Novel CDK inhibition profiles of structurally varied 1-aza-9-oxafluorenes.
A series of 1-aza-9-oxafluorenes with functionally varied 3-substituents have been prepared from N-phenoxycarbonyl-4-phenyl-1,4-dihydropyridines and p-benzoquinone and biologically evaluated as inhibitors of various cyclin-dependant kinases. The absence of a 3-hydrogen bond acceptor function leads to a complete loss of inhibitory activity. Differing hydrogen bond acceptor functions surprisingly cause significant shifts in the selectivity of inhibition profiles.
Voigt
Burkhardt
B
Institute of Pharmaceutical Chemistry, Department of Pharmacy, Martin-Luther-University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle, Germany.
Meijer
Laurent
L
Lozach
Olivier
O
Schächtele
Christoph
C
Totzke
Frank
F
Hilgeroth
Andreas
A
D001665:Binding Sites; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis; D005449:Fluorenes / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D005449:Fluorenes; D018844:Cyclin-Dependent Kinases