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

David 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. Navarra & 4 others Radka Graf, Julie Brennan, Karen L. Marquis, Mark H. Pausch

Research output: Contribution to journalArticleResearchpeer-review

14 Citations (Scopus)

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

Fingerprint

Serotonin Uptake Inhibitors
Dopamine
Schizophrenia
Dopamine D2 Receptors
Assays
Ligands
Molecules
Therapeutics

Keywords

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

Cite this

Rotella, David ; McFarlane, Geraldine R. ; Greenfield, Alexander ; Grosanu, Cristina ; Robichaud, Albert J. ; Denny, Rajiah Aldrin ; Feenstra, Rolf W. ; Núñez-García, Sara ; Reinders, Jan Hendrik ; Neut, Martina van der ; 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. / Tetrahydrocarbazole-based serotonin reuptake inhibitor/dopamine D2 partial agonists for the potential treatment of schizophrenia. In: Bioorganic and Medicinal Chemistry Letters. 2009 ; Vol. 19, No. 19. pp. 5552-5555.
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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.",
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Rotella, D, McFarlane, GR, Greenfield, A, Grosanu, C, Robichaud, AJ, Denny, RA, Feenstra, RW, Núñez-García, S, Reinders, JH, Neut, MVD, McCreary, A, Kruse, CG, Sullivan, K, Pruthi, F, Lai, M, Zhang, J, Kowal, DM, Carrick, T, Grauer, SM, Navarra, RL, Graf, R, Brennan, J, Marquis, KL & Pausch, MH 2009, 'Tetrahydrocarbazole-based serotonin reuptake inhibitor/dopamine D2 partial agonists for the potential treatment of schizophrenia', Bioorganic and Medicinal Chemistry Letters, vol. 19, no. 19, pp. 5552-5555. https://doi.org/10.1016/j.bmcl.2009.08.050

Tetrahydrocarbazole-based serotonin reuptake inhibitor/dopamine D2 partial agonists for the potential treatment of schizophrenia. / Rotella, David; McFarlane, Geraldine R.; Greenfield, Alexander; Grosanu, Cristina; Robichaud, Albert J.; Denny, Rajiah Aldrin; Feenstra, Rolf W.; Núñez-García, Sara; Reinders, Jan Hendrik; Neut, Martina van der; 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.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 19, No. 19, 01.10.2009, p. 5552-5555.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Tetrahydrocarbazole-based serotonin reuptake inhibitor/dopamine D2 partial agonists for the potential treatment of schizophrenia

AU - Rotella, David

AU - McFarlane, Geraldine R.

AU - Greenfield, Alexander

AU - Grosanu, Cristina

AU - Robichaud, Albert J.

AU - Denny, Rajiah Aldrin

AU - Feenstra, Rolf W.

AU - Núñez-García, Sara

AU - Reinders, Jan Hendrik

AU - Neut, Martina van der

AU - McCreary, Andrew

AU - Kruse, Chris G.

AU - Sullivan, Kelly

AU - Pruthi, Farhana

AU - Lai, Margaret

AU - Zhang, Jean

AU - Kowal, Dianne M.

AU - Carrick, Tikva

AU - Grauer, Steven M.

AU - Navarra, Rachel L.

AU - Graf, Radka

AU - Brennan, Julie

AU - Marquis, Karen L.

AU - Pausch, Mark H.

PY - 2009/10/1

Y1 - 2009/10/1

N2 - 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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KW - Dopamine D partial agonist

KW - Dual-acting molecule

KW - Schizophrenia

KW - SRI

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U2 - 10.1016/j.bmcl.2009.08.050

DO - 10.1016/j.bmcl.2009.08.050

M3 - Article

VL - 19

SP - 5552

EP - 5555

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 19

ER -