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. Navarra

Radka 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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10.1016/j.bmcl.2009.08.050

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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

@article{a65c6b3e4a12410289db0b2f00f933aa,

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,

day = "1",

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

language = "English",

volume = "19",

pages = "5552--5555",

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

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.

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

UR - https://www.scopus.com/pages/publications/69949086742

U2 - 10.1016/j.bmcl.2009.08.050

DO - 10.1016/j.bmcl.2009.08.050

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AN - SCOPUS:69949086742

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JO - Bioorganic and Medicinal Chemistry Letters

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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