A new pyrazolo pyrimidine derivative inhibitor of cyclooxygenase-2 with anti-angiogenic activity

Abstract

In a previous study, we reported a new pyrazolo pyrimidine derivative, N4 -benzyl-N6 ,N6 -dimethyl-1-1(tert-butyl)-1H-pyrazolo[3,4- d]pyrimidine-6,4-diamine (DPP), which inhibited potently cyclooxygenase-2 activity in intact cell assays with minor activity against cyclooxygenase-1 (IC50 = 0.9 nM for cyclooxygenase-2 versus IC50 = 59.6 nM for cyclooxygenase-1). In the present work, this behaviour was confirmed in vivo by using the 24-h zymosan-injected mouse air pouch model (ID50 = 1.36 nmol/pouch for prostaglandin E2 level). We also studied the possible beneficial effect of DPP in the angiogenesis-dependent murine air pouch granuloma and rat paw carrageenan induced hyperalgesia models. DPP exerted analgesic and anti-angiogenic (52% reduction in angiogenesis at 10 mg/kg, i.p.) effects that may be associated with inhibition of cyclooxygenase-2 activity