Antiulcer agents. 3. Structure-activity-toxicity relationships of substituted imidazo[1,2-a]pyridines and a related imidazo[1,2-a]pyrazine.
Investigation of the interrelationship between structure, antiulcer activity, and toxicology screening data derived from a series of compounds selected from structure-activity studies directed toward identifying a successor to 3-(cyanomethyl)-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine, Sch 28080 (1), has identified 3-(cyanomethyl)-2,7-dimethyl-8-(phenylmethoxy)imidazo[1,2 -a]pyridine (5), 3-amino-2-methyl-8-(2-phenylethyl)imidazo[1,2-a]pyridine (6), and 3-amino-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyrazine (7). These analogues exhibit a combination of antisecretory and cytoprotective activity in animal models, while eliminating the adverse effects of the prototype 1. One of these, 3-amino-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyrazine, Sch 32651 (7), has a profile meeting all criteria.
Kaminski
J J
JJ
Pharmaceutical Research Division, Schering-Plough Corporation, Bloomfield, New Jersey 07003.
Perkins
D G
DG
Frantz
J D
JD
Solomon
D M
DM
Elliott
A J
AJ
Chiu
P J
PJ
Long
J F
JF
D000818:Animals; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D008297:Male; D051379:Mice; D011719:Pyrazines / Q000138:chemical synthesis / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D000897:Anti-Ulcer Agents; D007093:Imidazoles; D011719:Pyrazines; D011725:Pyridines