Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1378947 | Bioorganic & Medicinal Chemistry Letters | 2005 | 6 Pages |
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.
Graphical abstractSynthetic strategies to improve the selectivity of the arylacetamide class of κ opioid agonists toward CYP2D6 is reported.Figure optionsDownload full-size imageDownload as PowerPoint slide
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
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,