Enantiomeric (-)-(1R,5R,9R) and (+)-(1S,5S,9S) heterocyclic N-substituted-normetazocines: Synthesis of potent and selective antinociceptives and opioid antagonists through N-substituent modification

E. L. May; M. D. Aceto; E. R. Bowman; J. R. Traynor; J. H. Woods; A. E. Jacobson; L. S. Harris

Enantiomeric (-)-(1R,5R,9R) and (+)-(1S,5S,9S) heterocyclic N-substituted-normetazocines: Synthesis of potent and selective antinociceptives and opioid antagonists through N-substituent modification

E. L. May, M. D. Aceto, E. R. Bowman, J. R. Traynor, J. H. Woods, A. E. Jacobson, L. S. Harris

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Pages (from-to)	178-185
Number of pages	8
Journal	Medicinal Chemistry Research
Volume	10
Issue number	3
State	Published - 2000
Externally published	Yes

ASJC Scopus subject areas

Pharmacology, Toxicology and Pharmaceutics(all)
Organic Chemistry

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Enantiomeric (-)-(1R,5R,9R) and (+)-(1S,5S,9S) heterocyclic N-substituted-normetazocines : Synthesis of potent and selective antinociceptives and opioid antagonists through N-substituent modification. / May, E. L.; Aceto, M. D.; Bowman, E. R.; Traynor, J. R.; Woods, J. H.; Jacobson, A. E.; Harris, L. S.

In: Medicinal Chemistry Research, Vol. 10, No. 3, 2000, p. 178-185.

Research output: Contribution to journal › Article › peer-review

May, E. L. ; Aceto, M. D. ; Bowman, E. R. ; Traynor, J. R. ; Woods, J. H. ; Jacobson, A. E. ; Harris, L. S. / Enantiomeric (-)-(1R,5R,9R) and (+)-(1S,5S,9S) heterocyclic N-substituted-normetazocines : Synthesis of potent and selective antinociceptives and opioid antagonists through N-substituent modification. In: Medicinal Chemistry Research. 2000 ; Vol. 10, No. 3. pp. 178-185.

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abstract = "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.",

author = "May, {E. L.} and Aceto, {M. D.} and Bowman, {E. R.} and Traynor, {J. R.} and Woods, {J. H.} and Jacobson, {A. E.} and Harris, {L. S.}",

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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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Enantiomeric (-)-(1R,5R,9R) and (+)-(1S,5S,9S) heterocyclic N-substituted-normetazocines: Synthesis of potent and selective antinociceptives and opioid antagonists through N-substituent modification

Abstract

ASJC Scopus subject areas

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