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.
A number of 3,7-disubstituted 6-carbethoxypyrazolo [1,5-a] pyrimidines and 3,7-disubstituted 6-ethoxypyrazolo-[1,5-a]pyrimidines have been prepared and evaluated as adenosine cyclic 3',5'-phosphate (cAMP) phosphodiesterase (PDE) inhibitors vs. the low Km enzyme isolated from beef heart, rabbit lung, and kidney preparations. The results were found to be between 0.5 to 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 different animal systems, suggesting it should be possible to obtain selective PDE inhibition in various tissues. Several of these heterocycles were found superior to adenosine in inhibiting ADP-induced platelet aggregation in vitro.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008168:Lung / Q000201:enzymology; D010974:Platelet Aggregation / Q000187:drug effects; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D011817:Rabbits; D013552:Swine
D011720:Pyrazoles; D011743:Pyrimidines; D000244:Adenosine Diphosphate; D015105:3',5'-Cyclic-AMP Phosphodiesterases