title: Dual serotonin transporter inhibitor/histamine H3 antagonists: development of rigidified H3 pharmacophores.
abstract: A series of tetrahydroisoquinolines acting as dual serotonin transporter inhibitor/histamine H(3) antagonists is described. The introduction of polar aromatic spacers as part of the histamine H(3) pharmacophore was explored. A convergent synthesis of the final products allowing late stage introduction of the aromatic side chain was developed. In vitro and in vivo data are discussed.
authors.affiliation: Johnson & Johnson Pharmaceutical Research and Development L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA. jkeith@prdus.jnj.com
authors.forename: John M
authors.initials: JM
authors.lastname: Keith
authors.forename: Ann J
authors.initials: AJ
authors.lastname: Barbier
authors.forename: Sandy J
authors.initials: SJ
authors.lastname: Wilson
authors.forename: Kirstin
authors.initials: K
authors.lastname: Miller
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; D001921:Brain / Q000378:metabolism; D015195:Drug Design; D006633:Histamine Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D051381:Rats; D018100:Receptors, Histamine H3 / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects*; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D006633:Histamine Antagonists; D007202:Indicators and Reagents; D018100:Receptors, Histamine H3; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D044005:Tetrahydroisoquinolines; D006916:5-Hydroxytryptophan