methyl (E)-6-<(1,3-dihydro-6-methoxy-4-<(methoxyethoxy)methoxy>-7-methyl-3-oxo-5-isobenzofuranyl)methyl>-4-methyl-4-hexenoate | 125198-47-2

• 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: methyl (E)-6-<(1,3-dihydro-6-methoxy-4-<(methoxyethoxy)methoxy>-7-methyl-3-oxo-5-isobenzofuranyl)methyl>-4-methyl-4-hexenoate
• 英文别名: methyl (E)-6-({1,3-dihydro-6-methoxy-4-[(methoxyethoxy)methoxy]-7-methyl-3-oxo-5-isobenzofuranyl}methyl)-4-methyl-4-hexenoate；(E)-6-[1,3-Dihydro-6-methoxy-4-[(2-methoxyethoxy)methoxy]-7-methyl-3-oxo-5-isobenzofuranyl]-4-methyl-4-hexenoic Acid Methyl Ester；methyl (E)-6-[6-methoxy-4-(2-methoxyethoxymethoxy)-7-methyl-3-oxo-1H-2-benzofuran-5-yl]-4-methylhex-4-enoate
• CAS: 125198-47-2
• 化学式: C₂₂H₃₀O₈
• 分子量: 422.475
• InChiKey: MIKOZODALGSQPT-MKMNVTDBSA-N

物化性质

• 熔点：
  119-121 °C(Solv: ethyl ether (60-29-7); hexane (110-54-3))
• 沸点：
  571.4±50.0 °C(Predicted)
• 密度：
  1.169±0.06 g/cm3(Predicted)
• 溶解度：
  扩张型心肌病

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  30
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  89.5
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  methyl (E)-6-<(1,3-dihydro-6-methoxy-4-<(methoxyethoxy)methoxy>-7-methyl-3-oxo-5-isobenzofuranyl)methyl>-4-methyl-4-hexenoate 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 生成 7-O-(2-methoxy-ethoxymethyl)mycophenolic acid
  参考文献：
  名称：

  Synthesis of mycophenolate mofetil-[14C], RS-61443-14C

  摘要：

  描述了一种强效免疫抑制剂氟氟苯酰咪唑（1）的合成，该药物用碳-14标记。通过改进的Hunsdiecker反应，从未标记的氟氟苯酰酸（2）合成了甲氧基乙氧基甲基（MEM）保护的氟氟苯酰氮溴化物（9）。经过三步合成，最终得到的化合物的特定活性为53.8 mCi/mmol，总收率为49.5%，来源于K14CN。

  DOI：

  10.1002/jlcr.2580360508
• 作为产物：
  描述：

  霉酚酸 在 对甲苯磺酸 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 21.0h， 生成 methyl (E)-6-<(1,3-dihydro-6-methoxy-4-<(methoxyethoxy)methoxy>-7-methyl-3-oxo-5-isobenzofuranyl)methyl>-4-methyl-4-hexenoate
  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

• 5-substituted derivatives of mycophenolic acid
  申请人：Syntex (U.S.A.) Inc.

  公开号：US05633279A1

  公开（公告）日：1997-05-27

  The disclosed hexenoic acid side-chain derivatives of mycophenolic acid are therapeutic agents advantageous in the treatment of disease states indicated for mycophenolic acid and/or mycophenolate mofetil, including immune, inflammatory, tumor, proliferative, viral or psoriatic disorders.

  揭示的己烯酸侧链衍生物是治疗免疫、炎症、肿瘤、增殖、病毒或牛皮癣等适用于己烯酸和/或魔麻酯的疾病状态的治疗剂，具有优势。
• Synthesis and immunosuppressive activity of some side-chain variants of mycophenolic acid
  作者：Peter H. Nelson、Elsie Eugui、Ching C. Wang、Anthony C. Allison

  DOI：10.1021/jm00164a057

  日期：1990.2

  The syntheses and immunosuppressive bioassays of 12 side-chain variants of mycophenolic acid are described. The compounds were made either from mycophenolic acid itself or from 5-(chloromethyl)-1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxoisoben zofuran, a versatile intermediate for the synthesis of diverse side-chain variants. Replacement of the methylated E double bond of the natural product with a triple bond, a Z double bond, a saturated bond, or a sulfur atom, with overall chain lengths equal to or greater than that of mycophenolic acid, produced compounds devoid of significant activity. Replacement of the side-chain double bond with difluoro, dibromo, or unsubstituted cyclopropane rings also removed most activity. Replacement of the double bond with an allenic linkage yielded a compound with about one-fifth of the immunosuppressive activity of mycophenolic acid. Some possible causes for the unusual specificity of structure and activity are discussed.
• NELSON, PETER H.;EUGUI, ELSIE;WANG, CHING C.;ALLISON, ANTHONY C., J. MED. CHEM., 33,(1990) N, C. 833-838
  作者：NELSON, PETER H.、EUGUI, ELSIE、WANG, CHING C.、ALLISON, ANTHONY C.

  DOI：——

  日期：——
• 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.
• Synthesis of mycophenolate mofetil-[14C], RS-61443-14C
  作者：Glenn T. Huang、Howard Parnes

  DOI：10.1002/jlcr.2580360508

  日期：1995.5

  Synthesis of the potent immunosuppressive agent, mycophenolate mofetil (1) labelled with carbon-14 is described. Methoxyethoxymethyl (MEM) protected mycophenolate norbromide (9) was prepared from unlabelled mycophenolic acid (2) using a modified Hunsdiecker reaction. A three step synthesis furnished the title compound, having a specific activity of 53.8 mCi/mmol, in 49.5% overall yield from K14CN.

  描述了一种强效免疫抑制剂氟氟苯酰咪唑（1）的合成，该药物用碳-14标记。通过改进的Hunsdiecker反应，从未标记的氟氟苯酰酸（2）合成了甲氧基乙氧基甲基（MEM）保护的氟氟苯酰氮溴化物（9）。经过三步合成，最终得到的化合物的特定活性为53.8 mCi/mmol，总收率为49.5%，来源于K14CN。