THREE DIMENSIONAL QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP OF SELECTIVE CYCLOOXYGENASE-2 INHIBITORS

AIM: The discovery of cyclooxygenase-2(COX-2) provides a new target for designing nonsteroidal anti-inflammatory drugs(NSAIDs) with less side effects. A series of inhibitors were analyzed in order to disclose the relationship between activity and structure. METHODS AND RESULTS: Forty four selective COX-2 inhibitors were investigated by means of dock and comparative molecular field analysis(CoMFA). Based upon the active conformation extracted from the SC-558/COX-2 complex all inhibitors were docked into receptor and aligned. The model from dock-CoMFA showed higher ability to explain and predict the activity of selective COX-2 inhibitors, cross-validated R_cv2=0.709, non-cross-validated r²=0.911, F_5,38=75.606, SE=0.242.　CONCLUSION: The combination of dock-CoMFA offers an approach to design new molecule.