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",

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

language = "English",

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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

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U2 - 10.1016/j.bmcl.2010.02.105

DO - 10.1016/j.bmcl.2010.02.105

M3 - Article

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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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