Pyrazole is a frequent structural unit in a number of pharmaceuticals and many studies are devoted to the synthesis and biological evaluation of novel pyrazole moiety-bearing molecules. Interestingly, among well studied biologically active annelated pyrazole derivatives, synthetically demanding 2H-pyrazolo [4,3-c]pyridines are relatively unexplored. We recently unraveled potential of variously substituted 2-phenyl-2H-pyrazolo[4,3-c]pyridines as anticancer agents. Therefore, in this study, we further examined the applicability of our synthetic approach and prepared a library of various 6-(2-alkoxyethyl)- and 6-(2-aryloxyethyl)-2H-pyrazolo[4,3-c]pyridines (3) primarily varying by the substituents at the 6-positions in order to assess their biological activity and to formulate possible structure-activity relationships. Functionalization of 2-(2-phenyl-2H-pyrazolo[4,3-c]pyridin-6-yl)ethan-1-ol (2) with various agents afforded a versatile library of 6-substituted 2H-pyrazolo[4,3-c]pyridine compounds 3. Newly prepared heterocyclic compounds 3 were evaluated for their cytotoxicity against K562 cancer cells. The most potent compounds displayed low micromolar GI50 values and caused G2/M cell cycle arrest.

Synthesis and anticancer activity of 6-(2-alkoxyethyl)- and 6-(2-aryloxyethyl)-2-phenyl-2H-pyrazolo[4,3-c]pyridines

ACS Spring Meeting 2021

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