Abstract
A regioselective synthetic route to 2,8-disubstituted pyrido[3,4-b ]pyrazines, by initial condensation
reaction between suitable diaminopyridines and α-keto aldehydes
equivalents, has been developed. Focusing on the functionalization
on C-8, 2-aryl-8-bromo- and 8-amino-2-arylpyrido[3,4-b ]pyrazines have been synthesized.
Anilines, amides, and ureas have been introduced at the 8-position
from key intermediates. 2,8-Disubstituted pyrido[3,4-b ]pyrazines thus prepared were
found to be of biological interest.
Key words
pyrido[3,4-b ]pyrazines
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Kinase Inhibition
Assay : Recombinant kinases were purchased
from Millipore or ProQinase. AlphaScreen Bead Kits from Perkin-Elmer
were used to quantify the kinase activity. For the assessment of
IC50 values, compounds were tested at 10 final concentrations
between 3.16 nM and 100 µM. Kinase, 10 µM ATP,
kinase substrate, and the test compound were incubated for 1 h on
a 384-well Optiplate in a final volume of 15 µl. The kinase
reaction was stopped by adding 10 µl ALPHA-Beadmix. The
read out was done on the next morning using an Envision reader (PerkinElmer). IC50 values
were calculated using Graph Pad Prism software.
