Tetrahydrocarbazole-based serotonin reuptake inhibitor/dopamine D sub(2) partial agonists for the potential treatment of schizophrenia

• Published in: Bioorganic & medicinal chemistry letters Vol. 19; no. 19; pp. 5552 - 5555
• Main Authors: Rotella, David P, McFarlane, Geraldine R, Greenfield, Alexander, Grosanu, Cristina, Robichaud, Albert J, Denny, Rajiah Aldrin, Feenstra, Rolf W, Nunez-Garcia, Sara, Reinders, Jan-Hendrik, Van der Neut, Martina, McCreary, Andrew, Kruse, Chris G, Sullivan, Kelly, Pruthi, Farhana, Lai, Margaret, Zhang, Jean, Kowal, Dianne M, Carrick, Tikva, Grauer, Steven M, Navarra, Rachel L, Graf, Radka, Brennan, Julie, Marquis, Karen L, Pausch, Mark H
• Format: Journal Article
• Language: English
• Published: 01.10.2009
• ISSN: 0960-894X
• DOI: 10.1016/j.bmcl.2009.08.050

A 5-fluoro-tetrahydrocarbazole serotonin reuptake inhibitor (SRI) building block was combined with a variety of linkers and dopamine D sub(2) receptor ligands in an attempt to identify potent D sub(2) 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 D sub(2) partial agonism in cell-based and in vivo assays.