Pyrazolo [3,4-d] pyrimidines, a new class of adenosine antagonists.

A variety of nitrogen heterocycles structurally related to caffeine and theophylline have been tested for activity as adenosine receptor antagonists. Preliminary screening, utilizing displacement of [3H]N6-phenylisopropyladenosine binding to rat brain membrane A1-adenosine receptors, identified several pyrazolo[3,4-d]pyrimidines with potential antagonist activity. These were then tested for their ability to antagonize the adenosine-stimulated adenylate cyclase system of guinea-pig brain slices. One of these, 4,6-bis-alpha-carbamoylethylthio-1-phenylpyrazolo[3,4-d]pyrimidine (DJB-KK), was over an order of magnitude more potent than theophylline in blocking adenosine-stimulated increases in cyclic AMP levels.