Estudio Teórico conformacional de la famotidina

ENRIZ R D; E.A.JAUREGUI

Journal of the Argentine Chemical Society

ASOCIACIÓN QUÍMICA ARGENTINA

Lugar: Buenos Aires; Año: 1990 vol. 78 p. 135 - 146

0365-0375

SUMMARY: A conformational study of famatidine, a highly selectiveHz -histamine antagonist was carried out using MNDO and molecularmechanics calculations. A full MNDO-opümization of the geometricalparameters of guanidinothyazole and sulfonamido-amidine groupswas carried out. MNDO study gives a planar spatial ordering forguanidinothyazole group. Sulfonamido-amidine group contrast/ markedly with other polar groups of Hz -receptor histamine antagonists,since MNDO study showed no configurational isomerism for this group.The conformational study showed that famotidine is a very flexiblemolecule, which can adopt different conformations. Howeuer foldedand half-folded conformations appears to be important in the dru,receptorinteraction. The possible alternative attack site of guanidinosubstituent of guanidinothyazole, the conformational behavior ofsulfanomida-amidine group and the molecular flexibility of methylthioethylflexible said chain, could be significative structuralcharacteristícs for the interaction between famotidine wíth the histamineHz-receptor.