Pyrrolidino-tetrahydroisoquinolines bearing pendant heterocycles as potent dual H3 antagonist and serotonin transporter inhibitors.
A series of novel and potent 6-heteroaryl-pyrrolidino-tetrahydroisoquinolines with dual histamine H(3) antagonist/serotonin transporter inhibitor activity is described. In vitro and in vivo data are discussed.
Keith
John M
JM
Johnson & Johnson Pharmaceutical Research & Development L.L.C., 3210 Merryfield Row, La Jolla, CA 92121, USA. jkeith@prdus.jnj.com
Gomez
Leslie A
LA
Barbier
Ann J
AJ
Wilson
Sandy J
SJ
Boggs
Jamin D
JD
Lord
Brian
B
Mazur
Curt
C
Aluisio
Leah
L
Lovenberg
Timothy W
TW
Carruthers
Nicholas I
NI
D000818:Animals; D001812:Blood-Brain Barrier; D006634:Histamine H1 Antagonists / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D011759:Pyrrolidines / Q000737:chemistry / Q000494:pharmacology*; D018100:Receptors, Histamine H3 / Q000187:drug effects*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects*; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines / Q000737:chemistry / Q000494:pharmacology*
D006634:Histamine H1 Antagonists; D011759:Pyrrolidines; D018100:Receptors, Histamine H3; D050486:Serotonin Plasma Membrane Transport Proteins; D044005:Tetrahydroisoquinolines