新型喹诺酮类化合物的设计合成与生物活性研究

Design,synthesis and biological evaluation of novel quinolones

目的设计合成具有抗肿瘤和抗HIV活性的新型喹诺酮类化合物。方法邻苯二胺衍生物和苯甲酰乙酸乙酯衍生物经缩合关环反应得到目标产物。结果与结论共合成5个未见文献报道的喹诺酮类化合物(7～11),目标化合物的结构经1H-NMR、ESI-MS谱确证。并利用谱学方法解析了此类化合物的互变异构现象。其中,化合物11具有明显的抗肿瘤及抗HIV活性。

As a privileged structure, the quinolone scaffold is well-presented in a variety of therapeutic drugs and bioactive agents. The design and synthesis of novel quinolones as simplified analogues of the anticancer agent flavopiridol were described herein. Five novel quinolone derivatives were prepared via cyclizative con- densation between the aniline derivative 3 and the fl-oxa-ester 6. The structures of the target compounds（7 - 11 ） were confirmed by 1H-NMR and ESI-MS data,and tautomerism of the quinolone scaffold was observed and elucidated with spectral methods. Compound 11 showed an apparent antitumor activity in the SRB assay （GIso = 17.28 -33.72 μmol L-1） and it also exhibited noticeable anti-HIV activities with ECs0 and CC50 values of 21.04 μmol.L-1 and 21.49 μmol.L-1 ,respectively.