title: Dibasic non-imidazole histamine H3 receptor antagonists with a rigid biphenyl scaffold.
abstract: A class of rigid, dibasic, non-imidazole H3 antagonists was developed, starting from a series of previously described flexible compounds. The original polymethylene chain between two tertiary amine groups was replaced by a rigid scaffold, composed by a phenyl ring or a biphenyl fragment. Modulation of the distance between the two amine groups, and of their alkyl substituents, was driven by superposition of molecular models and docking into a receptor model, resulting in the identification of 1,1'-[biphenyl-4,4'-diylbis(methylene)]bis-piperidine (5) as a subtype-selective H3 antagonist with high binding affinity (pKi=9.47) at human H3 histamine receptor.
authors.affiliation: Dipartimento Farmaceutico, Università degli Studi di Parma, V. le G.P. Usberti 27/A, I-43100 Parma, Italy. giovanni.morini@unipr.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Morini
authors.forename: Mara
authors.initials: M
authors.lastname: Comini
authors.forename: Mirko
authors.initials: M
authors.lastname: Rivara
authors.forename: Silvia
authors.initials: S
authors.lastname: Rivara
authors.forename: Simone
authors.initials: S
authors.lastname: Lorenzi
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Bordi
authors.forename: Marco
authors.initials: M
authors.lastname: Mor
authors.forename: Lisa
authors.initials: L
authors.lastname: Flammini
authors.forename: Simona
authors.initials: S
authors.lastname: Bertoni
authors.forename: Vigilio
authors.initials: V
authors.lastname: Ballabeni
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Barocelli
authors.forename: Pier Vincenzo
authors.initials: PV
authors.lastname: Plazzi
mesh_terms: D000818:Animals; D002460:Cell Line; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008958:Models, Molecular; D051381:Rats; D018100:Receptors, Histamine H3 / Q000187:drug effects*
chemical_list: D006633:Histamine Antagonists; D007093:Imidazoles; D018100:Receptors, Histamine H3