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 -