5-(3,4-dimethoxycinnamoylamido)-3-oxapentyl 3-(trioxsalen-4'-yl)acrylate | 1261297-74-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 5-(3,4-dimethoxycinnamoylamido)-3-oxapentyl 3-(trioxsalen-4'-yl)acrylate
• 英文别名: 2-[2-[[(E)-3-(3,4-dimethoxyphenyl)prop-2-enoyl]amino]ethoxy]ethyl (E)-3-(2,5,9-trimethyl-7-oxofuro[3,2-g]chromen-3-yl)prop-2-enoate
• CAS: 1261297-74-8
• 化学式: C₃₂H₃₃NO₉
• 分子量: 575.615
• InChiKey: ITOXWFKCFINPJM-AMMQDNIMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  42
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  123
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (E)-3-(trioxsalen-4'-yl)propenoic acid 、 (E)-N-(5-hydroxy-3-oxapentyl)-3,4-dimethoxycinnamamide 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 0.75h， 以68%的产率得到5-(3,4-dimethoxycinnamoylamido)-3-oxapentyl 3-(trioxsalen-4'-yl)acrylate
  参考文献：
  名称：

  Does conjugation of antioxidants improve their antioxidative/anti-inflammatory potential?

  摘要：

  A series of symmetric and asymmetric spermine (SPM) conjugates with all-trans-retinoic acid (ATRA), acitretin (ACI), (E)-3-(trioxsalen-4'-yl)acrylic acid (TRAA) and L-DOPA, amides of ACI, L-DOPA and TRAA with 1-aminobutane, benzylamine, dopamine and 1,12-diaminobutane as well as hybrid conjugates of O,O'-dimethylcaffeic acid (DMCA) with TRAA or N-fumaroyl-indole-3-carboxanilide (FICA) and 2-(2-aminoethoxy) ethanol were synthesized and their antioxidant properties were studied. The reducing activity (RA)% of the compounds were evaluated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical-scavenging assay and found to be in the range 0-92(20 min)%/96(60 min)% at 100 mu M, the most powerful being the conjugates L-DOPA-SPM-L-DOPA (8, RA = 89%/96%) and L-DOPA-dopamine (13, RA = 92%/92%). Conjugate DMCA-NH(CH2CH2O)(2)-FICA (14) was the most powerful LOX inhibitor with IC50 33.5 mu M, followed by the conjugates ACI-NHCH2Ph (10, IC50 40.5 mu M), ACI-SPM-TRAA (7, IC50 41.5 mu M), DMCA-NH(CH2CH2O)(2)-TRAA (15, IC50 65 mu M), 13 (IC50 81.5 mu M) and ACI-dopamine (11, IC50 87 mu M). The most potent inhibitors of lipid peroxidation at 100 mu M were the conjugates 15 (98%) and ACI-SPM-ACI (4, 97%) whereas all other compounds showed activities comparable or lower than trolox. The most interesting compounds, namely ATRA-SPM-ATRA (3), 4, 10, 11 and 15, as well as unconjugated compounds such as ATRA and dopamine, were studied for their anti-inflammatory activity in vivo on rat paw oedema induced by Carrageenan and found to exhibit, for doses of 0.01 mmol/mL of conjugates per Kg of rat body weight, weaker anti-inflammatory activities (3.6-40%) than indomethacin (47%) with conjugate 3 being the most potent (40%) in this series of compounds. The cytocompatibility of selected compounds was evaluated by the viability of RAMEC cells in the presence of different concentrations (0.5-50 mu M) of the compounds. Conjugates 3 (IC50 2.6 mu M) and 4 (IC50 4.7 mu M) were more cytotoxic than the corresponding unconjugated retinoids ATRA (IC50 18.3 mu M) and ACI (IC50 14.6 mu M), whereas conjugate 15 (IC50 12.9 mu M) was less cytotoxic than either DCSP (IC50 11.3 mu M) or the tert-butyl ester of TRAA (IC50 2.9 mu M). (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.10.012

文献信息

• Does conjugation of antioxidants improve their antioxidative/anti-inflammatory potential?
  作者：Dimitra Hadjipavlou-Litina、George E. Magoulas、Stavros E. Bariamis、Denis Drainas、Konstantinos Avgoustakis、Dionissios Papaioannou

  DOI：10.1016/j.bmc.2010.10.012

  日期：2010.12

  A series of symmetric and asymmetric spermine (SPM) conjugates with all-trans-retinoic acid (ATRA), acitretin (ACI), (E)-3-(trioxsalen-4'-yl)acrylic acid (TRAA) and L-DOPA, amides of ACI, L-DOPA and TRAA with 1-aminobutane, benzylamine, dopamine and 1,12-diaminobutane as well as hybrid conjugates of O,O'-dimethylcaffeic acid (DMCA) with TRAA or N-fumaroyl-indole-3-carboxanilide (FICA) and 2-(2-aminoethoxy) ethanol were synthesized and their antioxidant properties were studied. The reducing activity (RA)% of the compounds were evaluated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical-scavenging assay and found to be in the range 0-92(20 min)%/96(60 min)% at 100 mu M, the most powerful being the conjugates L-DOPA-SPM-L-DOPA (8, RA = 89%/96%) and L-DOPA-dopamine (13, RA = 92%/92%). Conjugate DMCA-NH(CH2CH2O)(2)-FICA (14) was the most powerful LOX inhibitor with IC50 33.5 mu M, followed by the conjugates ACI-NHCH2Ph (10, IC50 40.5 mu M), ACI-SPM-TRAA (7, IC50 41.5 mu M), DMCA-NH(CH2CH2O)(2)-TRAA (15, IC50 65 mu M), 13 (IC50 81.5 mu M) and ACI-dopamine (11, IC50 87 mu M). The most potent inhibitors of lipid peroxidation at 100 mu M were the conjugates 15 (98%) and ACI-SPM-ACI (4, 97%) whereas all other compounds showed activities comparable or lower than trolox. The most interesting compounds, namely ATRA-SPM-ATRA (3), 4, 10, 11 and 15, as well as unconjugated compounds such as ATRA and dopamine, were studied for their anti-inflammatory activity in vivo on rat paw oedema induced by Carrageenan and found to exhibit, for doses of 0.01 mmol/mL of conjugates per Kg of rat body weight, weaker anti-inflammatory activities (3.6-40%) than indomethacin (47%) with conjugate 3 being the most potent (40%) in this series of compounds. The cytocompatibility of selected compounds was evaluated by the viability of RAMEC cells in the presence of different concentrations (0.5-50 mu M) of the compounds. Conjugates 3 (IC50 2.6 mu M) and 4 (IC50 4.7 mu M) were more cytotoxic than the corresponding unconjugated retinoids ATRA (IC50 18.3 mu M) and ACI (IC50 14.6 mu M), whereas conjugate 15 (IC50 12.9 mu M) was less cytotoxic than either DCSP (IC50 11.3 mu M) or the tert-butyl ester of TRAA (IC50 2.9 mu M). (C) 2010 Elsevier Ltd. All rights reserved.