Quantitative structure-activity relationship studies of inhibitors of gastric (H+/K+) -ATPase
Singh, P.; Sharma, R.C.; Ojha, T.N.
Drug Design and Delivery 7(2): 131-138
1991
ISSN/ISBN: 0884-2884 PMID: 1832864 Document Number: 382349
The (H+/K+)-ATPase enzyme inhibitory activity of omeprazole analogues (Figure 1) and 1-aryl-4-methyl-2,3-dihydropyrrolo[3,2-c]quinolines (Figure 2) was found to be significantly correlated with electronic (sigma) or pKa parameter that governs the basicity of the molecules. The former compounds are representative of irreversible blockers, and the latter of reversible blockers. Inclusion of hydrophobic (pi) and/or steric (Es) parameters sometimes led to improvement in the correlations, suggesting that these parameters may play a role in the formation of a cyclic intermediate. The derived significant correlation equations strongly support a mechanism of action, first proposed by Lindberg et al., involving such a cyclic intermediate.