Synthesis And Biological Evaluation Of Novel Steroidal Triazolopyrimidines

Steroids bearing heterocycles fused to the A-or D-ring have been of interest as many of them possess potent bioactivities. In addition,1,2,4-triazolo[1,5-a]pyrimidines derivatives exhibited multifaceted bioactivities and have been widely investigated. In this thesis, two series of16-arylidenosteroids were prepared via the reaction of readily available4-aza-androst-3,17-dione and DHEA with aromatic aldehydes. Subsequently, the intermediates reacted with3-amino-1,2,4-triazole to afford the corresponding novel steroidal triazolopyrimidines. Our work was carried out as follows.1. The Claisen-Schmidt condensation reaction of ketosteroids with aromatic aldehydes catalyzed by the high-efficiency catalyst KF/AI2O3was first reported, which provided a facile approach for the synthesis of arylidenosteroids derivatives.2. Two series of16-arylidenosteroids3a-3o,4a-4k were prepared from the starting substrates4-aza-androst-3,17-dione (la) and DHEA (1b), most of which exhibited a certain antitumor activity to PC-3and EC109cells in vitro and compound4c showed potent inhibitory activity against EC109cells.3. The preparation of novel steroidal[17,16-d][1,2,4]triazolo[1,5-a]pyrimidines5a-5o and6a-6k was first reported. All the synthesized new steroidal heterocycles were characterized by1H, C NMR and mass spectra, and the structure of5b was further established by X-ray analysis.4. All the synthesized compounds were evaluated for their anticancer activity in vitro against PC-3, MCF-7and EC9706cell lines and some showed promising anticancer activity for certain cancer cell lines. Among them,5i,5n,6f and6k showed significant inhibitory activity against all the three human cell lines. Especially, the bis-steroidal triazolopyrimidine6k exhibited the best inhibitory activity against all the three human cell lines, which is worth further investigation.