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

Authors

  • Olga Ya. Shyyka Department of Organic Chemistry, Ivan Franko National University of Lviv, 6 Kyryla i Mefodiya St., Lviv 79005, Ukraine
  • Nazariy T. Pokhodylo Department of Organic Chemistry, Ivan Franko National University of Lviv, 6 Kyryla i Mefodiya St., Lviv 79005, Ukraine
  • Vitalii A. Palchykov Oles Honchar Dnipro National University, Research Institute of Chemistry and Geology, 72 Gagarin Ave., Dnipro 49010, Ukraine University of Texas at Dallas, Department of Chemistry and Biochemistry, 800 W. Campbell Road, Richardson, Texas 75080, USA
  • Nataliya S. Finiuk Institute of Cell Biology of National Academy of Sciences of Ukraine, 14/16 Drahomanov St., Lviv 79005, Ukraine
  • Rostyslav S. Stoika Institute of Cell Biology of National Academy of Sciences of Ukraine, 14/16 Drahomanov St., Lviv 79005, Ukraine
  • Mykola D. Obushak Department of Organic Chemistry, Ivan Franko National University of Lviv, 6 Kyryla i Mefodiya St., Lviv 79005, Ukraine

DOI:

https://doi.org/10.1007/5576

Keywords:

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

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.

Downloads

Published

2020-07-10

Issue

Vol. 56 No. 6 (2020): Heterocyclic сompounds in medicinal chemistry

Section

Original Papers