新结构嘧啶类化合物的合成及抗肿瘤活性筛选  

Synthesis and antitumor activities of pyrimidines

作　　者：游文玮[1] 赵培亮[1] 邹敏[1] 周中振[1] 段安娜[1] 吴曙光[1] 

机构地区：[1]南方医科大学药学院,广东广州510515

出　　处：《南方医科大学学报》2011年第5期875-877,共3页Journal of Southern Medical University

基　　金：教育部博士点新教师基金(20104433120011);广东省自然科学基金(10451051501004725);广东省医学科研基金(B2010185)

摘　　要：目的合成具有抗肿瘤活性的新型CDKs抑制剂,并评价其抗肿瘤活性。方法根据生物活性叠加原理,将1(-甲磺酰基)哌啶-4-氨和嘧啶杂环片段合理组合,设计合成了5个结构新颖的N4-取代苯胺基-N2-(1-甲磺酰基哌啶-4-氨基)-5-硝基嘧啶类化合物3a^3e。结果目标化合物的结构经质谱和核磁共振氢谱等表征确认。采用MTT法测试了目标化合物抑制肿瘤细胞增殖活性。测试结果表明,部分化合物对MCF-7(人乳腺癌细胞)肿瘤细胞有弱的细胞毒性,而对HepG2(人肝癌细胞)没有抑制活性,表现出一定的选择性。结论化合物3b对MCF-7(人乳腺癌细胞)肿瘤细胞有较强的抑制活性(IC50=13.6μmo·lL-1)。初步的构效关系研究表明化合物的立体结构可能对其抗肿瘤活性影响较大。Objective To synthesize cyclin-dependent kinase（CDKs） inhibitors and assay their antitumor activities. Methods A series of pyrimidines containing different arylamino and 1-（methylsulfonyl） piperidin moieties were designed by combining the segments 1-（methylsulfonyl） piperidin and pyrimidine heterocycles according to the super-postion principle of the reinforcement of biological activities. Results Their structures were characterized by MS and 1H NMR spectra and all the synthesized compounds were screened for their antimicrobial activity with MTT assay. Conclusion The preliminary bioassay showed that compound 3b displayed good antitumor activity（IC50=13.6 μmol/L） . The preliminary structure activity relationship analysis of these analogues suggest that the steric factor may have important impact on the anti-tumor activity.

关 键 词：嘧啶 合成 抗肿瘤活性 

分 类 号：R914.5[医药卫生—药物化学]