Synthesis and biological activity evaluation of novel 3,5,7-trisubstituted pyrazolo[1,5-a]pyrimidines

Autor:	Kristýna Vlková, Růžena Padrtová, Tomáš Gucký, Miroslav Peřina, Eva Řezníčková, Vladimír Kryštof
Rok vydání:	2023
Předmět:	Organic Chemistry Clinical Biochemistry Drug Discovery Pharmaceutical Science Molecular Medicine Molecular Biology Biochemistry
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 80:129096
ISSN:	0960-894X
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::640dca68144abfacce1d8813ece67700 https://doi.org/10.1016/j.bmcl.2022.129096 Zobrazit plný text záznamu Full Text from ScienceDirect