二氢吡咯并吡嗪酮衍生物的合成和抗炎镇痛作用

Synthesis and anti-inflammatory and analgesic activities of dihydropyrrolo[1,2-a]pyrazin-1-one

目的研究 3,4 二氢吡咯并 [1,2 a]吡嗪 1 酮 (Ⅱ )类化合物的抗炎镇痛作用构效关系。方法通过 2 吡咯甲酸甲酯与N 氯乙腈的烃基化反应 ,制得N 氰甲基吡咯 2 甲酸甲酯 (Ⅳ ) ,Ⅳ经还原、环合、Friedel Crafts酰基化反应 ,生成 6 芳酰基 2 甲基 3,4 二氢吡咯并 [1,2 a]吡嗪 1 酮类化合物 ;用小鼠测试了所合成化合物的抗炎镇痛活性。结果与结论合成了 13个目标化合物 ;小鼠试验表明 ,一些所合成的化合物具有明显的抗炎和 /或镇痛作用 ,其中 ,ZP16

Aim To study the structure activity relationship(SAR) of the title compounds and search for new anti inflammatory and analgesic agents.Methods 6 Aroyl 2 methyl 3,4 dihydropyrrolopyrazin 1 ones were designed based on the known SAR.The 3,4 dihydropyrrolopyrazin 1 one moiety(Ⅱ)was prepared from methyl 2 pyrrolecarboxylate by N alkylation,reduction and cyclization The Friedel Crafts reaction of Ⅱ with acyl chloride afforded the 6 aroyl derivatives The anti inflammatory and analgesic activities were tested in mice.Results and Conclusion Thirteen of 6 aroyl 2 methyl 3,4 dihydropyrrolopyrazin 1 ones were synthesized.Most of the compounds showed remarkable anti inflammatory and/or analgesic activities in mice The activities of compound ZP163 are equal to those of ibuprofen.