Open Access Open Access  Restricted Access Subscription Access

CAGE-LIKE AMINES IN THE GREEN PROTOCOL OF TRANSANNULAR THIENO[2,3-d]PYRIMIDINONE FORMATION AS PROMISING ANTICANCER AGENTS

Olga Ya. Shyyka, Nazariy T. Pokhodylo, Vitalii A. Palchykov, Nataliya S. Finiuk, Rostyslav S. Stoika, Mykola D. Obushak
Cover Image

Abstract


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.


Keywords


1H-tetrazoles; thienopyrimidines; cage-like compounds; cytotoxic activity; human tumor cells; tetrazole cleavage; transannulation.

Full Text: PDF Supplementary File(s): supplementary info (4MB)


 

 

Latvian Institute of Organic Synthesis - Aizkraukles iela, 21, Riga, LV-1006, Latvia - hgs@osi.lv