methyl ester N-mycophenoyl-L-phenylalanine

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl ester N-mycophenoyl-L-phenylalanine
• 英文别名: methyl (E)-(6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4-enoyl)phenylalaninate；methyl (2S)-2-[[(E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1H-2-benzofuran-5-yl)-4-methylhex-4-enoyl]amino]-3-phenylpropanoate
• 化学式: C₂₇H₃₁NO₇
• 分子量: 481.546
• InChiKey: XOGCDZNQHQHLMG-DCINASHKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  35
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl ester N-mycophenoyl-L-phenylalanine 在 lithium hydroxide monohydrate 作用下， 以 甲醇 、 水 为溶剂， 反应 48.0h， 以59%的产率得到N-mycophenoyl-L-phenylalanine
  参考文献：
  名称：

  Synthesis and biological activity of mycophenolic acid-amino acid derivatives

  摘要：

  In search of new immunosuppressants we synthesized 11 amino acids derivatives of MPA as methyl esters 10a-k using EDCl/DMAP and their corresponding amino acid derivatives in free acid form ha k by hydrolysis of ester group with LiOH/MeOH. New analogs were evaluated as growth inhibitors of lymphoid cell line (Jurkat) and human peripheral blood mononuclear cells (PBMC) from healthy donors. According to obtained results recovering of free carboxylic group increased their activity. Additionally, the cytotoxic properties depends on the substituent and configuration at chiral center in amino acid unit. The compounds 10j, lie and 11h exhibited higher potency than MPA 1 in vitro. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.09.026
• 作为产物：
  描述：

  L-苯丙氨酸甲酯 、 霉酚酸 在 联苯-4-酰胺肟 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以67%的产率得到methyl ester N-mycophenoyl-L-phenylalanine
  参考文献：
  名称：

  霉酚酸衍生物作为潜在抗弓形虫剂的合成和评价

  摘要：

  设计合成了19种霉酚酸（MPA）衍生物，并首次评估了它们的抗弓形虫活性。其中，N-丙基咪唑修饰的化合物E5表现出最强的活性，对弓形虫感染后HFF-1（人类包皮成纤维细胞-1）细胞的IC 50为80.9 μM（MPA-211.5 μM）及其选择性指数是 2.2 (MPA-1.2)。体内实验，E5可显着抑制弓形虫急性感染小鼠腹腔内速殖子的增殖(抑制率46.7%)，且这种抑制作用大于螺旋霉素(抑制率31.3%)和MPA(抑制率15.9%)，说明E5在弓形虫急性感染期间对宿主具有显着的保护作用。此外，E5可降低受感染小鼠血清中丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）水平，显着升高肝脏中谷胱甘肽（GSH）水平，显着降低丙二醛（MDA）水平，表明它对弓形虫感染具有保肝作用。同样，E5可以缓解急性弓形虫引起的肝脾肿大感染。螺旋霉素会加重受感染小鼠的食欲减退，而E5 则不会。总之，结果表明E5具有作为候选抗弓形虫药物的潜力。

  DOI：

  10.1007/s00044-021-02803-9

文献信息

• Synthesis and biological activity of mycophenolic acid-amino acid derivatives
  作者：Dorota Iwaszkiewicz-Grzes、Grzegorz Cholewinski、Agata Kot-Wasik、Piotr Trzonkowski、Krystyna Dzierzbicka

  DOI：10.1016/j.ejmech.2013.09.026

  日期：2013.11

  In search of new immunosuppressants we synthesized 11 amino acids derivatives of MPA as methyl esters 10a-k using EDCl/DMAP and their corresponding amino acid derivatives in free acid form ha k by hydrolysis of ester group with LiOH/MeOH. New analogs were evaluated as growth inhibitors of lymphoid cell line (Jurkat) and human peripheral blood mononuclear cells (PBMC) from healthy donors. According to obtained results recovering of free carboxylic group increased their activity. Additionally, the cytotoxic properties depends on the substituent and configuration at chiral center in amino acid unit. The compounds 10j, lie and 11h exhibited higher potency than MPA 1 in vitro. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Synthesis and evaluation of mycophenolic acid derivatives as potential anti-Toxoplasma gondii agents
  作者：Fan-Fan Shang、Mei-Yuan Wang、Jiang-Ping Ai、Qing-Kun Shen、Hong-Yan Guo、Chun-Mei Jin、Fen-Er Chen、Zhe-Shan Quan、Lili Jin、Changhao Zhang

  DOI：10.1007/s00044-021-02803-9

  日期：2021.12

  Nineteen mycophenolic acid (MPA) derivatives were designed and synthesized, and their anti-Toxoplasma activity evaluated for the first time. Among them, N-propylimidazole-modified compound E5 demonstrated the strongest activity, and the IC50 against HFF-1 (Human Foreskin Fibroblasts-1) cells following infection with T. gondii is 80.9 μM (MPA-211.5 μM) and its selectivity index is 2.2 (MPA-1.2). In

  设计合成了19种霉酚酸（MPA）衍生物，并首次评估了它们的抗弓形虫活性。其中，N-丙基咪唑修饰的化合物E5表现出最强的活性，对弓形虫感染后HFF-1（人类包皮成纤维细胞-1）细胞的IC 50为80.9 μM（MPA-211.5 μM）及其选择性指数是 2.2 (MPA-1.2)。体内实验，E5可显着抑制弓形虫急性感染小鼠腹腔内速殖子的增殖(抑制率46.7%)，且这种抑制作用大于螺旋霉素(抑制率31.3%)和MPA(抑制率15.9%)，说明E5在弓形虫急性感染期间对宿主具有显着的保护作用。此外，E5可降低受感染小鼠血清中丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）水平，显着升高肝脏中谷胱甘肽（GSH）水平，显着降低丙二醛（MDA）水平，表明它对弓形虫感染具有保肝作用。同样，E5可以缓解急性弓形虫引起的肝脾肿大感染。螺旋霉素会加重受感染小鼠的食欲减退，而E5 则不会。总之，结果表明E5具有作为候选抗弓形虫药物的潜力。