摘要
为了寻找高效低毒的非甾体抗炎药物,将5-氯-2-吲哚酮与氯甲酸苯酯经酯化及水解制得1-苯氧羰基-5-氯-2-吲哚酮,在4-N,N-二甲氨基吡啶作用下与对甲磺酰基苯甲酰氯反应,经酸化得1-苯氧羰基-3-[羟基-(p-甲磺酰基)苯甲撑基]-5-氯-2-吲哚酮(II1),最后与相应的胺(氨)反应,经盐酸中和制得未见文献报道的目标化合物II2~II15,其结构经IR,1HNMR,MS和元素分析确证.二甲苯致小鼠耳肿胀模型测试显示II10,II11,II15具有明显的抗炎活性;角叉菜胶致大鼠足跖肿胀模型试验结果表明,II10,II11抗炎活性与双氯芬酸钠和替尼达普钠相当(P>0.05);其中II11的胃肠道副作用显著小于双氯芬酸钠(P<0.05)和替尼达普钠(P<0.01).
In order to search for new compounds with stronger anti-inflammatory activity and less side effects, phenyl 5-chloro-2-oxindole-1-carboxylate, obtained from 5-chloro-2-oxindole via esterification with phenyl chloroformate and subsequent hydrolyzation, reacted with 4-(methylsulfonyl) benzoyl chloride and 4-dimethylaminopyridine, followed by acidification with hydrochloric acid to yield phenyl 5-chloro- 3-(hydroxy-p-methylsulfonylphenylmethylene)-2-oxo-2,3-dihydroindole-1-carboxylate (Ⅱ1), which was condensed with corresponding amines, followed by acidification with hydrochloride acid to afford the target compounds Ⅱ2-Ⅱ15, respectively. Fifteen novel title compounds were synthesized, and their structures were confirmed by IR, ^1H NMR, MS spectra and elemental analyses. Ⅱ10, Ⅱ11 and Ⅱ15 exhibited marked anti-inflammatory activity in xylene-induced mice ear swelling model. Moreover, Ⅱ10 and Ⅱ11 showed significant anti-inflammatory activity comparable to diclofenac sodium and tenidap sodium (P〉0.05) in carrageenan-induced rat paw edema model. Ⅱ11 had less gastrointestinal side effect than diclofenac sodium (P〈0.05) and tenidap sodium (P〈0.01).
出处
《有机化学》
SCIE
CAS
CSCD
北大核心
2007年第6期733-738,共6页
Chinese Journal of Organic Chemistry
基金
中国药科大学"211"工程人才引进基金(No.211020)资助项目.