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 A2 receptor antagonists

Abstract 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 A 2 and A 1 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 A 2 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.