DIARYLSPIRO[2.4]HEPTENES AS SELECTIVE CYCLOOXYGENASE-2 INHIBITORS - AQUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP ANALYSIS

Both the Fujita-Ban and Hansch quantitative structure-activity relatio nship (QSAR) analyses, attempted on the data set of 5,6-diarylspiro[2. 4]hept-5-enes as the inhibitors of cyclooxygenase-2 (COX-2) have helpe d to ascertain the role of R- and X-substituents in explaining their o bserved biological inhibition actions. From both approaches it is conc luded that the substitution NH2 instead of Me at R is desirable. In ad dition, the 3-F and/or 5-Cl having smaller molar refraction values and the 4-Cl and 4-CF3 possessing less hydrophobic-cum-hydrogen acceptor property at X are the preferred substitutions of the aryl ring. For th ose analogues whose COX-1 inhibition data are available, the selectivi ty ratio, -logS [S = IC50(COX-2)/IC50(COX-1)], is found to correlate w ith the electronic and hydrophobic-cum-hydrogen acceptor parameters. F rom the derived significant correlation, it follows that the higher el ectron-withdrawing effect produced by 3- and 4-X and the lower hydroph obic-cum-hydrogen accepting effect by 4-X in the aryl ring are highly beneficial.