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目的设计合成4H-吡啶并[1,2-a]嘧啶-4-酮取代的双芳基脲类化合物,初步评价其体外抗增殖活性。方法以2-氨基吡啶或2-氨基-4-甲基吡啶为原料,经环合、烃化、还原及酰化共4步反应合成目标化合物;以sorafenib为阳性对照,采用MTT法,测试目标化合物对乳腺癌细胞株MDA-MB-231的抗增殖活性。结果与结论合成了16个未见报道的含4H-吡啶并[1,2-a]嘧啶-4-酮药效团的双芳基脲类化合物,其结构经1H-NMR和MS确证;8个化合物显示较好的体外活性,其中,化合物4h活性突出,为sorafenib的8.3倍。
OBJECTIVE To design and synthesize bis-arylureas substituted with 4H-pyrido [1,2-a] pyrimidin-4-ones and to evaluate their in vitro anti-proliferative activity. Methods The target compounds were synthesized by 4-step reaction of cyclization, alkylation, reduction and acylation with 2-aminopyridine or 2-amino-4-methylpyridine. The target compounds were obtained by sorafenib as positive control and MTT assay Anti-proliferative activity of the compound on breast cancer cell line MDA-MB-231. RESULTS AND CONCLUSION: Sixteen novel bisarylureas containing 4H-pyrido [1,2-a] pyrimidin-4-one pharmacophore were synthesized and their structures were confirmed by 1H-NMR and MS. 8 Compounds showed good in vitro activity, of which compound 4h activity was sorafenib 8.3 times.