Synthesis and enzymic activity of 6-carbethoxy- and 6-ethoxy-3,7-disubstituted pyrazolo[1,5-a]pyrimidines and related derivatives as adenosine cyclic 3',5'-phosphate phosphodiesterase inhibitors

Abstract

A number of 3,7-disubstituted 6-carbethoxypyrazolo[1,5-a]pyrimidines and 3,7-disubstituted 6-ethoxypyrazolo-[1,5-a]pyrimidines were prepared and evaluated as cAMP phosphodiesterase (PDE) inhibitors vs. the low Km enzyme isolated from beef heart, rabbit lung and kidney preparations. The results were between 0.5-13 times as potent as theophylline as inhibitors of PDE, depending on the tissue source. A number of these PDE inhibitors exhibited significant physiological effects in guinea pigs, mice and rats. Selective PDE inhibition in various tissues should be possible. Several of these heterocycles were superior to adenosine in inhibiting ADP-induced platelet aggregation in vitro.