TY - JOUR
T1 - Extension of the Nenitzescu reaction to simple ketones provides an efficient route to 1′-alkyi-5′-hydroxynaltrindole analogues, potent and selective δ-opioid receptor antagonists
AU - Shefali,
AU - Srivastava, Sanjay K.
AU - Husbands, Stephen M.
AU - Lewis, John W.
PY - 2004/12/31
Y1 - 2004/12/31
N2 - The well-established Nenitzescu reaction of imines of β-dicarbonyl systems, as their enamine tautomers, with benzoquinone has been applied to a wide range of such imines to give 5-hydroxyindoles, some of which are of significant biological importance. This reaction has now been extended to the benzylimines of simple ketones, including those of the potent μ-opioid receptor antagonists naltrexone and naloxone. The products of the latter reactions, 1′-benzyl-5′-hydroxyindolomorphinans (7), are potent δ-opioid receptor (DOR) antagonists, confirming the enhancement of DOR antagonist potency and selectivity resulting from the introduction of the 1′-benzyl group.
AB - The well-established Nenitzescu reaction of imines of β-dicarbonyl systems, as their enamine tautomers, with benzoquinone has been applied to a wide range of such imines to give 5-hydroxyindoles, some of which are of significant biological importance. This reaction has now been extended to the benzylimines of simple ketones, including those of the potent μ-opioid receptor antagonists naltrexone and naloxone. The products of the latter reactions, 1′-benzyl-5′-hydroxyindolomorphinans (7), are potent δ-opioid receptor (DOR) antagonists, confirming the enhancement of DOR antagonist potency and selectivity resulting from the introduction of the 1′-benzyl group.
UR - http://www.scopus.com/inward/record.url?scp=12344299375&partnerID=8YFLogxK
U2 - 10.1021/jm040853s
DO - 10.1021/jm040853s
M3 - Article
AN - SCOPUS:12344299375
SN - 0022-2623
VL - 48
SP - 635
EP - 638
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 2
ER -