4-hydroxy-6-[2-(4-hydroxy-phenyl)ethyl]-6-phenyl-5,6-dihydro-pyran-2-one | 207736-95-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃
• 英文名称: 4-hydroxy-6-[2-(4-hydroxy-phenyl)ethyl]-6-phenyl-5,6-dihydro-pyran-2-one
• 英文别名: 4-Hydroxy-6-[2-(4-hydroxy-phenyl)-ethyl]-6-phenyl-5,6-dihydro-pyran-2-one；4-hydroxy-2-[2-(4-hydroxyphenyl)ethyl]-2-phenyl-3H-pyran-6-one
• CAS: 207736-95-6
• 化学式: C₁₉H₁₈O₄
• 分子量: 310.35
• InChiKey: SQSGHPOITYJTOQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-hydroxy-6-[2-(4-hydroxy-phenyl)ethyl]-6-phenyl-5,6-dihydro-pyran-2-one 、 2-tert-butyl-5-methyl-phenyl-p-toluenethiosulfonate 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 5-[(2-Tert-butyl-5-methylphenyl)sulfanyl]-6-hydroxy-2-[2-(4-hydroxyphenyl)ethyl]-2-phenyl-2,3-dihydro-4h-pyran-4-one
  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
• 作为产物：
  描述：

  3-(4-羟基苯基)-1-苯基丙烷-1-酮 、 乙酰乙酸甲酯 在 sodium hydroxide 、 正丁基锂 、 sodium hydride 作用下， 生成 4-hydroxy-6-[2-(4-hydroxy-phenyl)ethyl]-6-phenyl-5,6-dihydro-pyran-2-one
  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
• 作为试剂：
  描述：

  7-[4-(Tert-butyl-dimethyl-silanyloxy)-phenyl]-5-hydroxy-3-oxo-5-phenyl-heptanoic acid methyl ester 、 四丁基氟化铵 、 、 Sodium hydroxide tetrahydrofuran 在 4-hydroxy-6-[2-(4-hydroxy-phenyl)ethyl]-6-phenyl-5,6-dihydro-pyran-2-one 、 silica gel 、 methanol-dichloromethane 作用下， 以 四氢呋喃 为溶剂， 生成 4-hydroxy-6-[2-(4-hydroxy-phenyl)ethyl]-6-phenyl-5,6-dihydro-pyran-2-one
  参考文献：
  名称：

  Dihydropyrones with improved antiviral activity

  摘要：

  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。

  公开号：

  US06046355A1

文献信息

• Nonpeptidic HIV protease inhibitors possessing excellent antiviral activities and therapeutic indices. PD 178390: a lead HIV protease inhibitor
  作者：J.V.N. Vara Prasad、Frederick E. Boyer、John M. Domagala、Edmund L. Ellsworth、Christopher Gajda、Harriet W. Hamilton、Susan E. Hagen、Larry J. Markoski、Bruce A. Steinbaugh、Bradley D. Tait、Christine Humblet、Elizabeth A. Lunney、Alexander Pavlovsky、John R. Rubin、Donna Ferguson、Neil Graham、Tod Holler、Donald Hupe、Carolyn Nouhan、Peter J. Tummino、A. Urumov、Eric Zeikus、Greg Zeikus、Stephen J. Gracheck、James M. Saunders、Steven VanderRoest、Joanne Brodfuehrer、K. Iyer、M. Sinz、Sergei V. Gulnik、John W. Erickson

  DOI：10.1016/s0968-0896(99)00215-1

  日期：1999.12

  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.
• 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