Pyrazolo[3,4-d]pyrimidine derivatives as COX-2 selective inhibitors: synthesis and molecular modelling studies.
The pyrazolo[3,4-d]pyrimidine system shows a multitude of interesting pharmacological properties. Owing to the potential anti-inflammatory activity of 5-benzamido-pyrazolo[3,4-d]pyrimidin-4-one derivatives and considering the easy synthesis of this class of compounds, a set of new 5-benzamido-1H-pyrazolo[3,4-d]pyrimidin-4-ones has been prepared in 42-80% yields by reacting 5-aminopyrazole-4(N-benzoyl)carbohydrazide derivatives and the opportune triethylorthoesters. Compounds 8a, b, 10a-d, and 11a, b revealed a superior inhibitory profile against COX-2, when compared to that of reference standards NS398 and indomethacin. Molecular modelling studies confirmed the obtained biological results.
Raffa
Demetrio
D
Dipartimento di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo, Palermo, Italy. demraffa@unipa.it
Maggio
Benedetta
B
Plescia
Fabiana
F
Cascioferro
Stella
S
Raimondi
Maria Valeria
MV
Plescia
Salvatore
S
Cusimano
Maria Grazia
MG
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D003198:Computer Simulation; D051545:Cyclooxygenase 1 / Q000187:drug effects / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008958:Models, Molecular; D009578:Nitrobenzenes / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000494:pharmacology*; D012756:Sheep; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D009578:Nitrobenzenes; D011720:Pyrazoles; D011743:Pyrimidines; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; C014175:pyrazolo(3,4-d)pyrimidine; D051545:Cyclooxygenase 1; D007213:Indomethacin