a) and PD 190497 (8b) are members of a new class of HIV protease inhibitors which are nonpeptidic, competitive, reversible inhibitors of the protease enzyme.'.' The 3-arylthio-4-hydroxy-5,6-dihydropyrones enjoy low cross resistance relative to currently marketed peptidomimetic protease inhibitors. S-Arylsulfonyl derivatives (6) of 2-tert-but

  3-Arylthjo-4-hydroxy-5,6-dIhydropyrones 如 CI1029 (8a) 和 PD 190497 (8b) 是一类新的 HIV 蛋白酶抑制剂的成员，它们是蛋白酶的非肽类、竞争性、可逆抑制剂。 ' 3-芳硫基-4-羟基-5,6-二氢吡喃酮相对于目前市售的拟肽蛋白酶抑制剂具有较低的交叉抗性。2-叔丁基-4-羟甲基-5-甲基苯硫酚 (5) 的 S-芳基磺酰基衍生物 (6) 是合成 PD 190497 和 CI-1029 所需的关键中间体。在此过程中，甲苯磺酰基在 6 与烯醇活化的亲核中心的偶联反应中被置换为离去基团，该中心在适当取代的 4-羟基-5,6-二氢吡喃酮（如 7）中发现。 2.3
• 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