Tetrahydrocarbazole-based serotonin reuptake inhibitor/dopamine D2 partial agonists for the potential treatment of schizophrenia

A 5-fluoro-tetrahydrocarbazole serotonin reuptake inhibitor (SRI) building block was combined with a variety of linkers and dopamine D2 receptor ligands in an attempt to identify potent D2 partial agonist/SRI molecules for treatment of schizophrenia. This approach has the potential to treat a broade...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2009-10, Vol.19 (19), p.5552-5555
Main Authors: ROTELLA, David P, MCFARLANE, Geraldine R, MCCREARY, Andrew, KRUSE, Chris G, SULLIVAN, Kelly, PRUTHI, Farhana, LAI, Margaret, ZHANG, Jean, KOWAL, Dianne M, CARRICK, Tikva, GRAUER, Steven M, NAVARRA, Rachel L, GREENFIELD, Alexander, GRAF, Radka, BRENNAN, Julie, MARQUIS, Karen L, PAUSCH, Mark H, GROSANU, Cristina, ROBICHAUD, Albert J, DENNY, Rajiah Aldrin, FEENSTRA, Rolf W, NUNEZ-GARCIA, Sara, REINDERS, Jan-Hendrik, VAN DER NEUT, Martina
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Carbazoles - chemical synthesis
Carbazoles - chemistry
Carbazoles - pharmacology
Catecholaminergic system
Disease Models, Animal
Dopamine Agonists - chemical synthesis
Dopamine Agonists - chemistry
Dopamine Agonists - pharmacology
Medical sciences
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Pharmacology. Drug treatments
Psycholeptics: tranquillizer, neuroleptic
Psychology. Psychoanalysis. Psychiatry
Psychopharmacology
Rats
Receptor, Serotonin, 5-HT1A - metabolism
Receptors, Dopamine D2 - agonists
Receptors, Dopamine D2 - metabolism
Schizophrenia - drug therapy
Serotonin 5-HT1 Receptor Antagonists
Serotonin Uptake Inhibitors - chemical synthesis
Serotonin Uptake Inhibitors - chemistry
Serotonin Uptake Inhibitors - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A 5-fluoro-tetrahydrocarbazole serotonin reuptake inhibitor (SRI) building block was combined with a variety of linkers and dopamine D2 receptor ligands in an attempt to identify potent D2 partial agonist/SRI molecules for treatment of schizophrenia. This approach has the potential to treat a broader range of symptoms compared to existing therapies. Selected compounds in this series demonstrate high affinity for both targets and D2 partial agonism in cell-based and in vivo assays.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2009.08.050