N-mycophenoyl-L-valine

• 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: N-mycophenoyl-L-valine
• 英文别名: mycophenolic-L-valine；(2S)-2-[[(E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1H-2-benzofuran-5-yl)-4-methylhex-4-enoyl]amino]-3-methylbutanoic acid
• 化学式: C₂₂H₂₉NO₇
• 分子量: 419.475
• InChiKey: KGOFUHNHMOROMR-VQANOXKBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  122
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-mycophenoyl-L-valine 、 5'-amino-5'-deoxyadenosine hydrochloride 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以42%的产率得到(E)-N-[(2S)-1-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methylamino]-3-methyl-1-oxobutan-2-yl]-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1H-2-benzofuran-5-yl)-4-methylhex-4-enamide
  参考文献：
  名称：

  NAD-based inhibitors with anticancer potential

  摘要：

  Three classes of novel inhibitors of inosine monophosphate dehydrogenase have been prepared and their anti-proliferative properties were evaluated against several cancer cell lines.(1) Mycophenolic adenine dinucleotide analogues (8-13) containing a substituent at the C2 of adenine ring were found to be potent inhibitors of IMPDH (K-i's in range of 0.6-82 nM) and sub-mu M inhibitors of leukemic K562 cell proliferation. (2) Mycophenolic adenosine (D and L) esters (20 and 21) showed a potent inhibition of IMPDH2 (K-i = 102 and K-i = 231 nM, respectively) and inhibition of K562 cell growth (IC50 = 0.5 and IC50 = 1.6 mu M). These compounds serve both as inhibitors of the enzyme and as a depot form of mycophenolic acid. The corresponding amide analogue 22, also a potent inhibitor of IMPDH (K-i = 84 nM), did not inhibit cancer cell proliferation. (3) Mycophenolic-(L)-and (D)-valine adenine diamide derivatives 25 (K-i = 9 nM) and 28 (K-i = 3 nM) were found to be very potent enzymatically, but did not inhibit proliferation of cancer cells. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.11.005
• 作为产物：
  描述：

  霉酚酸 在 甲醇 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium hydroxide 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 生成 N-mycophenoyl-L-valine
  参考文献：
  名称：

  NAD-based inhibitors with anticancer potential

  摘要：

  Three classes of novel inhibitors of inosine monophosphate dehydrogenase have been prepared and their anti-proliferative properties were evaluated against several cancer cell lines.(1) Mycophenolic adenine dinucleotide analogues (8-13) containing a substituent at the C2 of adenine ring were found to be potent inhibitors of IMPDH (K-i's in range of 0.6-82 nM) and sub-mu M inhibitors of leukemic K562 cell proliferation. (2) Mycophenolic adenosine (D and L) esters (20 and 21) showed a potent inhibition of IMPDH2 (K-i = 102 and K-i = 231 nM, respectively) and inhibition of K562 cell growth (IC50 = 0.5 and IC50 = 1.6 mu M). These compounds serve both as inhibitors of the enzyme and as a depot form of mycophenolic acid. The corresponding amide analogue 22, also a potent inhibitor of IMPDH (K-i = 84 nM), did not inhibit cancer cell proliferation. (3) Mycophenolic-(L)-and (D)-valine adenine diamide derivatives 25 (K-i = 9 nM) and 28 (K-i = 3 nM) were found to be very potent enzymatically, but did not inhibit proliferation of cancer cells. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.11.005

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.
• NAD-based inhibitors with anticancer potential
  作者：Krzysztof Felczak、Robert Vince、Krzysztof W. Pankiewicz

  DOI：10.1016/j.bmcl.2013.11.005

  日期：2014.1

  Three classes of novel inhibitors of inosine monophosphate dehydrogenase have been prepared and their anti-proliferative properties were evaluated against several cancer cell lines.(1) Mycophenolic adenine dinucleotide analogues (8-13) containing a substituent at the C2 of adenine ring were found to be potent inhibitors of IMPDH (K-i's in range of 0.6-82 nM) and sub-mu M inhibitors of leukemic K562 cell proliferation. (2) Mycophenolic adenosine (D and L) esters (20 and 21) showed a potent inhibition of IMPDH2 (K-i = 102 and K-i = 231 nM, respectively) and inhibition of K562 cell growth (IC50 = 0.5 and IC50 = 1.6 mu M). These compounds serve both as inhibitors of the enzyme and as a depot form of mycophenolic acid. The corresponding amide analogue 22, also a potent inhibitor of IMPDH (K-i = 84 nM), did not inhibit cancer cell proliferation. (3) Mycophenolic-(L)-and (D)-valine adenine diamide derivatives 25 (K-i = 9 nM) and 28 (K-i = 3 nM) were found to be very potent enzymatically, but did not inhibit proliferation of cancer cells. (C) 2013 Elsevier Ltd. All rights reserved.