Synthesis and pharmacological evaluation of pyrazolopyrimidopyrimidine derivatives: anti-inflammatory agents with gastroprotective effect in rats.
We report the synthesis of new anti-inflammatory 1,7-dihydropyrazolo[3',4':4,5]pyrimido[1,6-a]pyrimidine5from aminocyanopyrazole. All compounds were characterized by physical, chemical and spectral studies. Preliminary pharmacological evaluation of the resulting products showed that compounds5a,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,5fwhich exhibited the most potent anti-inflammatory activity. In addition, the compounds5a,b,fshowed a significant gastroprotective effect against HCl/EtOH-induced gastric ulcer.
Laboratoire de Chimie Appliquée, Hétérocycles, Corps Gras et Polymères, Faculté des Sciences de Sfax, Université de Sfax, 3018 Sfax, Tunisia.
Amine
A
Karoui
Laboratoire de Chimie Appliquée, Hétérocycles, Corps Gras et Polymères, Faculté des Sciences de Sfax, Université de Sfax, 3018 Sfax, Tunisia.
Fatma
F
Allouche
Unité de Recherche des Substances Actives Marines (URSAM), Laboratoire de Pharmacologie, Faculté de Pharmacie, Université de Monastir, 5000 Monastir, Tunisia.
Monia
M
Deghrigue
Laboratoire de Chimie Appliquée, Hétérocycles, Corps Gras et Polymères, Faculté des Sciences de Sfax, Université de Sfax, 3018 Sfax, Tunisia.
Asma
A
Agrebi
Unité de Recherche des Substances Actives Marines (URSAM), Laboratoire de Pharmacologie, Faculté de Pharmacie, Université de Monastir, 5000 Monastir, Tunisia.
Abderrahman
A
Bouraoui
Laboratoire de Chimie Appliquée, Hétérocycles, Corps Gras et Polymères, Faculté des Sciences de Sfax, Université de Sfax, 3018 Sfax, Tunisia.
Fakher
F
Chabchoub
Aminocyanopyrazole; Anti-inflammatory; Dihydropyrazolo[3′,4′:4,5]pyrimido[1,6-a]pyrimidine; Gastroprotective; Pyrazolo[3,4-d]pyrimidine