[Theoretical conformation study of tiotidine and nizatidine, two strong histamine H2-receptor antagonists]

A conformational study of two potent histamine H2-receptor antagonists, tiotidine and nizatidine, have been made. The geometry of cyanoguanidine and guanidinothiazol in tiotidine and diaminonitroetane in nizatidine was obtained using MNDO calculations. On the other hand, the conformations of the molecules, under study were obtained using a empirical atom-atom potential that stimulates the drug behavior in aqueous solution at 37 degrees C. For both molecules, folded and very rigid conformations, with a substantial parallelism between the planes of the rings and the polar groups, were obtained. All the possibilities of the configurational isomerism on the polar groups of this molecules was taken into account. The results obtained show that the polar group can adopt just staggered forms (Z,E and E,Z). These results agree with experimental and theoretical studies made on the polar group. The type of conformations found in tiotidine and nizatidine are very similar to those previously found for metiamide, cimetidine, ranitidine and etintidine. These results would permit us to propose that these conformations play a determinant role in the histamine H2-receptor recognition.