title: Dual serotonin transporter/histamine H3 ligands: Optimization of the H3 pharmacophore.
abstract: A series of tetrahydroisoquinolines acting as dual histamine H3/serotonin transporter ligands is described. A highly regio-selective synthesis of the tetrahydroisoquinoline core involving acid mediated ring-closure of an acetophenone intermediate followed by reduction with NaCNBH3 was developed. In vitro and in vivo data are discussed.
authors.affiliation: Johnson & Johnson Pharmaceutical Research and Development LLC, 3210 Merryfield Row, San Diego, CA 92121, USA. jkeith@prdus.jnj.com
authors.forename: John M
authors.initials: JM
authors.lastname: Keith
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Gomez
authors.forename: Michael A
authors.initials: MA
authors.lastname: Letavic
authors.forename: Kiev S
authors.initials: KS
authors.lastname: Ly
authors.forename: Jill A
authors.initials: JA
authors.lastname: Jablonowski
authors.forename: Mark
authors.initials: M
authors.lastname: Seierstad
authors.forename: Ann J
authors.initials: AJ
authors.lastname: Barbier
authors.forename: Sandy J
authors.initials: SJ
authors.lastname: Wilson
authors.forename: Jamin D
authors.initials: JD
authors.lastname: Boggs
authors.forename: Ian C
authors.initials: IC
authors.lastname: Fraser
authors.forename: Curt
authors.initials: C
authors.lastname: Mazur
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Lovenberg
authors.forename: Nicholas I
authors.initials: NI
authors.lastname: Carruthers
mesh_terms: D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis / Q000494:pharmacology; D008024:Ligands; D051379:Mice; D010879:Piperazines / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D018100:Receptors, Histamine H3 / Q000737:chemistry* / Q000187:drug effects*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D007546:Isoquinolines; D008024:Ligands; D010879:Piperazines; D018100:Receptors, Histamine H3; D050486:Serotonin Plasma Membrane Transport Proteins; D006916:5-Hydroxytryptophan