AMINO-SUBSTITUTED 1,8-NAPHTHYRIDINES AND PYRIDO[2,3-D]PYRIMIDINES - NEW COMPOUNDS WITH AFFINITY FOR A(1)-ADENOSINE AND A(2)-ADENOSINE RECEPTORS

Two novel classes of adenosine receptor (AR) antagonists, 4-amino-1,8- naphthyridines and 5-aminopyrido[2,3-d]pyrimidines, have been identifi ed and investigated in radioligand binding assays. The compounds exhib it affinities for A(1) and A(2a) AR of rat brain in the micromolar ran ge. 1,8-Naphthyridines are non-selective, or somewhat selective for ei ther A(1)- or A(2) AR. Pyrido[2,3-d]pyrimidines are several-fold selec tive for A(1) AR, the most potent and selective compound being 2,3,4-t etrahydropyrido-[2,3-d]pyrimidine-2,4-dione (12) with a K-i value of 1 .8 mu M at A(1) AR and greater than 10-fold A(1)-selectivity.