Synthesis and biological evaluation of pteridine and pyrazolopyrimidine based adenosine kinase inhibitors

Three new approaches have been tested to modify existing pyridopyrimidine and alkynylpyrimidine classes of nonnucleoside adenosine kinase inhibitors 2 and 3. 4-Amino-substituted pteridines 8a–e were generally less active than corresponding 5- and 6-substituted pyridopyrimidines 2. Pyrazolopyrimidine 13c with IC50=7.5 nM was superior to its open chain alkynylpyrimidine analog 13g (IC50=22 nM) while pyrrolopyrimidines such as 17a were inactive.