Three-Dimensional Quantitative Structural Activity Relationship (3D-QSAR) Studies of Some 1,5-Diarylpyrazoles: Analogue Based Design of Selective Cyclooxygenase-2 Inhibitors

[摘要] Selective cyclooxygenase inhibitors have attracted much attention in recent times in the design of new non-steroidal anti-inflammatory drugs (NSAID). 3D-QSAR studies have been performed on a series of 1,5-diarylpyrazoles that act as selective cyclooxygenase-2 (COX-2) inhibitors, using three different methods: comparative molecular field analysis (CoMFA) with partial least squares (PLS) fit; molecular field analysis (MFA) and; receptor surface analysis (RSA) with genetic function algorithms (GFA). The analyses were carried out on 30 analogues of which 25 were used in the training set and the rest considered for the test set. These studies produced reasonably good predictive models with high cross-validated and conventional r² values in all the three cases.

[关键词] NSAID design;selective COX-2 inhibitors;3D-QSAR;CoMFA;MFA;RSA