title: Pyrrolidino-tetrahydroisoquinolines as potent dual H3 antagonist and serotonin transporter inhibitors.
abstract: A series of novel and potent pyrrolidino-tetrahydroisoquinolines with dual histamine H(3) antagonist/serotonin transporter inhibitor activity is described. A highly regio- and diastereoselective synthesis of the pyrrolidino-tetrahydroisoquinoline core involving acid mediated ring-closure of an acetophenone intermediate followed by reduction with NaCNBH(3) was developed. In vitro and in vivo data are discussed.
authors.affiliation: Johnson & Johnson Pharmaceutical Research and Development L.L.C., 3210 Merryfield Row, La Jolla, 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: Ronald L
authors.initials: RL
authors.lastname: Wolin
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: Curt
authors.initials: C
authors.lastname: Mazur
authors.forename: Ian C
authors.initials: IC
authors.lastname: Fraser
authors.forename: Brian
authors.initials: B
authors.lastname: Lord
authors.forename: Leah
authors.initials: L
authors.lastname: Aluisio
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Lovenberg
authors.forename: Nicholas I
authors.initials: NI
authors.lastname: Carruthers
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003863:Depression / Q000188:drug therapy; D015195:Drug Design; D006633:Histamine Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D008968:Molecular Conformation; D051381:Rats; D018100:Receptors, Histamine H3 / Q000737:chemistry*; D012701:Serotonin / Q000737:chemistry*; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D006633:Histamine Antagonists; D018100:Receptors, Histamine H3; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D044005:Tetrahydroisoquinolines