51. Potent dihydroquinolinone dopamine D2 partial agonist/serotonin reuptake inhibitors for the treatment of schizophrenia
- Author
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Jean Zhang, Ping Zhou, Tikva Carrick, Albert J. Robichaud, Rolf Feenstra, Jan-Hendrik Reinders, Dianne Kowal, Chris G. Kruse, Martina A.W. van der Neut, Yinfa Yan, David P. Rotella, Mark H. Pausch, Margaret Lai, and Karen L. Marquis
- Subjects
Serotonin reuptake inhibitor ,Clinical Biochemistry ,Pharmaceutical Science ,Pharmacology ,Quinolones ,Biochemistry ,Partial agonist ,Reuptake ,Structure-Activity Relationship ,Dopamine receptor D2 ,Drug Discovery ,Moiety ,Animals ,Molecular Biology ,biology ,Chemistry ,Receptors, Dopamine D2 ,Organic Chemistry ,Disease Models, Animal ,Norepinephrine transporter ,Dopamine Agonists ,Receptor, Serotonin, 5-HT1A ,biology.protein ,Schizophrenia ,Molecular Medicine ,Pharmacophore ,Endogenous agonist ,Selective Serotonin Reuptake Inhibitors ,Antipsychotic Agents - Abstract
A dihydroquinolinone moiety was found to be a potent serotonin reuptake inhibitor pharmacophore when combined with certain amines. This fragment was coupled with selected D2 ligands to prepare a series of dual acting compounds with attractive in vitro profiles as dopamine D2 partial agonists and serotonin reuptake inhibitors. Structure–activity studies revealed that the linker plays a key role in contributing to D2 affinity, function, and SRI activity.
- Published
- 2010