3-[1-(Cyclohexylthio)-3,3-dimethylbutyl]-4-hydroxy-6-phenyl-2H-pyran-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃
• 英文名称: 3-[1-(Cyclohexylthio)-3,3-dimethylbutyl]-4-hydroxy-6-phenyl-2H-pyran-2-one
• 英文别名: 3-(1-Cyclohexylsulfanyl-3,3-dimethyl-butyl)-4-hydroxy-6-phenyl-pyran-2-one；3-(1-cyclohexylsulfanyl-3,3-dimethylbutyl)-4-hydroxy-6-phenylpyran-2-one
• 化学式: C₂₃H₃₀O₃S
• 分子量: 386.555
• InChiKey: XOMLSGLFNOYRSP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  71.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  环己硫醇 、 4-羟基-6-苯基吡喃-2-酮 、 3,3-二甲基丁醛 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 生成 3-[1-(Cyclohexylthio)-3,3-dimethylbutyl]-4-hydroxy-6-phenyl-2H-pyran-2-one
  参考文献：
  名称：

  Pyrone derivatives as protease inhibitors and antiviral agents

  摘要：

  本发明涉及新颖的三取代和四取代吡喃酮及相关结构，能有效抑制HIV天冬氨酸蛋白酶，阻止HIV的感染性。这些吡喃酮衍生物在开发治疗细菌和病毒感染以及疾病，包括艾滋病的疗法中是有用的。本发明还涉及多功能吡喃酮及相关结构的合成方法。

  公开号：

  US05808062A1

文献信息

• Nonpeptidic Potent HIV-1 Protease Inhibitors: (4-Hydroxy-6-phenyl-2-oxo-2H-pyran-3-yl)thiomethanes That Span P1-P2' Subsites in a Unique Mode of Binding
  作者：J. V. N. Vara Prasad、Kimberly S. Para、Peter J. Tummino、Donna Ferguson、Thomas J. McQuade、Elizabeth A. Lumney、Stephen T. Rapundalo、Brain L. Batley、Gary Hingorani

  DOI：10.1021/jm00006a007

  日期：1995.3

  Using molecular modeling and the information derived from the X-ray crystal structure of HIV-1 protease (HIV PR) complexed with the pyran-2-one 1, a series of (4-hydroxy-6-phenyl-2-oxo-2H-pyran-3-yl)thiomethanes was designed and analyzed as novel, nonpeptidic inhibitors of HIV PR. Structure-activity studies led to the discovery of inhibitor 19 having (RS)-1-(cyclopentylthio)-3-methylbutyl functionalization at the C-3 position, which exhibited a K-c of 33 nM. A X-ray crystallographic structure of 19 bound to HIV PR showed that structural water-301 (inhibitor-flap-bridging water) was displaced by the inhibitor. Interestingly, the enol moiety of the pyran-2-one formed a hydrogen bond directly with Asp125 and with Asp25 via a bridging water molecule, thus illustrating a unique mode of active site binding by an HIV PR inhibitor. The pendant cyclopentyl and isobutyl groups of 19 occupied the S-1' and S-2' binding sites, respectively, whereas the 6-phenyl group occupied a region in between the S-1 and S-3 pockets of HIV PR. Selected compounds were tested for antiviral activity on H9 cells infected with HIV-1(IIIb). A correlation between enzymatic activity and antiviral activity was not found in this series. The best antiviral compound in this series, 18, contained (RS)-3-[cyclopentyl(cyclopentylthio )methyl] functionalization at the C-3 position of the pyran-2-one ring and exhibited a CIC50 of 14 mu M and TC50 of 70 mu M. These studies demonstrate that potent enzyme inhibition can be achieved by inhibitors that span only three subsites.
• PYRONE DERIVATIVES AS PROTEASE INHIBITORS AND ANTIVIRAL AGENTS
  申请人：PARKE, DAVIS & COMPANY

  公开号：EP0729465A1

  公开（公告）日：1996-09-04
• US5808062A
  申请人：——

  公开号：US5808062A

  公开（公告）日：1998-09-15
• US6005103A
  申请人：——

  公开号：US6005103A

  公开（公告）日：1999-12-21
• [EN] PYRONE DERIVATIVES AS PROTEASE INHIBITORS AND ANTIVIRAL AGENTS<br/>[FR] DERIVES DE LA PYRONE EN TANT QU'INHIBITEURS DE LA PROTEASE ET AGENTS ANTIVIRAUX
  申请人：PARKE, DAVIS & COMPANY

  公开号：WO1995014013A1

  公开（公告）日：1995-05-26

  (EN) The present invention relates to novel tri- and tetrasubstituted pyrones and related structures which potently inhibit the HIV aspartyl protease blocking HIV infectivity. The pyrone derivatives are useful in the development of therapies for the treatment of bacterial and viral infections and diseases, including AIDS. The present invention is also directed to methods of synthesis of multifunctionalized pyrones and of related structures.(FR) La présente invention se rapporte à des nouvelles pyrones trisubstituées et tétrasubstituées ainsi qu'à leurs structures associées, qui inhibent puissamment l'aspartyle protéase du VIH en bloquant le pouvoir infectant du VIH. Ces dérivés de la pyrone sont utiles dans le développement des thérapies destinées au traitement des infections et maladies bactériennes et virales, notamment le SIDA. La présente invention se rapporte également à des procédés de synthèse de pyrones multifonctionnalisées et de structures apparentées.