Estudio teorico conformacional de tiotidina y nizatidina

ENRIZ R D; E.A.JAUREGUI

ACTA CIENTIFICA VENEZOLANA

Asociación Venezolana para el Avance de la Ciencia

Lugar: Caracas; Año: 1991 vol. 42 p. 70 - 76

0001-5504

A conformational study of two potent histamine H2-receptor antagonists, ' tiotidine and nizatidine, have been made.The geometry of cyanoguanidine and guanidinolhiazol in tiotidine and diaminonitro,ctane in nizatidine was obtained using MNDOcalculations. On the other hand, the conformations of the molecules, under study were obtained using a empirical atom-atompotential that simulates the drug behavior in aqueous solution at 37 ºC. Por both molecules, folded and vcry rigid conformations,with a substantial parallelism between the planes of the rings and the polar groups, were obtained. All the possibilities of theconfigurational isomerism on the polar groups of this molecules was takcn into account. The results obtained show that the polargroup can adopt just staggered forms (Z,E and E,Z). These results agree with experimentals and theoretical studies made on the polargroup. 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 inthe histamine H2-receptor recognition. Key words: conformation, tiotidine, nizatidinc, H2-receptors, histamine, antagonism.