Idelalisib类似物的合成及其抗肿瘤活性研究

Synthesis and Antitumor Activity Evaluation of Idelalisib Analogs

为了寻找高效的潜在抗肿瘤药物,设计合成Idelalisib类似物并测定其抗肿瘤活性。以2-氟-6-硝基苯甲酸为起始原料,经缩合、还原、脱保护和胺化反应等5步反应合成目标化合物,并采用MTT法对所合成的化合物进行抗肿瘤活性的测定。所有的目标化合物结构均经氢谱和高分辨质谱进行确证。其中,(S)-2-(2-((9H-嘌呤-6-基)氨基)-3-苯基丙酰胺基)-6-氟-N-苯基苯甲酰胺的抗肿瘤活性最强,它对4种肿瘤细胞的抗肿瘤活性均优于阳性对照药物Idelalisib,具有后续研究的价值。

Idelalisib analogs were designed and synthesized and their antitumor activity was determined in order to find potential antitumor drugs with high efficacy.The target compounds were synthesized from 2-fluoro-6-nitrobencoic acid through five steps of condenstation,reduction,deprotection and amination,and the antitumor activity of the compounds was determined by MTT assay.All structures of the target compounds were confirmed by 1HNMR and HRMS.Among them,the compound(S)-2-(2-((9H-purin-6-yl)amino)-3-phenylpropanmido)6-fluoro-N-phenylbenzamide showed the most anti-tumor activity,and its anti-tumor activity on 4 tumor cell lines(Raji,SU-DHL-10,HepG-2 and A549)was better than that of the positive control drug Idelalisib,which has good follow-up research value in the future.