(E)-6-(7-Cyano-4-hydroxy-6-methoxy-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-4-methyl-hex-4-enoic acid methyl ester | 182010-29-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异香豆素
• 英文名称: (E)-6-(7-Cyano-4-hydroxy-6-methoxy-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-4-methyl-hex-4-enoic acid methyl ester
• 英文别名: methyl (E)-6-(7-cyano-4-hydroxy-6-methoxy-3-oxo-1H-2-benzofuran-5-yl)-4-methylhex-4-enoate
• CAS: 182010-29-3
• 化学式: C₁₈H₁₉NO₆
• 分子量: 345.352
• InChiKey: AOWGDJONCLICGC-ONNFQVAWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (E)-6-(7-Cyano-4-hydroxy-6-methoxy-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-4-methyl-hex-4-enoic acid methyl ester 在 lithium hydroxide 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以20%的产率得到(E)-6-(7-carbamoyl-4-hydroxy-6-methoxy-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methyl-4-hexenoic acid
  参考文献：
  名称：

  Structure−Activity Relationships for Inhibition of Inosine Monophosphate Dehydrogenase by Nuclear Variants of Mycophenolic Acid

  摘要：

  Structure-activity relationships in the region of the phthalide ring of the inosine monophosphate dehydrogenase inhibitor mycophenolic acid have been explored. Replacement of the lactone ring with other cyclic moieties resulted in loss of potency, especially for larger groups. Replacement of the ring by acyclic substituents also indicated a strong sensitivity to steric bulk. A phenolic hydroxyl group, with an adjacent hydrogen bond acceptor, was found to be essential for high potency. The aromatic methyl group was essential for activity; the methoxyl group could be replaced by ethyl to give a compound with 2-4 times the potency of mycophenolic acid in vitro and in vivo.

  DOI：

  10.1021/jm9603633
• 作为产物：
  描述：

  5-methoxy 7-(prop-2-enyloxy)phthalide 在 吡啶 、 咪唑 、 ozone-containing oxygen 、 四(三苯基膦)钯 、 三甲基锍 、 四丁基氟化铵 、 溴 、 溶剂黄146 、 N,N-二乙基苯胺 、 锌 、 三甲基乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 97.17h， 生成 (E)-6-(7-Cyano-4-hydroxy-6-methoxy-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-4-methyl-hex-4-enoic acid methyl ester
  参考文献：
  名称：

  Structure−Activity Relationships for Inhibition of Inosine Monophosphate Dehydrogenase by Nuclear Variants of Mycophenolic Acid

  摘要：

  Structure-activity relationships in the region of the phthalide ring of the inosine monophosphate dehydrogenase inhibitor mycophenolic acid have been explored. Replacement of the lactone ring with other cyclic moieties resulted in loss of potency, especially for larger groups. Replacement of the ring by acyclic substituents also indicated a strong sensitivity to steric bulk. A phenolic hydroxyl group, with an adjacent hydrogen bond acceptor, was found to be essential for high potency. The aromatic methyl group was essential for activity; the methoxyl group could be replaced by ethyl to give a compound with 2-4 times the potency of mycophenolic acid in vitro and in vivo.

  DOI：

  10.1021/jm9603633

文献信息

• Structure−Activity Relationships for Inhibition of Inosine Monophosphate Dehydrogenase by Nuclear Variants of Mycophenolic Acid
  作者：Peter H. Nelson、Stephen F. Carr、Bruce H. Devens、Elsie M. Eugui、Fidencio Franco、Carlos Gonzalez、Ronald C. Hawley、David G. Loughhead、David J. Milan、Eva Papp、John W. Patterson、Sussan Rouhafza、Eric B. Sjogren、David B. Smith、Rebecca A. Stephenson、Francisco X. Talamas、Ann-Marie Waltos、Robert J. Weikert、John C. Wu

  DOI：10.1021/jm9603633

  日期：1996.1.1

  Structure-activity relationships in the region of the phthalide ring of the inosine monophosphate dehydrogenase inhibitor mycophenolic acid have been explored. Replacement of the lactone ring with other cyclic moieties resulted in loss of potency, especially for larger groups. Replacement of the ring by acyclic substituents also indicated a strong sensitivity to steric bulk. A phenolic hydroxyl group, with an adjacent hydrogen bond acceptor, was found to be essential for high potency. The aromatic methyl group was essential for activity; the methoxyl group could be replaced by ethyl to give a compound with 2-4 times the potency of mycophenolic acid in vitro and in vivo.