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. Navarra; Radka Graf; Julie Brennan; Karen L. Marquis; Mark H. Pausch

doi:10.1016/j.bmcl.2009.08.050

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

Chemistry and Biochemistry

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

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 language	English
Pages (from-to)	5552-5555
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	19
Issue number	19
DOIs	https://doi.org/10.1016/j.bmcl.2009.08.050
State	Published - 1 Oct 2009

Keywords

Dopamine D partial agonist
Dual-acting molecule
SRI
Schizophrenia

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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

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

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.",

keywords = "Dopamine D partial agonist, Dual-acting molecule, SRI, Schizophrenia",

author = "Rotella, {David P.} and McFarlane, {Geraldine R.} and Alexander Greenfield and Cristina Grosanu and Robichaud, {Albert J.} and Denny, {Rajiah Aldrin} and Feenstra, {Rolf W.} and Sara N{\'u}{\~n}ez-Garc{\'i}a and Reinders, {Jan Hendrik} and Neut, {Martina van der} and Andrew McCreary and Kruse, {Chris G.} and Kelly Sullivan and Farhana Pruthi and Margaret Lai and Jean Zhang and Kowal, {Dianne M.} and Tikva Carrick and Grauer, {Steven M.} and Navarra, {Rachel L.} and Radka Graf and Julie Brennan and Marquis, {Karen L.} and Pausch, {Mark H.}",

year = "2009",

month = oct,

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doi = "10.1016/j.bmcl.2009.08.050",

language = "English",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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Rotella, DP, 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

TY - JOUR

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

AU - Rotella, David P.

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

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AB - 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.

KW - Dopamine D partial agonist

KW - Dual-acting molecule

KW - SRI

KW - Schizophrenia

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JF - Bioorganic and Medicinal Chemistry Letters

IS - 19

ER -

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

Abstract

Keywords

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