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 ha s been quantitatively analysed. For the first congeneric series, the r esonance 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 electro with drawing effect of X-substituents in the indolyl ring are shown to be i mportant decisive factors. Also the substitution of the guanidine moie ty, e.g. by benzyl, raises the activity of proton pump inhibitors. The substitution at 5-position of thiazole ring does not enhance the pote ncy.