Irreversible H2-antagonism of the four isomeric butyl analogues of mifentidine.
It has been hypothesized that bidentate hydrogen bonding plays an important role in the interaction of imidazolylphenylformamidines with the H2-receptor. The present study, in which the degree of pseudo-irreversible H2-antagonism of the four isomeric butyl substituted mifentidine analogues was determined on the spontaneously beating right atrium of the male guinea-pig, lends further support to this hypothesis. In solution the EE/EZ ratio is different for the four isomeric butylated mifentidine analogues. The rank order of the percentage of E,E conformation, which favors a bidentate interaction, of the formamidine moiety parallels the rank order of pseudo-irreversible H2-antagonism.
Bastiaans
H M
HM
Department of Pharmacochemistry, Faculty of Chemistry, Vrije Universiteit, Amsterdam, The Netherlands.
Donetti
A
A
Kramer
K
K
Bietti
G
G
Cereda
E
E
Dubini
D
D
Mondini
M
M
Bast
A
A
Timmerman
H
H
D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008968:Molecular Conformation
D006635:Histamine H2 Antagonists; D007093:Imidazoles; C039796:mifentidine