7-O-(2-methoxy-ethoxymethyl)mycophenolic acid | 165684-38-8

• 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-O-(2-methoxy-ethoxymethyl)mycophenolic acid
• 英文别名: mycophenolic acid MEM ether；(E)-6-(1,3-dihydro-6-methoxy-4-methoxyethoxymethoxy-7-methyl-3-oxoisobenzofuran-5-yl)-4-methyl-4-hexenoic acid；(E)-6-[6-methoxy-4-(2-methoxyethoxymethoxy)-7-methyl-3-oxo-1H-2-benzofuran-5-yl]-4-methylhex-4-enoic acid
• CAS: 165684-38-8
• 化学式: C₂₁H₂₈O₈
• 分子量: 408.449
• InChiKey: WHAPJVJBKZSZAF-WLRTZDKTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  29
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  7-O-(2-methoxy-ethoxymethyl)mycophenolic acid 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 乙酸乙酯 为溶剂， 反应 1.0h， 生成
  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：

  霉酚酸 在 氢氧化钾 、 对甲苯磺酸 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 69.0h， 生成 7-O-(2-methoxy-ethoxymethyl)mycophenolic 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

文献信息

• 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。
• 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。
• Mycophenolate dianions
  作者：John C. Rohloff、John O. Gardner、R.W. Towne

  DOI：10.1016/0040-4039(95)01652-x

  日期：1995.10

  Dianions derived from simple protected derivatives of mycophenolic acid were utilized to synthesize the highly potent semisynthetic analogue (S)-alpha-methylmycophenolic acid and the natural product 3-hydroxymycophenolic acid.
• 5-SUBSTITUTED DERIVATIVES OF MYCOPHENOLIC ACID
  申请人：SYNTEX (U.S.A.) INC.

  公开号：EP0745073B1

  公开（公告）日：2000-07-12
• US5493030A
  申请人：——

  公开号：US5493030A

  公开（公告）日：1996-02-20