Synthesis and biological activity of fluorinated 7-aryl-2-pyridyl-6,7-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-amines.
MetadataShow full item record
In our lead finding program, 12 new fluorinated 7-aryl-2-pyridyl-6,7-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-amines were prepared via a practical three-step procedure starting from (iso)nicotinic hydrazides. The fluorine substituted aryl fragment was introduced in the last step through cyclocondensation of N-(3-pyridyl-1,2,4-triazol-5-yl)guanidines and fluoro/trifluoromethyl substituted benzaldehydes. The structures of the compounds were confirmed by 1H and 13C NMR spectral data. The tautomeric preferences for the compounds were established using 2D NOESY experiments. The antiproliferative activity of the synthesized 1,2,4-triazolo[1,5-a][1,3,5]triazines was evaluated against breast, colon and lung cancer cell lines. The highest antiproliferative activity in the series was found for 2-(pyridine-3-yl)-7-(4-trifluoromethylphenyl)-6,7-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-amine. The lack of inhibitory activity against bovine dihydrofolate reductase (DHFR) indicated that the antiproliferative activity was realized via other mechanisms.
NOTICE: This is the author's version of a work that was accepted for publication in Journal of Fluorine Chemistry. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Fluorine Chemistry, 129, 5, 2008. DOI: 10.1016/j.jfluchem.2008.02.007
Showing items related by title, author, creator and subject.
Dolzhenko, Anton; Dolzhenko, A.; Chui, W. (2007)The substitution of hydrogen by fluorine as bioisosteric replacement has been practised widely in agricultural and medicinal chemistry. This has led to the discovery of many pesticides and therapeutically useful chemical ...
Synthesis and biological activity of fluorinated 7-benzylamino-2-phenyl-1,2,4-triazolo[1,5-a][1,3,5]triazin-5-aminesDolzhenko, Anton; Tan, B.; Chiu, G.; Chui, W.; Dolzhenko, A. (2015)New fluorinated 7-benzylamino-2-phenyl-1,2,4-triazolo[1,5-a][1,3,5]triazin-5-amines were designed as potential anticancer agents and a practical method for their preparation was developed. The reaction of benzhydrazide ...
A structure-activity relationship study of 1,2,4-triazolo[1,5-a][1,3,5] triazin-5,7-dione and its 5-thioxo analogues on anti-thymidine phosphorylase and associated anti-angiogenic activitiesBera, H.; Tan, B.; Sun, L.; Dolzhenko, Anton; Chui, W.; Chiu, G. (2013)Thirty-three 1,2,4-triazolo[1,5-a][1,3,5]triazin-5,7-dione and its 5-thioxo analogues were designed and synthesized which contained different substituents at meta- and/or para-positions of 2-phenyl or 2-benzyl ring attached ...