A quantitative structure-activity relationship study of ligands exhibiting agonist and antagonist actions with cholecystokinin-receptors.

Observed biological activities of substituted phenyl urea/thiourea tetrapeptides as agonists with the cholecystokinin-alimentary canal (CCK-A) receptor, and (R)-4-benzamido-5-oxopentanoic acid derivatives with both peripheral (CCK-A) and the central (CCK-B) (brain) receptors have been shown to be correlated with various physicochemical, e.g. pi, sigma, and structural, e.g. Vw and dummy, I, parameters. These results were, then interpreted to predict promising criteria for having ligands with better affinity with the CCK receptors.

Structure-activity relationship studies of 4-substituted-2-guanidinothiazoles: reversible inhibitors of gastric (H+/K+)-ATPase.

The role of physicochemical factors, electronic and hydrophobic, and a hydrogen donor index in the inhibition of gastric (H+/K+)-ATPase by 4-phenyl-2-guanidinothiazoles and the 4-indolyl-2-guanidinothiazoles has been quantitatively analysed. For the first congeneric series, the resonance effect of the ortho- and para-substituents and hydrogen donor property of the meta-substituent in the phenyl ring play crucial role, whereas for 4-indolyl analogues, the hydrophobicity and electron withdrawing effect of X-substituents in the indolyl ring are shown to be important decisive factors. Also the substitution of the guanidine moiety, e.g. by benzyl, raises the activity of proton pump inhibitors. The substitution at 5-position of thiazole ring does not enhance the potency.