Synthesis and biological activity evaluation of novel 3,5,7-trisubstituted pyrazolo[1,5-a]pyrimidines
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
36496201
DOI
10.1016/j.bmcl.2022.129096
PII: S0960-894X(22)00572-8
Knihovny.cz E-zdroje
- Klíčová slova
- Acute myeloid leukemia, Antitumour activity, FLT3, Pyrazolo[1,5-a]pyrimidines,
- MeSH
- akutní myeloidní leukemie * farmakoterapie MeSH
- apoptóza MeSH
- inhibitory proteinkinas chemie MeSH
- lidé MeSH
- mutace MeSH
- nádorové buněčné linie MeSH
- proliferace buněk MeSH
- pyrimidiny * chemie MeSH
- simulace molekulového dockingu MeSH
- tyrosinkinasa 3 podobná fms genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- inhibitory proteinkinas MeSH
- pyrimidiny * MeSH
- tyrosinkinasa 3 podobná fms MeSH
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.
Citace poskytuje Crossref.org
