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

David P. Rotella, Geraldine R. McFarlane, Alexander Greenfield, Cristina Grosanu, Albert J. Robichaud, Rajiah Aldrin Denny, Rolf W. Feenstra, Sara Núñez-García, Jan Hendrik Reinders, Martina van der Neut, Andrew McCreary, Chris G. Kruse, Kelly Sullivan, Farhana Pruthi, Margaret Lai, Jean Zhang, Dianne M. Kowal, Tikva Carrick, Steven M. Grauer, Rachel L. NavarraRadka Graf, Julie Brennan, Karen L. Marquis, Mark H. Pausch

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Abstract

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.

Original languageEnglish
Pages (from-to)5552-5555
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume19
Issue number19
DOIs
StatePublished - 1 Oct 2009

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Keywords

  • Dopamine D partial agonist
  • Dual-acting molecule
  • SRI
  • Schizophrenia

Cite this

Rotella, D. P., McFarlane, G. R., Greenfield, A., Grosanu, C., Robichaud, A. J., Denny, R. A., Feenstra, R. W., Núñez-García, S., Reinders, J. H., Neut, M. V. D., McCreary, A., Kruse, C. G., Sullivan, K., Pruthi, F., Lai, M., Zhang, J., Kowal, D. M., Carrick, T., Grauer, S. M., ... Pausch, M. H. (2009). Tetrahydrocarbazole-based serotonin reuptake inhibitor/dopamine D2 partial agonists for the potential treatment of schizophrenia. Bioorganic and Medicinal Chemistry Letters, 19(19), 5552-5555. https://doi.org/10.1016/j.bmcl.2009.08.050