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Tetrahydrocarbazole-based serotonin reuptake inhibitor/dopamine D2 partial agonists for the potential treatment of schizophrenia. 2009
David P Rotella, and
Geraldine R McFarlane, and
Alexander Greenfield, and
Cristina Grosanu, and
Albert J Robichaud, and
Rajiah Aldrin Denny, and
Rolf W Feenstra, and
Sara Núñez-García, and
Jan-Hendrik Reinders, and
Martina van der Neut, and
Andrew McCreary, and
Chris G Kruse, and
Kelly Sullivan, and
Farhana Pruthi, and
Margaret Lai, and
Jean Zhang, and
Dianne M Kowal, and
Tikva Carrick, and
Steven M Grauer, and
Rachel L Navarra, and
Radka Graf, and
Julie Brennan, and
Karen L Marquis, and
Mark H Pausch
Chemical Sciences, Wyeth Research, CN 8000 Princeton, NJ 08543, United States. rotelld@wyeth.com
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.
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