TY - JOUR
T1 - Enantiomeric (-)-(1R,5R,9R) and (+)-(1S,5S,9S) heterocyclic N-substituted-normetazocines
T2 - Synthesis of potent and selective antinociceptives and opioid antagonists through N-substituent modification
AU - May, E. L.
AU - Aceto, M. D.
AU - Bowman, E. R.
AU - Traynor, J. R.
AU - Woods, J. H.
AU - Jacobson, A. E.
AU - Harris, L. S.
PY - 2000
Y1 - 2000
N2 - A number of diverse N-substituted-N-normetazocine heterocycles ((-)-1R,5R,9R)- and (+)-(1S,5S,9S)-5,9-dimethyl-2′-hydroxy-2-substituted-6,7-benzomorphans) were synthesized and evaluated. Conversion of an antinociceptively inactive alcohol to an ether (-)-1R,5R,9R)-5,9-dimethyl-2′-hydroxy-2-(2-methoxyethyl)-6,7-benzomorph an ((-)-N-methoxyethylnormetazocine, 4), gave a compound that was 10 to 40 times more potent than morphine as an antinociceptive agent, but did not attenuate morphine withdrawal in monkeys. Other (-)-enantiomers also had potent antinociceptive activity and one, (-)-N-fluoropropylnormetazocine (9), was a potent opioid antagonist.
AB - A number of diverse N-substituted-N-normetazocine heterocycles ((-)-1R,5R,9R)- and (+)-(1S,5S,9S)-5,9-dimethyl-2′-hydroxy-2-substituted-6,7-benzomorphans) were synthesized and evaluated. Conversion of an antinociceptively inactive alcohol to an ether (-)-1R,5R,9R)-5,9-dimethyl-2′-hydroxy-2-(2-methoxyethyl)-6,7-benzomorph an ((-)-N-methoxyethylnormetazocine, 4), gave a compound that was 10 to 40 times more potent than morphine as an antinociceptive agent, but did not attenuate morphine withdrawal in monkeys. Other (-)-enantiomers also had potent antinociceptive activity and one, (-)-N-fluoropropylnormetazocine (9), was a potent opioid antagonist.
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M3 - Article
AN - SCOPUS:0034545151
VL - 10
SP - 178
EP - 185
JO - Medicinal Chemistry Research
JF - Medicinal Chemistry Research
SN - 1054-2523
IS - 3
ER -