对氨磺酰基苯亚甲基环酮类化合物的合成及抗炎活性
Synthesis and anti-inflammatory activity of p-(sulfamyl)benzylidene-linked heterocyclic ketone derivatives
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摘要: 目的 ： 研究对氨磺酰基苯亚甲基环酮类化合物的合成及其抗炎活性。 方法 ： 将三环类选择性COX-2抑制剂的药效团对氨磺酰基苯基与五元含氮杂环酮拼合，合成对氨磺酰基苯亚甲基环酮类化合物，采用二甲苯致小鼠耳肿胀及角叉菜胶致大鼠足跖肿胀两种模型评价其抗炎活性，并考察其连续7 d灌胃给药对大鼠胃肠道的影响。 结果 ： 合成了12个目标化合物(LHZ-101～LHZ-112)，结构经质谱、红外光谱、核磁共振氢谱和元素分析确证。小鼠耳肿胀模型显示LHZ-105，LHZ-106，LHZ-111具有明显的抗炎活性；角叉菜胶致大鼠足跖肿胀模型显示LHZ-106，LHZ-111具有较强的抗炎活性；LHZ-105，LHZ-106，LHZ-111的胃肠道副作用小于阳性药双氯芬酸钠和CI-1004。 结论 ： 对氨磺酰基苯亚甲基环酮类化合物具有一定的抗炎活性，胃肠道副作用较小，值得进一步研究。
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关键词:
- COX/5-LOX双重抑制剂 /
- 杂环酮衍生物 /
- 抗炎活性 /
- 胃肠道副作用
Abstract: Aim ：To study the synthesis and anti-inflammatory activity of p-(sulfamyl)benzylidene-linked heterocyclic ketone derivatives. Methods ：A series of p-(sulfamyl)benzylidene-linked heterocyclic ketone derivatives were synthesized.Anti-inflammatory activity was evaluated against xylene-induced ear oedema in mice and against carrageenan-induced paw oedema in rats.Gastrointestinal side effects in the rats were also examined after continuous introgastric administration of these compounds once daily for 7 days. Results ：Twelve compounds(LHZ-101-LHZ-112)were synthesized and their structures were confirmed by IR，1H NMR，MS and elemental analysis.LHZ-105，LHZ-106 and LHZ-111 exhibited marked anti-inflammatory activity in xylene-induced mice ear swelling model.LHZ-106 and LHZ-111 showed significant anti-inflammatory activity in carrageenan-induced rat paw edema model.LHZ-105，LHZ-106 and LHZ-111 had less gastrointestinal side effects than diclofenac sodium and CI-1004. Conclusion ：These results suggest that some of these compounds have the potential for anti-inflammatory activity with few gastrointestinal side effects. -
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