| Abstract [eng] |
Pyrazole is a common structural moiety in many pharmaceuticals, agrochemicals, optoelectronics and dyes. In particular, design and synthesis of new annealed pyrazole derivatives is an important research field in current medicinal chemistry because they demonstrate a wide spectrum of biological activities. The aim of this work was to synthesise novel 2,4,6,7-tetrasubstituted-2H-pyrazolo[4,3-c]pyridines and examine the biological activity and optical properties. 1-Phenyl-3-(2-phenylethynyl)-1H-pyrazole-4-carbaldehyde, which was chosen as a starting material, was prepared from 1-phenyl-1H-pyrazol-3-ol by consecutive alkylation, formylation and Sonogashira cross-coupling reactions. The pyrazolo[4,3-c]pyridine core was obtained via a three step route. Firstly, aldehydes were converted to alcohols using either Gringnard reagents or reduction conditions and then transformed into azide-alkynes. The latter were used in electrophilic cyclization reaction to obtain 7-iodo-4-methyl-2,6-diphenyl-2H-pyrazolo[4,3-c]pyridine and 7-iodo-2,6-diphenyl-2H-pyrazolo[4,3-c]pyridine. The library of 2,4,6,7-tetrasubstituted-2H-pyrazolo[4,3-c]pyridine derivatives was obtained via palladium catalysed cross-coupling reactions. Subsequently, the optical properties of new derivatives were assessed. 7-(4-Methoxyphenyl)-2,6-diphenyl-2H-pyrazolo[4,3-c]pyridine showed the best result with quantum yield value of 71.77%. Furthermore, evaluation of anticancer activity against myelogenous leukemia and breast adenocarcinoma cells showed that the compounds obtained from Suzuki cross-coupling reactions and bearing various aryl substituents at the 7-position appeared to be generally more cytotoxic than compounds, resulting from Buchwald-Hartwig cross-coupling and bearing various anilines in the same 7-position. Noteworthy, compounds bearing no substituents at the 4-position were generally more cytotoxic compared to their methyl counterparts. The most potent compound 7-(4-methoxyphenyl)-2,6-diphenyl-2H-pyrazolo[4,3-c]pyridine exhibited GI50 value of 2.3 μM on leukemia cell line. |
