Design, synthesis, and evaluation of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamides as selective dopamine D3 receptor ligands

Peng Jen Chen; Michelle Taylor; Suzy A. Griffin; Armaghan Amani; Hamed Hayatshahi; Kenneth Korzekwa; Min Ye; Robert H. Mach; Jin Liu; Robert R. Luedtke; John C. Gordon; Benjamin E. Blass

doi:10.1016/j.bmcl.2019.07.020

Design, synthesis, and evaluation of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamides as selective dopamine D₃ receptor ligands

Peng Jen Chen, Michelle Taylor, Suzy A. Griffin, Armaghan Amani, Hamed Hayatshahi, Kenneth Korzekwa, Min Ye, Robert H. Mach, Jin Liu, Robert R. Luedtke, John C. Gordon, Benjamin E. Blass

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Abstract

As part of our on-going effort to explore the role of dopamine receptors in drug addiction and identify potential novel therapies for this condition, we have a identified a series of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide D₃ ligands. Members of this class are highly selective for D₃ versus D₂, and we have identified two compounds (13g and 13r) whose rat in vivo IV pharmacokinetic properties that indicate that they are suitable for assessment in in vivo efficacy models of substance use disorders.

Original language	English
Pages (from-to)	2690-2694
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	29
Issue number	18
DOIs	https://doi.org/10.1016/j.bmcl.2019.07.020
State	Published - 15 Sep 2019

Keywords

D
D
Dopamine receptor
Drug addiction
G-protein coupled receptor (GPCR)

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Chen, P. J., Taylor, M., Griffin, S. A., Amani, A., Hayatshahi, H., Korzekwa, K., Ye, M., Mach, R. H., Liu, J., Luedtke, R. R., Gordon, J. C., & Blass, B. E. (2019). Design, synthesis, and evaluation of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamides as selective dopamine D₃ receptor ligands. Bioorganic and Medicinal Chemistry Letters, 29(18), 2690-2694. https://doi.org/10.1016/j.bmcl.2019.07.020

@article{8e4f357981184770b30c687306fb8b69,

title = "Design, synthesis, and evaluation of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamides as selective dopamine D3 receptor ligands",

abstract = "As part of our on-going effort to explore the role of dopamine receptors in drug addiction and identify potential novel therapies for this condition, we have a identified a series of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide D3 ligands. Members of this class are highly selective for D3 versus D2, and we have identified two compounds (13g and 13r) whose rat in vivo IV pharmacokinetic properties that indicate that they are suitable for assessment in in vivo efficacy models of substance use disorders.",

keywords = "D, D, Dopamine receptor, Drug addiction, G-protein coupled receptor (GPCR)",

author = "Chen, {Peng Jen} and Michelle Taylor and Griffin, {Suzy A.} and Armaghan Amani and Hamed Hayatshahi and Kenneth Korzekwa and Min Ye and Mach, {Robert H.} and Jin Liu and Luedtke, {Robert R.} and Gordon, {John C.} and Blass, {Benjamin E.}",

note = "Funding Information: The research reported in this publication was supported by the National Institute on Drug Abuse ( NIDA )/National Institutes of Health ( NIH ) under award numbers DA029840-06A1 and DA023957 . K i determinations for compound binding to receptors outside of the dopamine family were generously provided by the National Institute of Mental Health{\textquoteright}s Psychoactive Drug Screening Program, Contract # HHSN-271-2013-00017-C (NIMH PDSP). The NIMH PDSP is directed by Bryan L. Roth at the University of North Carolina at Chapel Hill and Project Officer Jamie Driscoll at NIMH, Bethesda MD, USA. For experimental details please refer to the PDSP web site https://pdsp.unc.edu/ims/investigator/web/ . The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",

year = "2019",

month = sep,

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doi = "10.1016/j.bmcl.2019.07.020",

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Chen, PJ, Taylor, M, Griffin, SA, Amani, A, Hayatshahi, H, Korzekwa, K, Ye, M, Mach, RH, Liu, J , Luedtke, RR, Gordon, JC & Blass, BE 2019, 'Design, synthesis, and evaluation of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamides as selective dopamine D₃ receptor ligands', Bioorganic and Medicinal Chemistry Letters, vol. 29, no. 18, pp. 2690-2694. https://doi.org/10.1016/j.bmcl.2019.07.020

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T1 - Design, synthesis, and evaluation of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamides as selective dopamine D3 receptor ligands

AU - Chen, Peng Jen

AU - Taylor, Michelle

AU - Griffin, Suzy A.

AU - Amani, Armaghan

AU - Hayatshahi, Hamed

AU - Korzekwa, Kenneth

AU - Ye, Min

AU - Mach, Robert H.

AU - Liu, Jin

AU - Luedtke, Robert R.

AU - Gordon, John C.

AU - Blass, Benjamin E.

N1 - Funding Information: The research reported in this publication was supported by the National Institute on Drug Abuse ( NIDA )/National Institutes of Health ( NIH ) under award numbers DA029840-06A1 and DA023957 . K i determinations for compound binding to receptors outside of the dopamine family were generously provided by the National Institute of Mental Health’s Psychoactive Drug Screening Program, Contract # HHSN-271-2013-00017-C (NIMH PDSP). The NIMH PDSP is directed by Bryan L. Roth at the University of North Carolina at Chapel Hill and Project Officer Jamie Driscoll at NIMH, Bethesda MD, USA. For experimental details please refer to the PDSP web site https://pdsp.unc.edu/ims/investigator/web/ . The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: © 2019 Elsevier Ltd

PY - 2019/9/15

Y1 - 2019/9/15

N2 - As part of our on-going effort to explore the role of dopamine receptors in drug addiction and identify potential novel therapies for this condition, we have a identified a series of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide D3 ligands. Members of this class are highly selective for D3 versus D2, and we have identified two compounds (13g and 13r) whose rat in vivo IV pharmacokinetic properties that indicate that they are suitable for assessment in in vivo efficacy models of substance use disorders.

AB - As part of our on-going effort to explore the role of dopamine receptors in drug addiction and identify potential novel therapies for this condition, we have a identified a series of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide D3 ligands. Members of this class are highly selective for D3 versus D2, and we have identified two compounds (13g and 13r) whose rat in vivo IV pharmacokinetic properties that indicate that they are suitable for assessment in in vivo efficacy models of substance use disorders.

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KW - Dopamine receptor

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M3 - Article

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AN - SCOPUS:85071060192

SN - 0960-894X

VL - 29

SP - 2690

EP - 2694

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 18

ER -

Design, synthesis, and evaluation of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamides as selective dopamine D₃ receptor ligands

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