Study of the configurational isomerism of polar groups present in histamine H2 receptor antagonists

R D ENRIZ; E.A.JAUREGUI

JOURNAL OF MOLECULAR STRUCTURE THEOCHEM

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 1990 vol. 207 p. 269 - 283

0166-1280

MNDO AM1 and SCF-MO techniques were applied to methylated derivatives of the thioureagroup of metiamide, the cyanoguanidine group of cimetidine, the diamino-nitroethene group ofranitidine, the propargyl-cyanoguanidine group of etintidine and the sulfonamido-amidine groupof famotidine. The calculated preferred configurations agree with those indicated from previousexperimental (NMR and X-ray) studies, and with previous molecular-mechanics calculationsinvolving corresponding HS-antagonists, which indicates a determinant role of the groups on theconformations of the antagonists. The highest activity in the antagonists is associated with groupshaving the fewest configurational possibilities, suggesting that the latter leads to the highest specificityin HZ-receptor recognition.