Computer-automated structure evaluation of gastric antiulcer compounds: study of cytoprotective and antisecretory imidazo[1,2-a]pyridines and -pyrazines.

A quantitative structure-activity relationship study of a set of antiulcer compounds has been performed using the computer-automated structure evaluation methodology. Computer-automated structure evaluation identified cyanomethyl and hydroxymethyl functionalities, substituted in the 3-position of imidazo[1,2-a]pyridine and -Pyrazine, as descriptors relevant to antisecretory activity. The phenoxy group at the 8-position and the methyl group at the 2-position were shown to be sterically involved in the activity. A parabolic relationship was observed between the antisecretory activity and the logarithm of the partition coefficient of the compounds. Thus, hydrophobicity is found to be a necessary criterion for the inhibition of acid secretion. An attempt has been made to provide a rationale for designing a more potent antiulcer agent in this series of congeneric compounds.