2,6,8,9-tetrasubstituted purines as new CDK1 inhibitors.
Purine inhibitors of cyclin-dependent kinases attract attention as potential anticancer drugs because their first representative roscovitine recently entered clinical trials. Although well described in terms of structure-activity relationships, we still present here a novel modification of the purine scaffold influencing their inhibitory properties. The introduced C-8 substituents, however, lowered the CDK inhibitory activity of roscovitine, whereas the antiproliferative potential of several derivatives remained high.
Moravec
Jirí
J
Isotope Laboratory, Institute of Experimental Botany, Academy of Sciences of the Czech Republic, Vídenská 1083, 14220 Prague 4, Czech Republic.
Krystof
Vladimír
V
Hanus
Jan
J
Havlícek
Libor
L
Moravcová
Daniela
D
Fuksová
Kvetoslava
K
Kuzma
Marek
M
Lenobel
René
R
Otyepka
Michal
M
Strnad
Miroslav
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D011485:Protein Binding; D011687:Purines / Q000138:chemical synthesis* / Q000494:pharmacology; D000077546:Roscovitine; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011687:Purines; D000077546:Roscovitine; D016203:CDC2 Protein Kinase