COMPUTER DESIGN AND SYNTHESES OF ANTIULCER COMPOUNDS - 1ST COMMUNICATION - N-[3-[3-(1-PIPERIDINOMETHYL)PHENOXY]PROPYL]AMINES AND BENZAMIDES

Aiming to develop new antiulcer agents, a quantitative structure-activ ity relationship (QSAR) study on in vitro (pA(2)) and in vivo histamin e H-2-receptor antagonistic activity of a series of N-[3-[3-(1-piperid inomethyl)phenoxy]propyl]amines was carried out using the OASIS comput er system. The results showed that pA(2) increases with the decrease ( increase) of electron donor (acceptor) properties of molecules, partic ularly at the NH-reaction site. The finding is consistent with the ass umption for an increase of histamine H-2-receptor activity of the anta gonists with their ability to form H-bonds with the receptor through N H groups. The correlations with hydrophobicity and related topological indices are consistent with the hypothesis that logP should indirectl y reflect receptor interactions. In addition a series of 3-[3-(1-piper idinomethyl)phenoxy]propyl]benzamides are synthesized. The theoretical ly predicted in vitro activities of these compounds were found to be i n accordance with in vivo tests (percent of inhibition of gastric juic e and acid output [mEq/H+/3 h]).