SYNTHESIS OF IMIDAZO[1,2-C]PYRAZOLO[4,3-E]PYRIMIDINES, PYRAZOLO[4,3-E]1,2,4-TRIAZOLO[1,5-C]PYRIMIDINES AND 1,2,4-TRIAZOLO[5,1-I]PURINES - NEW POTENT ADENOSINE-A(2)-RECEPTOR ANTAGONISTS

A number of 2- or 4-fluorobenzylderivatives of imidazo[1,2-c]pyrazolo[4,3-e]pyrimidine, pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine and 1,2,4-triazolo[5,1-i] purine have been synthesized. The interaction with the adenosine A2 and A1 receptors was evaluated using selected biological assays . The highest degree of activity was displayed by the 5-amino-2-(2-furyl)-7-(or 8-)-fluorobenzyl-pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine 13e, f and 18e, f and -3-fluorobenzyl-1-2-4-triazolo[5,1-i] purines 19e, f. The compound 18f was found to be the most potent A2 antagonist in our series with a selectivity similar to that of the reference compound CGS 15943, but with 75-fold more activity in the platelet aggregation model.