Comparative Molecular Field Analysis (CoMFA) and Com- parative Molecular Similarity Indices Analysis (CoMSIA)

were performed on a series of 5-aryl-2,2-dialkyl-4-phenyl--3(2H)-furanone derivatives, as selective cyclooxygenase--2 (COX-2) inhibitors. Ligand molecular superimposition on the template structure was performed by the atom/ shape based root mean square fit and database alignment methods. Removal of three outliers from the initial train-ing set of 49 molecules improved the predictivity of the model. The statistically significant model was establish-ed of 36 molecules, which were validated by a test set of ten compounds. The atom and shape based root mean square alignment (IV) yielded the best predictive CoMFA model R2cv = 0.664, R2 (non-cross-validated square of correlation coefficient) = 0.916, F value = 47.341, R2bs = 0.947 with six components, standard error of prediction36 = 0.360 and standard error of estimate36 = 0.180 while the CoMSIA model yielded R2cv = 0.777, R2 (non-cross--validated square of correlation coefficient) = 0.905, F va-lue = 66.322, R2bs = 0.933 with four components, standard error of prediction36 = 0.282 and standard error of esti-mate36 = 0.185. The contour maps obtained from 3D--QSAR studies were appraised for activity trends for the molecules analyzed. Results indicate that steric, electro-static, hydrophobic (lipophilic) and hydrogen bond donor substituents play a significant role in COX-2 inhibitory activity and selectivity of the compounds. The data ge-nerated from the present study will further help design novel, potent and selective COX-2 inhibitors