Molecular conformations of aminophenylimidazoles exhibiting antiulcer activities.
To experimentally clarify a possible stereostructure-activity relationship proposed for H2-receptor antagonists, three 5-aminophenylimidazoles (1, 2 and 3), in which respective amino groups are located on the ortho, meta and para positions of the benzene ring, were synthesized and examined for their conformational characteristics using X-ray diffraction and proton nuclear magnetic resonance (1H-NMR) methods, and for antiulcer activities on rats and H2-receptor antagonist activities in guinea pig. The ortho isomer 1, which preferentially formed an intramolecular N-H (amino)...N (imidazole) hydrogen bond, showed the highest antiulcer activity with half the efficacy of cimetidine. On the other hand, none of 1, 2 and 3 showed significant H2-receptor antagonist activity. Based on these results, the conformational characteristic for the exhibition of antiulcer activity has been discussed.
Ishida
T
T
Osaka University of Pharmaceutical Sciences, Japan.
In
Y
Y
Inoue
M
M
Kurihara
T
T
Moriomoto
K
K
Morisaka
K
K
Shibata
K
K
D000814:Aniline Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008968:Molecular Conformation; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000188:drug therapy; D014961:X-Ray Diffraction
D000814:Aniline Compounds; D000897:Anti-Ulcer Agents; D007093:Imidazoles