We report the synthesis of new anti-inflammatory 1,7-dihydropyrazolo[3′,4′:4,5]pyrimido[1,6-a]pyrimidine 5 from aminocyanopyrazole. All compounds were characterized by physical, chemical and spectral studies. Preliminary pharmacological evaluation of the resulting products showed that compounds 5a, b, f (50–100 mg/kg, i.p) are active anti-inflammatory agents in carrageenan-induced rat paw oedema assay, and their effects are comparable to that of acetylsalicylic–lysine (300 mg/kg, i.p.), used as a reference drug. The nature of substituent (Y, R3) had a pronounced effect on the anti-inflammatory activity. Studies of structure–activity relationships have led to selection of compound ethyl-3,5-dimethyl-7-imino-N1-phenyl-1,7-dihydropyrazolo[3′,4′:4,5]pyrimido[1,6-a]pyrimidine-6-carboxylate, 5f which exhibited the most potent anti-inflammatory activity. In addition, the compounds 5a, b, f showed a significant gastroprotective effect against HCl/EtOH-induced gastric ulcer.

A straightforward method has been developed for the synthesis of new anti-inflammatory 1,7-dihydropyrazolo [3,4-d] imidazo[1,2-f]pyrimidine 5 from aminocyanopyrazole. These compounds were screened for their anti-inflammatory, gastroprotective, analgesic, antioxidant and anticandidal activities. Studies of structure-activity relationships have led to selection of compound 6-(4-methoxyphenyl)-3-methyl-1,7-dihydropyrazolo[3,4-d]imidazo[1,2-f]pyrimidine, 5a which exhibited the most potent activities. The structures of all new compounds were elucidated using IR, 1 H NMR, 13 C NMR and HRMS.

No abstract