Arylacetamide κ opioid receptor agonists with reduced cytochrome P450 2D6 inhibitory activity
| Autor: | Serge Belanger, Roland E. Dolle, Christopher W. Ajello, Bertrand Le Bourdonnec, Roberta G. Susnow, Pamela R. Seida, Robert N. DeHaven, Diane L. DeHaven-Hudkins, Gabriel J. Stabley, Joel A. Cassel |
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| Rok vydání: | 2005 |
| Předmět: |
Agonist
medicine.drug_class Stereochemistry Clinical Biochemistry Pharmaceutical Science Pharmacology digestive system Biochemistry Substrate Specificity In vivo Opioid receptor Cytochrome P-450 CYP2D6 Inhibitors Acetamides Drug Discovery medicine Enzyme Inhibitors skin and connective tissue diseases Molecular Biology chemistry.chemical_classification Unspecific monooxygenase biology Receptors Opioid kappa Organic Chemistry Cytochrome P450 Biological activity In vitro Enzyme chemistry biology.protein Molecular Medicine |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 15:2647-2652 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2005.03.020 |
| Popis: | Some kappa 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 IC5010 microM) while displaying high affinity toward the cloned human kappa opioid receptor, good kappa/delta and kappa/mu selectivity, and potent in vitro and in vivo agonist activity. |
| Databáze: | OpenAIRE |
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