Structure-activity relationship studies of highly selective inhibitors of the dopamine transporter: N-benzylpiperidine analogues of 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl) piperazine

Elisabeth Greiner; Thomas Prisinzano; Edward M. Johnson; Christina M. Dersch; Jamila Marcus; John S. Partilla; Richard B. Rothman; Arthur E. Jacobson; Kenner C. Rice

doi:10.1021/jm020419v

Structure-activity relationship studies of highly selective inhibitors of the dopamine transporter: N-benzylpiperidine analogues of 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl) piperazine

Elisabeth Greiner, Thomas Prisinzano, Edward M. Johnson, Christina M. Dersch, Jamila Marcus, John S. Partilla, Richard B. Rothman, Arthur E. Jacobson, Kenner C. Rice

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

19 Scopus citations

Abstract

A series of 4-[2-[bis(4-fluorophenyl)methoxy]ethyl-1-benzylpiperidines were examined for their ability to bind to the dopamine transporter (DAT), the serotonin transporter (SERT), and the norepinephrine transporter (NET). Binding results indicated that the presence of an electronwithdrawing group in the C₄-position of the N-benzyl group is beneficial for binding to the DAT. Several analogues have been identified with high affinity for the DAT, up to 500-fold selectivity over the SERT and about 170-fold selectivity over the NET in binding and uptake inhibition assays.

Original language	English
Pages (from-to)	1465-1469
Number of pages	5
Journal	Journal of Medicinal Chemistry
Volume	46
Issue number	8
DOIs	https://doi.org/10.1021/jm020419v
State	Published - Apr 10 2003

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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Greiner, E., Prisinzano, T., Johnson, E. M., Dersch, C. M., Marcus, J., Partilla, J. S., Rothman, R. B., Jacobson, A. E., & Rice, K. C. (2003). Structure-activity relationship studies of highly selective inhibitors of the dopamine transporter: N-benzylpiperidine analogues of 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl) piperazine. Journal of Medicinal Chemistry, 46(8), 1465-1469. https://doi.org/10.1021/jm020419v

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title = "Structure-activity relationship studies of highly selective inhibitors of the dopamine transporter: N-benzylpiperidine analogues of 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl) piperazine",

abstract = "A series of 4-[2-[bis(4-fluorophenyl)methoxy]ethyl-1-benzylpiperidines were examined for their ability to bind to the dopamine transporter (DAT), the serotonin transporter (SERT), and the norepinephrine transporter (NET). Binding results indicated that the presence of an electronwithdrawing group in the C4-position of the N-benzyl group is beneficial for binding to the DAT. Several analogues have been identified with high affinity for the DAT, up to 500-fold selectivity over the SERT and about 170-fold selectivity over the NET in binding and uptake inhibition assays.",

author = "Elisabeth Greiner and Thomas Prisinzano and Johnson, {Edward M.} and Dersch, {Christina M.} and Jamila Marcus and Partilla, {John S.} and Rothman, {Richard B.} and Jacobson, {Arthur E.} and Rice, {Kenner C.}",

year = "2003",

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day = "10",

doi = "10.1021/jm020419v",

language = "English",

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Greiner, E, Prisinzano, T, Johnson, EM, Dersch, CM, Marcus, J, Partilla, JS, Rothman, RB, Jacobson, AE & Rice, KC 2003, 'Structure-activity relationship studies of highly selective inhibitors of the dopamine transporter: N-benzylpiperidine analogues of 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl) piperazine', Journal of Medicinal Chemistry, vol. 46, no. 8, pp. 1465-1469. https://doi.org/10.1021/jm020419v

Structure-activity relationship studies of highly selective inhibitors of the dopamine transporter: N-benzylpiperidine analogues of 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl) piperazine. / Greiner, Elisabeth; Prisinzano, Thomas; Johnson, Edward M. et al.
In: Journal of Medicinal Chemistry, Vol. 46, No. 8, 10.04.2003, p. 1465-1469.

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

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AU - Greiner, Elisabeth

AU - Prisinzano, Thomas

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AU - Dersch, Christina M.

AU - Marcus, Jamila

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AU - Jacobson, Arthur E.

AU - Rice, Kenner C.

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Structure-activity relationship studies of highly selective inhibitors of the dopamine transporter: N-benzylpiperidine analogues of 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl) piperazine

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