title: A new class of diamine-based human histamine H3 receptor antagonists: 4-(aminoalkoxy)benzylamines.
abstract: 4-(Aminoalkoxy)benzylamines were prepared and screened for in vitro activity at the human histamine H(3) receptor. Some members of this series exhibited subnanomolar binding affinities. Analogues in which one nitrogen atom was replaced with a methine group showed greatly reduced binding affinities. Six members of this series were found to be antagonists in a cell-based model of human histamine H(3) receptor activation. One member of this series, 1-[4-(3-piperidin-1-ylpropoxy)benzyl]piperidine (7b), was found to be a selective and potent human H(3) receptor antagonist.
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C., 3210 Merryfield Row, San Diego, California 92121, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Apodaca
authors.forename: Curt A
authors.initials: CA
authors.lastname: Dvorak
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
authors.forename: Ann J
authors.initials: AJ
authors.lastname: Barbier
authors.forename: Jamin D
authors.initials: JD
authors.lastname: Boggs
authors.forename: Sandy J
authors.initials: SJ
authors.lastname: Wilson
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Lovenberg
authors.forename: Nicholas I
authors.initials: NI
authors.lastname: Carruthers
mesh_terms: D000818:Animals; D001596:Benzylamines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D018938:Caco-2 Cells; D002460:Cell Line; D002540:Cerebral Cortex / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D006633:Histamine Antagonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D010539:Permeability; D010880:Piperidines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D018100:Receptors, Histamine H3 / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C477200:1-(4-(3-piperidin-1-ylpropoxy)benzyl)piperidine; D001596:Benzylamines; D006633:Histamine Antagonists; D010880:Piperidines; D018100:Receptors, Histamine H3; D000242:Cyclic AMP