title: Irreversible H2-antagonism of the four isomeric butyl analogues of mifentidine.
abstract: 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.
authors.affiliation: Department of Pharmacochemistry, Faculty of Chemistry, Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: H M
authors.initials: HM
authors.lastname: Bastiaans
authors.forename: A
authors.initials: A
authors.lastname: Donetti
authors.forename: K
authors.initials: K
authors.lastname: Kramer
authors.forename: G
authors.initials: G
authors.lastname: Bietti
authors.forename: E
authors.initials: E
authors.lastname: Cereda
authors.forename: D
authors.initials: D
authors.lastname: Dubini
authors.forename: M
authors.initials: M
authors.lastname: Mondini
authors.forename: A
authors.initials: A
authors.lastname: Bast
authors.forename: H
authors.initials: H
authors.lastname: Timmerman
mesh_terms: 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
chemical_list: D006635:Histamine H2 Antagonists; D007093:Imidazoles; C039796:mifentidine