Based on the structural differences between cyclooxygenase-2 (COX-2) and COX-1, a series of ibuprofen derivatives was designed, in which, a substituted benzamido group was introduced to the 3 position of the phenyl ring of ibuprofen. The purpose of this modification was to add a structural segment to occupy the side pocket in COX-2 so as to enhance their affinity for COX-2. The twelve target compounds were synthesized in five steps with ibuprofen as the starting material and structurally confirmed by ¹H NMR, MS and elemental analysis (or HRMS). The biological tests showed that some of them have inhibitory activity against COX-2 in vitro. Compounds 7g and 7h were evaluated in vivo and exhibited weak anti-inflammatory but potent analgesic activities.

Key words: ibuprofen, cyclooxygenase-2, inhibitor, anti-inflammatory, analgesic