Synthesis, cyclooxygenase inhibition, anti-inflammatory evaluation and ulcerogenic liability of new 1-phenylpyrazolo[3,4-d]pyrimidine derivatives

Abstract

A new group of 1-phenylpyrazolo[3,4-d]pyrimidine derivatives 14a–d–21 were synthesized from 2-(6-methyl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)acetohydrazide (12). All the synthesized compounds were evaluated for their cyclooxygenase (COX) inhibition, anti-inflammatory activity and ulcerogenic liability. All the target compounds were more potential in inhibiting COX-2 than COX-1. Compounds having pyrazolyl moiety in a hybrid structure with pyrazolo[3,4-d]pyrimidine scaffold (14a–d, 16 and 17) showed higher edema inhibition percentage activities (34–68%) and the 5-aminopyrazole derivative (14c, ED50=87.9 μmol/kg) was the most potent one > celecoxib (ED50=91.9 μmol/kg). While, the in vivo potent compounds (14a–d, 16, 17 and 21) caused variable ulceration effect (ulcer index= 0.33–4.0) comparable to that of celecoxib (ulcer index = 0.33), the pyrazol-3-one derivative (16) and the acetohydrazide (21) were the least ulcerogenic derivatives showing the same ulcerogenic potential of celecoxib.