1. Pyrazolo[3,4-d]pyrimidine derivatives as COX-2 selective inhibitors: synthesis and molecular modelling studies
- Author
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RAFFA, Demetrio, MAGGIO, Benedetta, PLESCIA, Fabiana, CASCIOFERRO, Stella Maria, RAIMONDI, Maria Valeria, PLESCIA, Salvatore, CUSIMANO, Maria Grazia, Raffa, D, Maggio, B, Plescia, F, Cascioferro, SM, Raimondi, MV, Plescia, S, and Cusimano, MG
- Subjects
Models, Molecular ,Sulfonamides ,Sheep ,Cyclooxygenase 2 Inhibitors ,Indomethacin ,Anti-Inflammatory Agents ,Settore CHIM/08 - Chimica Farmaceutica ,Structure-Activity Relationship ,4(3H)-Quinazolinone ,Pyrimidines ,Docking, Pyrazolo[3,4-d]pyrimidine ,Cyclooxygenase 1 ,Animals ,Humans ,Pyrazoles ,Computer Simulation ,COX-2 inhibitor ,Nitrobenzenes - Abstract
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.
- Published
- 2009