Arylacetamide κ opioid receptor agonists with reduced cytochrome P450 2D6 inhibitory activity

Bertrand Le Bourdonnec; Christopher W. Ajello; Pamela R. Seida; Roberta G. Susnow; Joel A. Cassel; Serge Belanger; Gabriel J. Stabley; Robert N. DeHaven; Diane L. DeHaven-Hudkins; Roland E. Dolle

doi:10.1016/j.bmcl.2005.03.020

Arylacetamide κ opioid receptor agonists with reduced cytochrome P450 2D6 inhibitory activity

Bertrand Le Bourdonnec
, Christopher W. Ajello
, Pamela R. Seida
, Roberta G. Susnow
, Joel A. Cassel
, Serge Belanger
, Gabriel J. Stabley
, Robert N. DeHaven
, Diane L. DeHaven-Hudkins
, Roland E. Dolle

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

18 Scopus citations

Abstract

Some κ opioid receptor agonists of the arylacetamide class, for example, ICI 199441 (1), were found to strongly inhibit the activity of cytochrome P450 2D6 (CYP2D6) (1: CYP2D6 IC₅₀ = 26 nM). Certain analogs bearing a substituted sulfonylamino group, for example, 13, were discovered to have significantly reduced CYP2D6 inhibitory activity (13: CYP2D6 IC₅₀ > 10 μM) while displaying high affinity toward the cloned human κ opioid receptor, good κ/δ and κ/μ selectivity, and potent in vitro and in vivo agonist activity.

Original language	English
Pages (from-to)	2647-2652
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	15
Issue number	10
DOIs	https://doi.org/10.1016/j.bmcl.2005.03.020
State	Published - May 16 2005

Keywords

CYP2D6
κ Opioid

Access to Document

10.1016/j.bmcl.2005.03.020

Cite this

Le Bourdonnec, B., Ajello, C. W., Seida, P. R., Susnow, R. G., Cassel, J. A., Belanger, S., Stabley, G. J., DeHaven, R. N., DeHaven-Hudkins, D. L., & Dolle, R. E. (2005). Arylacetamide κ opioid receptor agonists with reduced cytochrome P450 2D6 inhibitory activity. Bioorganic and Medicinal Chemistry Letters, 15(10), 2647-2652. https://doi.org/10.1016/j.bmcl.2005.03.020

@article{b757c0c6aced43669ecbbd8368bcb4cb,

title = "Arylacetamide κ opioid receptor agonists with reduced cytochrome P450 2D6 inhibitory activity",

abstract = "Some κ opioid receptor agonists of the arylacetamide class, for example, ICI 199441 (1), were found to strongly inhibit the activity of cytochrome P450 2D6 (CYP2D6) (1: CYP2D6 IC50 = 26 nM). Certain analogs bearing a substituted sulfonylamino group, for example, 13, were discovered to have significantly reduced CYP2D6 inhibitory activity (13: CYP2D6 IC50 > 10 μM) while displaying high affinity toward the cloned human κ opioid receptor, good κ/δ and κ/μ selectivity, and potent in vitro and in vivo agonist activity.",

keywords = "CYP2D6, κ Opioid",

author = "\{Le Bourdonnec\}, Bertrand and Ajello, \{Christopher W.\} and Seida, \{Pamela R.\} and Susnow, \{Roberta G.\} and Cassel, \{Joel A.\} and Serge Belanger and Stabley, \{Gabriel J.\} and DeHaven, \{Robert N.\} and DeHaven-Hudkins, \{Diane L.\} and Dolle, \{Roland E.\}",

year = "2005",

month = may,

day = "16",

doi = "10.1016/j.bmcl.2005.03.020",

language = "English",

volume = "15",

pages = "2647--2652",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

number = "10",

}

TY - JOUR

T1 - Arylacetamide κ opioid receptor agonists with reduced cytochrome P450 2D6 inhibitory activity

AU - Le Bourdonnec, Bertrand

AU - Ajello, Christopher W.

AU - Seida, Pamela R.

AU - Susnow, Roberta G.

AU - Cassel, Joel A.

AU - Belanger, Serge

AU - Stabley, Gabriel J.

AU - DeHaven, Robert N.

AU - DeHaven-Hudkins, Diane L.

AU - Dolle, Roland E.

PY - 2005/5/16

Y1 - 2005/5/16

N2 - Some κ opioid receptor agonists of the arylacetamide class, for example, ICI 199441 (1), were found to strongly inhibit the activity of cytochrome P450 2D6 (CYP2D6) (1: CYP2D6 IC50 = 26 nM). Certain analogs bearing a substituted sulfonylamino group, for example, 13, were discovered to have significantly reduced CYP2D6 inhibitory activity (13: CYP2D6 IC50 > 10 μM) while displaying high affinity toward the cloned human κ opioid receptor, good κ/δ and κ/μ selectivity, and potent in vitro and in vivo agonist activity.

AB - Some κ opioid receptor agonists of the arylacetamide class, for example, ICI 199441 (1), were found to strongly inhibit the activity of cytochrome P450 2D6 (CYP2D6) (1: CYP2D6 IC50 = 26 nM). Certain analogs bearing a substituted sulfonylamino group, for example, 13, were discovered to have significantly reduced CYP2D6 inhibitory activity (13: CYP2D6 IC50 > 10 μM) while displaying high affinity toward the cloned human κ opioid receptor, good κ/δ and κ/μ selectivity, and potent in vitro and in vivo agonist activity.

KW - CYP2D6

KW - κ Opioid

UR - https://www.scopus.com/pages/publications/20944445103

U2 - 10.1016/j.bmcl.2005.03.020

DO - 10.1016/j.bmcl.2005.03.020

M3 - Article

C2 - 15863335

AN - SCOPUS:20944445103

SN - 0960-894X

VL - 15

SP - 2647

EP - 2652

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 10

ER -

Arylacetamide κ opioid receptor agonists with reduced cytochrome P450 2D6 inhibitory activity

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this