A Quantitative Structure - Activity Relationship Study of Novel Inhibitors of Cyclooxygenase - 2 : The 5 - Aryl - 2 , 2 - dialkyl - 4 - phenyl - 3 ( 2 H ) furanone Derivatives
نویسنده
چکیده
The cyclooxygenase-2 enzyme inhibition activity of 5-aryl-2,2-dialkyl-4-phenyl-3(2H)furanone derivatives is quantitatively analyzed through Fujita-Ban and Hansch type of approaches. The analyses have helped to ascertain the role of different substituents in explaining the observed inhibitory activity of these congeners. From both approaches it is revealed that more hydrophobic susbtituents at 4-R 1 , a non-hydrogen bond acceptor substitutent, preferably a -F substituent, at 3-R 1 in 4-phenyl ring of 3(2H)furanone scaffold improve inhibitory action of a compound. The substituents exhibiting collective molecular bulk smaller than spirocyclopentyl at X and Y positions are preferred as these geminal positions seems to be involved in steric interation. Similarly, 4-aminosulfonyl in 5 aryl ring of 3(2H)furanone moiety emerged as a better choice than 4-methylsulfonyl substitution.
منابع مشابه
3D-QSAR CoMFA/CoMSIA studies on 5-aryl-2,2-dialkyl-4-phenyl-3(2H)-furanone derivatives, as selective COX-2 inhibitors.
Comparative Molecular Field Analysis (CoMFA) and Comparative 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. Rem...
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