Synthesis and Evaluation of Biological Activities of Thieno-[2,3-d]-pyrimidine Derivatives

A series of novel thieno[2,3-d]pyrimidine derivatives were designed, synthesized and evaluated for their biological ability. 2-Amino-4,7-dihydro-5H-thieno[2,3-d]pyrano-3-cyanonitrile was synthesized by Gewald reaction using pyranone as substrate, malonitrile and sulfur powder as raw materials and triethylamine as base at room temperature. Subsequent amination with N,N-dimethylformamide dimethyl acetal (DMF-DMA) gave N'-(3-cyano-4,7-dihydro-5H-thieno[2,3-c]pyran-2-yl)-N,N-dimethylmethanimidamide. In this article, the 23 thieno[2,3-d] pyrimidines were obtained by Dimroth rearrangement condensation with different anilines, 16 of them being new compounds. Meanwhile, all compounds were assessed for breast cancer MDA-MB-231 cell line bioactivity with paclitaxel (PTX) as the positive control, and all compounds in the series showed inhibitory effects on breast cancer cell MDA-MB-231. The IC₅₀ of compound l against MDA-MB-231 is 27.6 μM, which is similar to that of PTX with an IC₅₀ of 29.3 μM. This means that compound l exhibits comparable inhibitory activity to PTX in MDA-MB-231 cells and may be considered as a potential anti-MDA-MB-231 inhibitor.

Keywords: thieno[2,3-d]pyrimidine derivatives; Dimroth rearrangement; Gewald reaction; antitumor; microwave synthesis