1. Department of Pharmaceutical Chemistry, Semmelweis University, H?gyes Endre u. 9, 1092 Budapest, Hungary;2. Vichem Chemie Research Ltd., Herman Ottó u. 15., 1022 Budapest, Hungary
Abstract:
Cyclin-dependent kinases (CDKs) and Polo-like kinases (PLKs) play key role in the regulation of the cell cycle. The aim of our study was originally the further development of our recently discovered polo-like kinase 1 (PLK1) inhibitors. A series of new 2,4-disubstituted pyrimidine derivatives were synthesized around the original hit, but their PLK1 inhibitory activity was very poor. However the novel compounds showed nanomolar CDK9 inhibitory activity and very good antiproliferative effect on multiple myeloma cell lines (RPMI-8226).
