Potent dihydroquinolinone dopamine D2 partial agonist/serotonin reuptake inhibitors for the treatment of schizophrenia

Yinfa Yan; Ping Zhou; David P. Rotella; Rolf Feenstra; Chris G. Kruse; Jan Hendrik Reinders; Martina van der Neut; Margaret Lai; Jean Zhang; Dianne M. Kowal; Tikva Carrick; Karen L. Marquis; Mark H. Pausch; Albert J. Robichaud

doi:10.1016/j.bmcl.2010.02.105

Potent dihydroquinolinone dopamine D₂ partial agonist/serotonin reuptake inhibitors for the treatment of schizophrenia

Yinfa Yan
, Ping Zhou
, David P. Rotella
, Rolf Feenstra
, Chris G. Kruse
, Jan Hendrik Reinders
, Martina van der Neut
, Margaret Lai
, Jean Zhang
, Dianne M. Kowal
, Tikva Carrick
, Karen L. Marquis
, Mark H. Pausch
, Albert J. Robichaud

Chemistry and Biochemistry

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

21 Scopus citations

Abstract

A dihydroquinolinone moiety was found to be a potent serotonin reuptake inhibitor pharmacophore when combined with certain amines. This fragment was coupled with selected D₂ ligands to prepare a series of dual acting compounds with attractive in vitro profiles as dopamine D₂ partial agonists and serotonin reuptake inhibitors. Structure-activity studies revealed that the linker plays a key role in contributing to D₂ affinity, function, and SRI activity.

Original language	English
Pages (from-to)	2983-2986
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	20
Issue number	9
DOIs	https://doi.org/10.1016/j.bmcl.2010.02.105
State	Published - 1 May 2010

Keywords

Dopamine D partial agonist
Schizophrenia
Serotonin reuptake inhibitor

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10.1016/j.bmcl.2010.02.105

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Yan, Y., Zhou, P., Rotella, D. P., Feenstra, R., Kruse, C. G., Reinders, J. H., Neut, M. V. D., Lai, M., Zhang, J., Kowal, D. M., Carrick, T., Marquis, K. L., Pausch, M. H., & Robichaud, A. J. (2010). Potent dihydroquinolinone dopamine D₂ partial agonist/serotonin reuptake inhibitors for the treatment of schizophrenia. Bioorganic and Medicinal Chemistry Letters, 20(9), 2983-2986. https://doi.org/10.1016/j.bmcl.2010.02.105

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title = "Potent dihydroquinolinone dopamine D2 partial agonist/serotonin reuptake inhibitors for the treatment of schizophrenia",

abstract = "A dihydroquinolinone moiety was found to be a potent serotonin reuptake inhibitor pharmacophore when combined with certain amines. This fragment was coupled with selected D2 ligands to prepare a series of dual acting compounds with attractive in vitro profiles as dopamine D2 partial agonists and serotonin reuptake inhibitors. Structure-activity studies revealed that the linker plays a key role in contributing to D2 affinity, function, and SRI activity.",

keywords = "Dopamine D partial agonist, Schizophrenia, Serotonin reuptake inhibitor",

author = "Yinfa Yan and Ping Zhou and Rotella, \{David P.\} and Rolf Feenstra and Kruse, \{Chris G.\} and Reinders, \{Jan Hendrik\} and Neut, \{Martina van der\} and Margaret Lai and Jean Zhang and Kowal, \{Dianne M.\} and Tikva Carrick and Marquis, \{Karen L.\} and Pausch, \{Mark H.\} and Robichaud, \{Albert J.\}",

year = "2010",

month = may,

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doi = "10.1016/j.bmcl.2010.02.105",

language = "English",

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pages = "2983--2986",

journal = "Bioorganic and Medicinal Chemistry Letters",

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}

Yan, Y, Zhou, P, Rotella, DP, Feenstra, R, Kruse, CG, Reinders, JH, Neut, MVD, Lai, M, Zhang, J, Kowal, DM, Carrick, T, Marquis, KL, Pausch, MH & Robichaud, AJ 2010, 'Potent dihydroquinolinone dopamine D₂ partial agonist/serotonin reuptake inhibitors for the treatment of schizophrenia', Bioorganic and Medicinal Chemistry Letters, vol. 20, no. 9, pp. 2983-2986. https://doi.org/10.1016/j.bmcl.2010.02.105

TY - JOUR

T1 - Potent dihydroquinolinone dopamine D2 partial agonist/serotonin reuptake inhibitors for the treatment of schizophrenia

AU - Yan, Yinfa

AU - Zhou, Ping

AU - Rotella, David P.

AU - Feenstra, Rolf

AU - Kruse, Chris G.

AU - Reinders, Jan Hendrik

AU - Neut, Martina van der

AU - Lai, Margaret

AU - Zhang, Jean

AU - Kowal, Dianne M.

AU - Carrick, Tikva

AU - Marquis, Karen L.

AU - Pausch, Mark H.

AU - Robichaud, Albert J.

PY - 2010/5/1

Y1 - 2010/5/1

N2 - A dihydroquinolinone moiety was found to be a potent serotonin reuptake inhibitor pharmacophore when combined with certain amines. This fragment was coupled with selected D2 ligands to prepare a series of dual acting compounds with attractive in vitro profiles as dopamine D2 partial agonists and serotonin reuptake inhibitors. Structure-activity studies revealed that the linker plays a key role in contributing to D2 affinity, function, and SRI activity.

AB - A dihydroquinolinone moiety was found to be a potent serotonin reuptake inhibitor pharmacophore when combined with certain amines. This fragment was coupled with selected D2 ligands to prepare a series of dual acting compounds with attractive in vitro profiles as dopamine D2 partial agonists and serotonin reuptake inhibitors. Structure-activity studies revealed that the linker plays a key role in contributing to D2 affinity, function, and SRI activity.

KW - Dopamine D partial agonist

KW - Schizophrenia

KW - Serotonin reuptake inhibitor

UR - https://www.scopus.com/pages/publications/77950859625

U2 - 10.1016/j.bmcl.2010.02.105

DO - 10.1016/j.bmcl.2010.02.105

M3 - Article

C2 - 20347298

AN - SCOPUS:77950859625

SN - 0960-894X

VL - 20

SP - 2983

EP - 2986

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 9

ER -

Potent dihydroquinolinone dopamine D₂ partial agonist/serotonin reuptake inhibitors for the treatment of schizophrenia

Abstract

Keywords

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