title: 2,6,8,9-tetrasubstituted purines as new CDK1 inhibitors.
abstract: 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.
authors.affiliation: Isotope Laboratory, Institute of Experimental Botany, Academy of Sciences of the Czech Republic, Vídenská 1083, 14220 Prague 4, Czech Republic.
authors.forename: Jirí
authors.initials: J
authors.lastname: Moravec
authors.forename: Vladimír
authors.initials: V
authors.lastname: Krystof
authors.forename: Jan
authors.initials: J
authors.lastname: Hanus
authors.forename: Libor
authors.initials: L
authors.lastname: Havlícek
authors.forename: Daniela
authors.initials: D
authors.lastname: Moravcová
authors.forename: Kvetoslava
authors.initials: K
authors.lastname: Fuksová
authors.forename: Marek
authors.initials: M
authors.lastname: Kuzma
authors.forename: René
authors.initials: R
authors.lastname: Lenobel
authors.forename: Michal
authors.initials: M
authors.lastname: Otyepka
authors.forename: Miroslav
authors.initials: M
authors.lastname: Strnad
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011687:Purines; D000077546:Roscovitine; D016203:CDC2 Protein Kinase