Quantitative structure-activity relationship study of orally active cyclooxygenase-2 (COX-2) inhibitors of derivatives of 3-phenoxypyran-4-one

The cyclooxygenase (COX) inhibition activities of the derivatives of 3-phenoxypyran-4-one were analyzed through multiple-regression analysis (MRA). Appropriate physicochemical parameters, identified for the substitutents of phenyl ring, attached to 3-phenoxypyran-4-one moiety were quantitatively correlated with COX-2 and COX-1 inhibition activities of these compounds. The derived significant correlation equation for COX-2 inhibition suggested that the ortho-substituent with negative resonance parameter, the para-substituent with lower dipole moment and the meta-substituent having higher resonance parameter were advantageous for the activity. The derived correlation equation for COX-1 inhibition suggested the significance of resonance effect for ortho-substituents and electron-donating effect for para-substituent. A few potential congeners were also suggested for further synthesis.