dimethyl 2-[(2E)-but-2-en-1-ylidene]succinate | 34817-27-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: dimethyl 2-[(2E)-but-2-en-1-ylidene]succinate
• 英文别名: Methyl-3-carbomethoxy-3,5-heptadienoat
• CAS: 34817-27-1；58838-15-6；58838-16-7
• 化学式: C₁₀H₁₄O₄
• 分子量: 198.219
• InChiKey: YECCBHYQDHAAPS-FKQQABSFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.23
• 重原子数：
  14.0
• 可旋转键数：
  4.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  52.6
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  dimethyl 2-[(2E)-but-2-en-1-ylidene]succinate 在 sodium hydroxide 作用下， 以 水 为溶剂， 反应 96.0h， 以56%的产率得到2-[(2E)-but-2-en-1-ylidene]succinic acid
  参考文献：
  名称：

  Simultaneous presence of unsaturation and long alkyl chain at P1′ of Ilomastat confers selectivity for gelatinase A (MMP-2) over gelatinase B (MMP-9) inhibition as shown by molecular modelling studies

  摘要：

  Structural analogues of Ilomastat (Galardin (R)), containing unsaturation(s) and chain extension carrying bulky phenyl group or alkyl moieties at P-1(') were synthesized and purified by centrifugal partition chromatography. They were analyzed for their inhibitory capacity towards MMP-1, MMP-2, MMP-3, MMP-9 and MMP-14, main endopeptidases involved in tumour progression. Presence of unsaturation(s) decreased the inhibitory potency of compounds but, in turn increased their selectivity for gelatinases. 2b and 2d derivatives with a phenyl group inhibited preferentially MMP-9 with IC50 equal to 45 and 38 nM, respectively, but also display activity against MMP-2 IC50 equal to 280 and 120 nM, respectively). Molecular docking computations confirmed affinity of these substances for both gelatinases. With aims to obtain a specific gelatinase A (MMP-2) inhibitor, P, of Ilomastat was modified to carry one unsaturation coupled to an alkyl chain with pentylidene group. Docking studies indicated that MMP-2, but not MMP-9, could accommodate such substitution; indeed 2a proved to inhibit MMP-2 (IC50 = 123 nM), while displaying no inhibitory capacity towards MMP-9. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.05.001
• 作为产物：
  描述：

  马来酸二甲酯 、 丁烯-2-醛 在 三丁基膦 作用下， 以 四氢呋喃 为溶剂， 反应 96.0h， 以85%的产率得到dimethyl 2-[(2E)-but-2-en-1-ylidene]succinate
  参考文献：
  名称：

  Simultaneous presence of unsaturation and long alkyl chain at P1′ of Ilomastat confers selectivity for gelatinase A (MMP-2) over gelatinase B (MMP-9) inhibition as shown by molecular modelling studies

  摘要：

  Structural analogues of Ilomastat (Galardin (R)), containing unsaturation(s) and chain extension carrying bulky phenyl group or alkyl moieties at P-1(') were synthesized and purified by centrifugal partition chromatography. They were analyzed for their inhibitory capacity towards MMP-1, MMP-2, MMP-3, MMP-9 and MMP-14, main endopeptidases involved in tumour progression. Presence of unsaturation(s) decreased the inhibitory potency of compounds but, in turn increased their selectivity for gelatinases. 2b and 2d derivatives with a phenyl group inhibited preferentially MMP-9 with IC50 equal to 45 and 38 nM, respectively, but also display activity against MMP-2 IC50 equal to 280 and 120 nM, respectively). Molecular docking computations confirmed affinity of these substances for both gelatinases. With aims to obtain a specific gelatinase A (MMP-2) inhibitor, P, of Ilomastat was modified to carry one unsaturation coupled to an alkyl chain with pentylidene group. Docking studies indicated that MMP-2, but not MMP-9, could accommodate such substitution; indeed 2a proved to inhibit MMP-2 (IC50 = 123 nM), while displaying no inhibitory capacity towards MMP-9. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.05.001