{Reference Type}: Journal Article
{Title}: Synthesis and biological activity evaluation of novel 3,5,7-trisubstituted pyrazolo[1,5-a]pyrimidines.
{Author}: Vlková K;Padrtová R;Gucký T;Peřina M;Řezníčková E;Kryštof V;
{Journal}: Bioorg Med Chem Lett
{Volume}: 80
{Issue}: 0
{Year}: 01 2023 15
{Factor}: 2.94
{DOI}: 10.1016/j.bmcl.2022.129096
{Abstract}: Mutation of FLT3 protein kinase is often associated with deregulated cell proliferation in acute myeloid leukemia and the inhibition of this kinase is a potential therapeutic strategy. We report a novel series of 3,5,7-trisubstituted pyrazolo[1,5-a]pyrimidines prepared in an effort to study their biological activity particularly toward FLT3-ITD and its downstream regulators as well as toward CDK2 and CDK9. Derivative 10b was capable to strongly inhibit all kinases and its selectivity in FLT3-ITD expressing cell lines MOLM13 and MV4-11 was in line with FLT3-ITD inhibition. Further biochemical analyses and molecular docking confirmed FLT3 as a cellular target of 10b.