3,5,7-trimethoxyisobenzofuran-1(3H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: 3,5,7-trimethoxyisobenzofuran-1(3H)-one
• 英文别名: 3,5,7-trimethoxy-3H-2-benzofuran-1-one
• 化学式: C₁₁H₁₂O₅
• 分子量: 224.213
• InChiKey: CZNYBUZEEYZAKA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3,5,7-trimethoxyisobenzofuran-1(3H)-one 在 lithium aluminium tetrahydride 、 bis[dichloro(pentamethylcyclopentadienyl)iridium(III)] 、 palladium 10% on activated carbon 、 氢气 、 碳酸氢钠 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， -78.0~110.0 ℃ 、101.33 kPa 条件下， 反应 88.0h， 生成 2-(2,4-Dimethoxyphenyl)sulfonyl-4,6-dimethoxy-1,3-dihydroisoindole
  参考文献：
  名称：

  [EN] INHIBITORS OF MITOCHONDRIAL PYRUVATE DEHYDROGENASE KINASE ISOFORMS 1-4 AND USES THEREOF
  [FR] INHIBITEURS D'ISOFORMES DE PYRUVATE DÉSHYDROGÉNASE KINASE MITOCHONDRIALES 1-4 ET LEURS UTILISATIONS

  摘要：

  公开号：

  WO2015089360A8

文献信息

• Inhibitors of mitochondrial pyruvate dehydrogenase kinase isoforms 1-4 and uses thereof
  申请人：The Board of Regents of the University of Texas System

  公开号：US10167258B2

  公开（公告）日：2019-01-01

  The present disclosure relates to the identification of PDK inhibitors and their use in the treatment of diseases such as diabetes, cardiovascular disease and cancer. The invention relates to the development of robust PDK inhibitors that can be used to improve glucose metabolism and correct metabolic dysfunction in vivo. Based on the unique structural features present in the ATP-binding pocket of PDK2, a single functional-group change was made in a known Hsp90 inhibitor that binds to the corresponding pocket of the latter protein from the GHKL family. This approach efficiently converted the Hsp90 inhibitor to a highly specific inhibitor for all PDK isoforms. These final PDK inhibitors of this series robustly augments PDC activity with reduced phosphorylation in tissues.

  本公开涉及 PDK 抑制剂的鉴定及其在治疗糖尿病、心血管疾病和癌症等疾病中的应用。本发明涉及开发可用于改善葡萄糖代谢和纠正体内代谢功能障碍的强效 PDK 抑制剂。根据 PDK2 的 ATP 结合口袋中存在的独特结构特征，对已知的 Hsp90 抑制剂进行了单官能团改变，使其与 GHKL 家族后一种蛋白质的相应口袋结合。这种方法有效地将 Hsp90 抑制剂转变成了一种针对所有 PDK 同工酶的高度特异性抑制剂。该系列的最后几种 PDK 抑制剂可增强 PDC 的活性，同时降低组织中的磷酸化。
• INHIBITORS OF MITOCHONDRIAL PYRUVATE DEHYDROGENASE KINASE ISOFORMS 1-4 AND USES THEREOF
  申请人：THE BOARD OF REGENTS OF THE UNIVERSITY OF TEXAS SYSTEM

  公开号：US20170001958A1

  公开（公告）日：2017-01-05

  The present disclosure relates to the identification of PDK inhibitors and their use in the treatment of diseases such as diabetes, cardiovascular disease and cancer. The invention relates to the development of robust PDK inhibitors that can be used to improve glucose metabolism and correct metabolic dysfunction in vivo. Based on the unique structural features present in the ATP-binding pocket of PDK2, a single functional-group change was made in a known Hsp90 inhibitor that binds to the corresponding pocket of the latter protein from the GHKL family. This approach efficiently converted the Hsp90 inhibitor to a highly specific inhibitor for all PDK isoforms. These final PDK inhibitors of this series robustly augments PDC activity with reduced phosphorylation in tissues.
• [EN] INHIBITORS OF MITOCHNONDRIAL PYRUVATE DEHYDROGENASE KINASE ISOFORMS 1-4 AND USES THEREOF<br/>[FR] INHIBITEURS D'ISOFORMES DE PYRUVATE DÉSHYDROGÉNASE KINASE MITOCHONDRIALES 1-4 ET LEURS UTILISATIONS
  申请人：UNIV TEXAS

  公开号：WO2015089360A1

  公开（公告）日：2015-06-18

  The present disclosure relates to the identification of PDK inhibitors and their use in the treatment of diseases such as diabetes, cardiovascular disease and cancer. The invention relates to the development of robust PDK inhibitors that can be used to improve glucose metabolism and correct metabolic dysfunction in vivo. Based on the unique structural features present in the ATP-binding pocket of PDK2, a single functional-group change was made in a known Hsp90 inhibitor that binds to the corresponding pocket of the latter protein from the GHKL family. This approach efficiently converted the Hsp90 inhibitor to a highly specific inhibitor for all PDK isoforms. These final PDK inhibitors of this series robustly augments PDC activity with reduced phosphorylation in tissues.