One of approaches to reducing NSAIDs (nonsteroidal antiinflammatory drugs)-associated gastrointestinal adverse is to convert NSAIDs into selective COX-2 inhibitors by structural modifications. However recent observations indicate that the expression of COX-2 appears to be required for ovulation and fertilization. This implicates that the optimal compromise between the beneficial and the deleterious effects of selective COX-2 inhibitors should be made for the treatment of inflammation. In the present paper the molecular mechanism of a series of Flurbiprofen derivatives targeting towards COX-1 and COX-2 was explored by application of DOCK 4.0 program and minimization method. The significant correlation between compound selectivity ( COX-2 vs COX-1) and the difference of docking energy [ΔE_(cox-2) - ΔE_(cox-i)] provides some insights into that the substituents in the distal phenyl ring have no positive effect on the binding to both COX-1 and COX-2 compared with Flurbiprofen. However, the COX-2 selectivity has been effectively improved. Expansion of the approach may be envisioned for the modification of other COX inhibitors containing phenyl ring binding at this pocket.

Key words: cyclooxygenase, flurbiprofen, INHIBITOR, FREE ENERGY