A theoretical model for the histamine H2 receptor

ENRIZ R D; E.A.JAUREGUI

Drug design and delivery

New York : Harwood Academic, c1986-c1991

Lugar: New York; Año: 1991 vol. 7 p. 183 - 202

0884-2884

We describe an electronic and conformational study ofhistamine Hz-receptor ligands ofthe imidazole series,in which the possibilities of configurational isomerism (the thiourea group) and N3H and NlH tautomerism(imidazole ring) were considered. The results suggest that the conformational flexibility ofthe molecules andthe properties of the imidazole ring are of special importance in the display of Hz-receptor activity. Atheoretical model ofhistamine Hz-receptor interactions is proposed on the basis ofthese and other results. Avery importan! characteristic of our model is its ability to explain Hz-receptor activation by compoundswhich differ structurally, and to explain antagonism at the same receptor. The stereospecificty of rigidanalogues of cimetidine and tiotidine, and the importance of chain length in flexible histamineHz-antagonists are also accounted for.