7-hydroxy-5-methoxy-4-methyl-6-[(E)-3-methyl-6-[(2R)-oxiran-2-yl]-6-oxohex-2-enyl]-3H-2-benzofuran-1-one | 1451181-36-4

• 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: 7-hydroxy-5-methoxy-4-methyl-6-[(E)-3-methyl-6-[(2R)-oxiran-2-yl]-6-oxohex-2-enyl]-3H-2-benzofuran-1-one
• CAS: 1451181-36-4
• 化学式: C₁₉H₂₂O₆
• 分子量: 346.38
• InChiKey: YFLWZQMXZAUGIL-GSDOMDMQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  85.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  霉酚酸 在 titanium(IV) isopropylate 、 叔丁基过氧化氢 、 L-(+)-酒石酸二异丙酯 、 四丁基氟化铵 、 水 、 二异丁基氢化铝 、 戴斯-马丁氧化剂 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 生成 7-hydroxy-5-methoxy-4-methyl-6-[(E)-3-methyl-6-[(2R)-oxiran-2-yl]-6-oxohex-2-enyl]-3H-2-benzofuran-1-one
  参考文献：
  名称：

  Discovery of N-(2,3,5-triazoyl)mycophenolic amide and mycophenolic epoxyketone as novel inhibitors of human IMPDH

  摘要：

  Syntheses of ten derivatives of mycophenolic acid (MPA) at C-6' position, and structure-activity relationship study among these derivatives, MPA and mycophenolic hydroxamic acid (MPHA) led to discovery of N-(2,3,5-triazolyl)mycophenolic amide 4, (7'S) mycophenolic epoxyketone 9 and (7'R) mycophenolic epoxyketone 10 having potent inhibitory activity against human inosine-5'-monophosphate dehydrogenase (IMPDH) type land II as well as antiproliferative activity on human leukemia K562 cells. Compounds 4, 9, and 10 showed induction activity of erythroid differentiation in K562 cells. Inhibitory effects of 4 and 10 against IMPDH were attenuated by supplemental guanosine in K562 cells. In contrast, attenuation effect by supplemental guanosine was not significant in the case of 9. Compound 9 weakly inhibited the enzyme activity of HDAC in the nuclear lysate of K562 cells at 10 mu M. These observations suggest that the primary target of 4, 9, and 10 is IMPDH, whereas compound 9 partially inhibits a certain type of HDAC. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.07.016

文献信息

• Discovery of N-(2,3,5-triazoyl)mycophenolic amide and mycophenolic epoxyketone as novel inhibitors of human IMPDH
  作者：Kazuhiro Sunohara、Shinya Mitsuhashi、Kengo Shigetomi、Makoto Ubukata

  DOI：10.1016/j.bmcl.2013.07.016

  日期：2013.9

  Syntheses of ten derivatives of mycophenolic acid (MPA) at C-6' position, and structure-activity relationship study among these derivatives, MPA and mycophenolic hydroxamic acid (MPHA) led to discovery of N-(2,3,5-triazolyl)mycophenolic amide 4, (7'S) mycophenolic epoxyketone 9 and (7'R) mycophenolic epoxyketone 10 having potent inhibitory activity against human inosine-5'-monophosphate dehydrogenase (IMPDH) type land II as well as antiproliferative activity on human leukemia K562 cells. Compounds 4, 9, and 10 showed induction activity of erythroid differentiation in K562 cells. Inhibitory effects of 4 and 10 against IMPDH were attenuated by supplemental guanosine in K562 cells. In contrast, attenuation effect by supplemental guanosine was not significant in the case of 9. Compound 9 weakly inhibited the enzyme activity of HDAC in the nuclear lysate of K562 cells at 10 mu M. These observations suggest that the primary target of 4, 9, and 10 is IMPDH, whereas compound 9 partially inhibits a certain type of HDAC. (C) 2013 Elsevier Ltd. All rights reserved.