3,3-diethoxy-6-methyl-4-oxo-3,4-dihydro-2H-pyran-5-carboxylic acid | 944269-42-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃
• 英文名称: 3,3-diethoxy-6-methyl-4-oxo-3,4-dihydro-2H-pyran-5-carboxylic acid
• 英文别名: 3,3-diethoxy-6-methyl-4-oxo-2H-pyran-5-carboxylic acid
• CAS: 944269-42-5
• 化学式: C₁₁H₁₆O₆
• 分子量: 244.244
• InChiKey: WKCJCCOIXVYNPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  82.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3,3-diethoxy-6-methyl-4-oxo-3,4-dihydro-2H-pyran-5-carboxylic acid 在 甲酸 、 三乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 5-hydroxy-N,2-dimethyl-4-oxo-4H-pyran-3-carboxamide
  参考文献：
  名称：

  [EN] COMPOSITIONS AND METHODS FOR INHIBITING INFLUENZA RNA POLYMERASE PA ENDONUCLEASE
  [FR] COMPOSITIONS ET PROCÉDÉS POUR INHIBER L'ENDONUCLÉASE DE LA PA DE L'ARN POLYMÉRASE DE LA GRIPPE

  摘要：

  其中提供了金属酶抑制剂，例如流感A病毒RNA依赖性RNA聚合酶PA亚基内切酶的抑制剂，以及其合成和使用方法。

  公开号：

  WO2017156194A1
• 作为产物：
  描述：

  3-溴-2,2-二乙氧基丙酸 在 吡啶 、 sodium hydride 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 18.0h， 生成 3,3-diethoxy-6-methyl-4-oxo-3,4-dihydro-2H-pyran-5-carboxylic acid
  参考文献：
  名称：

  基于片段的流感核酸内切酶抑制剂的鉴定

  摘要：

  流感病毒每年造成数百万例严重疾病。疫苗效力的逐年变化，加上新出现的耐药性，有必要开发用于治疗流感感染的新药。一种有吸引力的靶标是RNA依赖性RNA聚合酶PA亚基。本文中，我们报道了从金属结合药效团（MBP）库筛选中鉴定出的先导化合物衍生的流感PA核酸内切酶抑制剂的发展。发现焦果烯酸及其衍生物是核酸内切酶的有效抑制剂。在建模和先前报道的结构数据的指导下，从MBP命中中精心制作了分子的几个子库。建立了结构与活动的关系，使用片段增长和片段合并策略设计和合成了更有效的分子。这种方法最终导致了带有IC的铅化合物的开发50值为14 nM，显示MDCK细胞中针对H1N1流感病毒的EC 50值为2.1μM。

  DOI：

  10.1021/acs.jmedchem.6b00628

文献信息

• Compositions and methods for inhibiting influenza RNA polymerase PA endonuclease
  申请人：The Regents of the University of California

  公开号：US10889556B2

  公开（公告）日：2021-01-12

  There are provided inter alia metalloenzyme inhibitors, such as inhibitors of influenza A RNA dependent RNA polymerase PA subunit endonuclease, and methods of synthesis and use of the same.

  除其他外，还提供了金属酶抑制剂，例如甲型流感 RNA 依赖性 RNA 聚合酶 PA 亚基内切酶抑制剂，以及合成和使用这些抑制剂的方法。
• Synthesis of hydroxypyrone- and hydroxythiopyrone-based matrix metalloproteinase inhibitors: Developing a structure–activity relationship
  作者：Yi-Long Yan、Melissa T. Miller、Yuchen Cao、Seth M. Cohen

  DOI：10.1016/j.bmcl.2009.02.044

  日期：2009.4

  The zinc(II)-dependent matrix metalloproteinases (MMPs) are associated with a variety of diseases. Development of inhibitors to modulate MMP activity has been an active area of investigation for therapeutic development. Hydroxypyrones and hydroxythiopyrones are alternative zinc-binding groups (ZBGs) that, when combined with peptidomimetic backbones, comprise a novel class of MMP inhibitors (MMPi). In this report, a series of hydroxypyrone- and hydroxythiopyrone-based MMPi with aryl backbones at the 2-, 5-, and 6- positions of the hydroxypyrone ring have been synthesized. Synthetic routes for developing inhibitors with substituents at two of these positions (so-called double-handed inhibitors) are also explored. The MMP inhibition profiles and structure-activity relationship of synthesized hydroxypyrones and hydroxythiopyrones have been analyzed. The results here show that the ZBG, the position of the backbone on the ZBG, and the nature of the linker between the ZBG and backbone are critical for MMPi activities. (C) 2009 Elsevier Ltd. All rights reserved.
• Efficient Synthesis of 5-Amido-3-hydroxy-4-pyrones as Inhibitors of Matrix Metalloproteinases
  作者：Yi-Long Yan、Seth M. Cohen

  DOI：10.1021/ol0707665

  日期：2007.6.1

  3-Hydroxy-4-pyrones are a class of important metal chelators with versatile medicinal applications. An efficient pathway for the preparation of new 5-amido-3-hydroxy-4-pyrone derivatives has been developed. The synthesized 5-amido-3-hydroxy-4-pyrones have been evaluated as inhibitors of matrix metalloproteinases.
• COMPOSITIONS AND METHODS FOR INHIBITING INFLUENZA RNA POLYMERASE PA ENDONUCLEASE
  申请人：The Regents of the University of California

  公开号：US20190106398A1

  公开（公告）日：2019-04-11

  There are provided inter alia metalloenzyme inhibitors, such as inhibitors of influenza A RNA dependent RNA polymerase PA subunit endonuclease, and methods of synthesis and use of the same.