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.
Klopman
G
G
Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106.
Srivastava
S
S
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D003451:Cryoprotective Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D001330:Electronic Data Processing; D007093:Imidazoles / Q000494:pharmacology*; D010437:Peptic Ulcer / Q000188:drug therapy*; D011724:Pyridazines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D012636:Secretory Rate / Q000187:drug effects; D013329:Structure-Activity Relationship
D000897:Anti-Ulcer Agents; D003451:Cryoprotective Agents; D007093:Imidazoles; D011724:Pyridazines; D011725:Pyridines