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

…, RN DeHaven, DL DeHaven-Hudkins, RE Dolle

Index: Le Bourdonnec, Bertrand; Ajello, Christopher W.; Seida, Pamela R.; Susnow, Roberta G.; Cassel, Joel A.; Belanger, Serge; Stabley, Gabriel J.; DeHaven, Robert N.; DeHaven-Hudkins, Diane L.; Dolle, Roland E. Bioorganic and Medicinal Chemistry Letters, 2005 , vol. 15, # 10 p. 2647 - 2652

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Citation Number: 14

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= 26nM). Certain analogs bearing a substituted sulfonylamino group, for example, 13, were discovered to have significantly reduced CYP2D6 inhibitory activity (13: CYP2D6 IC50> 10μM) while displaying high affinity toward the cloned human κ opioid receptor, ...