2-（E）-（4-甲磺酰基）亚苄基环戊酮Mannich碱类化合物的合成及其抗炎活性研究

【作者】 周乐；

【导师】 董金华；

【作者基本信息】 沈阳药科大学 ， 药物化学， 2004， 硕士

【摘要】 本文介绍了非甾体抗炎药的作用机理及研究进展。设计在具有抗炎作用的取代环戊酮Mannich碱结构中引入抗炎活性基团对甲磺酰苯基，并以对甲磺酰基苯甲醛和环戊酮为原料，合成了13个未见文献报道的新化合物，其中有11个是2-(E)-(4-甲磺酰基)亚苄基环戊酮Mannich碱类衍生物。所有化合物均经核磁共振氢谱和质谱确认。 以二甲苯致小鼠耳肿胀为模型对13个化合物的抗炎活性进行了初步筛选，实验结果显示：在200mg／kg剂量下，化合物2-(E)-(4-甲磺酰基)亚苄基-5-[N-(4-甲氧基)苯基]胺甲基环戊酮(M-3)，2-(E)-(4-甲磺酰基)亚苄基-5-(N-(4-乙氧基)苯基]胺甲基环戊酮(M-4)，2-(E)-(4-甲磺酰基)亚苄基-5-二甲胺甲基环戊酮盐酸盐(M-11)有较强的抗炎活性，其抑制率分别为48.18％，47.45％，50.95％，明显高于10mg／kg剂量的吲哚美辛。更多还原

【Abstract】 In the thesis, the mechanism and the development of the NSAIDs were introduced. We designed a series of compounds, with the ideal : a methanesulfonyl group which was an anti-inflammatory active group was introduced into the Mannich base of substituted cyclopentanone. I started the synthesis work with 4-methanesulfonyl benzaldehyde and cyclopentanone, and got 13 new compounds ,including eleven Mannich bases derivatives of 2-(E)-(4-methanesulfonyl)denzylidene cyclopentanone. All the structures of the compounds were identified by ~1H-NMR and MS.All the compounds were evaluated for anti-inflammatory activity. Preliminary pharmacological tests showed that 2-(E)-(4-methanesulfonyl) benzylidene-5-[N-(4-methoxyl)phenyl]aminomethyl cyclopentanone(M-3), 2-(E)-(4-methanesulfonyl)benzylidene-5-[N-(4-methoxyl)phenyl]aminomethyl cyclopentanone(M-4), and 2-(E)-(4-methanesulfonyl) benzylidene-5-(N-dimethy)aminomethyl cyclopentanone hydrochloride(M-11) exerted good anti-inflammatory activity on xylene-induced ear edema in mice at the dose of 200mg/kg, superior to that of Indomethacin at the dose of 10mg/kg. The inhabitation rate of the 3 compounds was showed in the range of 47-50%.更多还原