Cage-Like Amines in the Green Protocol of Transannular Thieno[2,3-d]Pyrimidinone Formation as Promising Anticancer Agents

• DOI: 10.1007/s10593-020-02732-2
• Publication Date: 2020-07-18T05:19:10Z
• Authors: Olga Ya. Shyyka; Nazariy T. Pokhodylo; Vitalii A. Palchykov; Nataliya S. Finiuk; Rostyslav S. Stoika; Mykola D. Obushak
• Keywords: 01 natural sciences; 0104 chemical sciences

Cage-like amines with norbornane and adamantane frameworks were studied in a versatile, convenient one-pot green synthetic experiment for pyrimidine core annulation via cleavage of a 1H-tetrazole ring. The transannulation was performed without an excess of the reagents and solvent under optimized conditions. As a result, 11 new thieno[2,3-d]pyrimidinones with bulky substituents were obtained in high yields without the need of further purification and with excellent selectivity of the process. The introduced сage-like framework is regarded as a bioisostere of the 2-arylamino moiety. Preliminary screening of the biological activity was performed and 2-{[1-(bicyclo[2.2.1]heptan-2-yl)ethyl]amino}-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one demonstrated high toxicity toward human leukemia HL-60, cervix carcinoma KB3-1, and colon carcinoma HCT116 cells that correlates well with the results obtained previously for the activity of the compounds with benzylamino substituents.