Study On The Design, Synthesis And Antitumor Activity Of Cyanidene 3 - N - Containing Heterocyclic Derivatives

As a novel tumor angiogenesis inhibitor,2-Methoxyestradiol (2ME2,1) has progressed into clinical trials phase III for treatment of various solid cancers, especially of breast cancer, ovarian cancer, prostate cancer and multiple myeloma.In our past research, a series of non-steroidal analogues of 2ME2 were designed and synthesized, which involved in the scaffolds of 3-phenyl-2H-chromen-2-one, 3-phenyl-4H-chromen-4-one and stilbenes. According to the bioactivity screening data of 2H-chromen-2-ones with different aza-cyclic rings in position 3, it could be concluded that an aromatic ring in 3-position may be the essential pharmacophore for their anti-tumor activities.In this study, two series of target compounds were designed and synthesized to validate the mentioned presumption therefore. Series 1 was focued on further extension of 2H-chromen-2-ones by introducing more aza-cycles into 3-position, including both saturated and aromatic rings. Especially,3-(pyrrol-1-yl)-and 3-(2,5-dihydropyrrol-l-yl)-2H-chromen-2-one would be paid more attention owing to the peculiar structural difference between them. Series 2 shown the scaffold as 4H-chromen-4-one. All kinds of aza-cycles as in series 1 were designed to be introduced systematically into the corresponding position in order to investigate the effect of 3-substituents on different skeletons.As a result, some of the target compounds have been screened against the cell lines of HUVEC, RL95-2, SKOV-3, MCF-7 and T-47D. However, the bioactivity assay of the others and some important intermediates are still in performance. The SAR will be concluded and discussed completely after the total bioactivity data obtained.