Novel tetrahydroisoquinolines are histamine H3 antagonists and serotonin reuptake inhibitors.
A series of novel 4-aryl-1,2,3,4-tetrahydroisoquinoline-based histamine H(3) ligands that also have serotonin reuptake transporter inhibitor activity is described. The synthesis, in vitro biological data, and select pharmacokinetic data for these novel compounds are discussed.
Letavic
Michael A
MA
Johnson & Johnson Pharmaceutical Research and Development L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA. mletavic@prdus.jnj.com
Keith
John M
JM
Jablonowski
Jill A
JA
Stocking
Emily M
EM
Gomez
Leslie A
LA
Ly
Kiev S
KS
Miller
Jennifer M
JM
Barbier
Ann J
AJ
Bonaventure
Pascal
P
Boggs
Jamin D
JD
Wilson
Sandy J
SJ
Miller
Kirsten L
KL
Lord
Brian
B
McAllister
Heather M
HM
Tognarelli
D J
DJ
Wu
Jiejun
J
Abad
Marta C
MC
Schubert
Carsten
C
Lovenberg
Timothy W
TW
Carruthers
Nicholas I
NI
D000818:Animals; D018360:Crystallography, X-Ray; D050483:Dopamine Plasma Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism; D006207:Half-Life; D006633:Histamine Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D008958:Models, Molecular; D008968:Molecular Conformation; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D018100:Receptors, Histamine H3 / Q000187:drug effects*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*
D050483:Dopamine Plasma Membrane Transport Proteins; D006633:Histamine Antagonists; D007202:Indicators and Reagents; D009638:Norepinephrine; D018100:Receptors, Histamine H3; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D044005:Tetrahydroisoquinolines