摘要
目的研究对甲磺酰基苯丙烯酸的异羟肟酸和酰脲衍生物的合成及其抗炎活性。方法将对甲磺酰基苯丙烯酸转化成其异羟肟酸 (Ⅳ )和酰脲衍生物 (Ⅴ ) ,评价Ⅳ和Ⅴ的抗炎活性以及连续经口服给药对大鼠胃肠道的影响。结果合成了 10个新化合物 (Ⅳ1～Ⅳ5和Ⅴ1～Ⅴ5) ,其结构经IR、1H NMR和MS确证。小鼠试验表明 :Ⅳ1、Ⅳ4、Ⅳ5和Ⅴ1、Ⅴ3 、Ⅴ5的抗炎活性与双氯芬酸钠和罗非昔布相当 (P >0 0 5 ) ;大鼠试验显示 :Ⅴ3 和Ⅴ5的抗炎活性与双氯芬酸钠和罗非昔布相当 (P>0 0 5 ) ,Ⅳ4、Ⅴ3 和Ⅴ5的胃肠道损伤显著小于双氯芬酸钠 (P <0 0 1) ,与罗非昔布和CMC Na相当 (P >0 0 5 )。结论对甲磺酰基苯丙烯酸的异羟肟酸和酰脲衍生物抗炎活性较强 ,胃肠道不良反应小 ,值得深入研究。
Aim To study on synthesis and anti-in flammatory activity of hydroxamic acid and acyl urea derivatives of p-(me thanesulfonyl)phenylpropenoic acids.Method Some of p-(methanesu lfonyl)phenylpropenoic acids were converted to their hydroxamic acids( Ⅳ)and acyl ureas(Ⅴ).The anti-inf lammatory activities against xylene-induced m ic e ear swelling and carrageenan-induced rat paw edema of Ⅳ and Ⅴ were evaluate d,and the side effects of their gastrointestinal tracts(GI) in the rats were exa mined.Results Ten new compounds(Ⅳ 1～Ⅳ 5 and Ⅴ 1～Ⅴ 5)were obtained,and their s tructure s were determined by IR, 1H-NMR and MS.Six of them(Ⅳ 1, Ⅴ 4,Ⅴ 5 and Ⅴ 1,Ⅴ 3,Ⅴ 5)exhibited mark ed anti-inflammatory activity comparable with CMC-Na in xylene-induced m ice ear swelling model,and Ⅴ 3 and Ⅴ 5 showed remarkable anti-inflammatory activity c omparable with diclofenac sodium and selective COX-2 inhibitor rofecoxib in car rag eenan-induced rat paw edema model(P>0 05).Ⅳ 4 a nd Ⅴ 3 and Ⅴ 5 had less GI side effec ts than diclofenac sodium(P<0 01),and no significant difference compared w ith CMC-Na and rofecoxib(P>0 05).Conclusion Hydroxamic acid and acyl urea derivatives of p-(methanesulfonyl)phenylpropenoic acids possess h igh anti-inflammatory activity and less GI side effects than their parent acids .
出处
《中国药物化学杂志》
CAS
CSCD
2004年第5期257-262,M003,共7页
Chinese Journal of Medicinal Chemistry
关键词
药物化学
制备
化学合成
对甲磺酰基苯丙烯酸
羟肟酸
酰脲
抗炎活性
胃肠道副作用
medicinal chemistry
preparation
chemical synthesis
p-(methanesulfonyl)phenylpropenoic acids
hydroxamic acid
acyl urea
anti-in flammatory activity
gastrointestinal side effects
