On the structure-activity relationship of histamine H2-receptor antagonists based on the X-ray crystal structures and 1H-NMR spectra of amidine derivatives

T Ishida, Y In, M Shibata, M Doi, M Inoue and I Yanagisawa

The conformation of six amidine compounds, which possess a common 3-[(4- thiazolyl)methylthio]propionylamidine framework but exhibit different activities as histamine H2-receptor antagonists, have been subjected to both single crystal X-ray structural and 1H-NMR analyses. The X-ray studies suggest a correlation between antagonist activity and the relative spatial orientation of the thiazolyl and amidine nitrogen atoms. This correlation is supported by a comparison of the conformations observed for the amidines with those of other H2-receptor antagonists and reveal that a folded conformation, specifically the NH...N intramolecular hydrogen-bonded configuration, is important for antagonist activity. The 1H-NMR measurements on the active amidine compounds show that the intramolecular NH...N bond is likely to be present in solution.

Volume 31, Issue 4, pp. 410-416, 04/01/1987
Copyright © 1987 by American Society for Pharmacology and Experimental Therapeutics