1,2-Diarylimidazoles as inhibitors of cyclooxygenase-2: a quantitative structure-activity relationship study.
The cyclooxygenase-2 (COX-2) enzyme inhibition activity of derivatives of 1,2-diarylimidazole is analysed through Fujita-Ban and Hansch approaches. The analyses have helped to ascertain the role of different substituents in explaining the observed inhibitory potency of these analogues. From both approaches it is revealed that the more hydrophobic X-substitutions that are present at the 3- and 4-positions of the aryl ring and are also non-hydrogen acceptor in character improve inhibitory action of a compound. The smaller substituent either H or F is preferred at the 2-X position as it is involved in steric interaction. Likewise, the substituent-NH2 instead of Me at R is advantageous. Further, for a data set of 35 congeners, the selectivity ratio related to the constitutive COX-1 isozyme is also analysed through the Fujita-Ban approach. The derived contributions of parent moiety and various substituents have helped to predict the substitution pattern in the design of more effective compounds that were not in the original data set.
Singh
P
P
Department of Chemistry, S.K. Government College, Sikar, India.
Kumar
R
R
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015195:Drug Design; D007093:Imidazoles / Q000494:pharmacology*; D007527:Isoenzymes / Q000187:drug effects*; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007093:Imidazoles; D007527:Isoenzymes; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases