Exploring selectivity requirements for COX-2 versus COX-1 binding of 3,4-Diaryloxazolones using E-State index

Considering the importance of developing selective COX-2 inhibitors, the present paper explores selectivity requirements for COX-2 versus COX-1 binding of 3,4-diaryloxazolones using electrotopological state (E-state) index. The study also shows the utility of E-state index in developing statistically acceptable model having direct physicochemical significance: electron density distribution of different atoms of the oxazolone ring and attached two phenyl rings are important for the selective binding with COX-2 over COX-1. Moreover, the use of indicator variable shows that presence of ortho R1 substituent (except fluoro) on the N3-phenyl ring decreases COX-2 selectivity. Further, an amino substituent at R2 position (i.e., sulfonamide compound) is favorable for increasing COX-2 selectivity when the R3 position is unsubstituted.