ENRIZENRIZ] ricardoricardo] danieldaniel]
Theoretical study of selective H3 receptor antagonists of histamine
R D ENRIZENRIZ]; M.R.ESTRADA; E.A.JAUREGUI; C.A.PONCE; F. TOMAS VERT
JOURNAL OF MOLECULAR STRUCTURE THEOCHEM
ELSEVIER SCIENCE BV
Lugar: Amsterdam; Año: 1993 vol. 280 p. 5 - 5
The conformations and charge distributions of three selective H3 receptor antagonists of histamine weredetermined using the MNDO approach. The results suggest that the confo~ation~ flexibi~ties of betahistine,~~-(2-phenylacetyl)~stamine and thioperamide are different; however, the low-energy confo~ations of thesecompounds show closely related spatial orderings. The MNDO calculations predict a significant population of theNlH form in the imidazole systems of Na-(2-phenylacetyl)histamine and thioperamide. Our results indicate thatthe conformational behaviour of H3 antagonists is closely similar to that reported for H2 antagonists of histamine.These results emphasize the importance of tautomeric and electronic effects rather than conformational factorsin accounting for the different antagonist activity at H2 or H3 receptors of several H2 ligands.