Synthesis and biological activity of 8β-substituted hydrocodone indole and hydromorphone indole derivatives

Han Yu; Thomas Prisinzano; Christina M. Dersch; Jamila Marcus; Richard B. Rothman; Arthur E. Jacobson; Kenner C. Rice

doi:10.1016/S0960-894X(01)00689-8

Synthesis and biological activity of 8β-substituted hydrocodone indole and hydromorphone indole derivatives

Han Yu, Thomas Prisinzano, Christina M. Dersch, Jamila Marcus, Richard B. Rothman, Arthur E. Jacobson, Kenner C. Rice

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

26 Scopus citations

Abstract

The 8β-unsubstituted and substituted analogues of hydrocodone indole and hydromorphone indole were synthesized and their binding affinities to opioid receptors were determined. Introduction of an 8β-methyl group into the indolomorphinan nucleus increased affinity at all opioid receptors. 6,7-Dehydro-4,5α-epoxy-8β-methyl-6,7,2′,3′- indolomorphinan (9) was found to be a δ antagonist with subnanomolar affinity (0.7 nM) for the δ-opioid receptor, and to have good δ-selectivity (μ/δ=322).

Original language	English
Pages (from-to)	165-168
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	12
Issue number	2
DOIs	https://doi.org/10.1016/S0960-894X(01)00689-8
State	Published - Jan 21 2002

Bibliographical note

Funding Information:
The authors would like to thank Noel Whittaker of the Laboratory of Bioorganic Chemistry, NIDDK for mass spectral data. Partial support of this work is by the National Institute on Drug Abuse.

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/S0960-894X(01)00689-8

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title = "Synthesis and biological activity of 8β-substituted hydrocodone indole and hydromorphone indole derivatives",

abstract = "The 8β-unsubstituted and substituted analogues of hydrocodone indole and hydromorphone indole were synthesized and their binding affinities to opioid receptors were determined. Introduction of an 8β-methyl group into the indolomorphinan nucleus increased affinity at all opioid receptors. 6,7-Dehydro-4,5α-epoxy-8β-methyl-6,7,2′,3′- indolomorphinan (9) was found to be a δ antagonist with subnanomolar affinity (0.7 nM) for the δ-opioid receptor, and to have good δ-selectivity (μ/δ=322).",

author = "Han Yu and Thomas Prisinzano and Dersch, {Christina M.} and Jamila Marcus and Rothman, {Richard B.} and Jacobson, {Arthur E.} and Rice, {Kenner C.}",

note = "Funding Information: The authors would like to thank Noel Whittaker of the Laboratory of Bioorganic Chemistry, NIDDK for mass spectral data. Partial support of this work is by the National Institute on Drug Abuse.",

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AU - Yu, Han

AU - Prisinzano, Thomas

AU - Dersch, Christina M.

AU - Marcus, Jamila

AU - Rothman, Richard B.

AU - Jacobson, Arthur E.

AU - Rice, Kenner C.

N1 - Funding Information: The authors would like to thank Noel Whittaker of the Laboratory of Bioorganic Chemistry, NIDDK for mass spectral data. Partial support of this work is by the National Institute on Drug Abuse.

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Y1 - 2002/1/21

N2 - The 8β-unsubstituted and substituted analogues of hydrocodone indole and hydromorphone indole were synthesized and their binding affinities to opioid receptors were determined. Introduction of an 8β-methyl group into the indolomorphinan nucleus increased affinity at all opioid receptors. 6,7-Dehydro-4,5α-epoxy-8β-methyl-6,7,2′,3′- indolomorphinan (9) was found to be a δ antagonist with subnanomolar affinity (0.7 nM) for the δ-opioid receptor, and to have good δ-selectivity (μ/δ=322).

AB - The 8β-unsubstituted and substituted analogues of hydrocodone indole and hydromorphone indole were synthesized and their binding affinities to opioid receptors were determined. Introduction of an 8β-methyl group into the indolomorphinan nucleus increased affinity at all opioid receptors. 6,7-Dehydro-4,5α-epoxy-8β-methyl-6,7,2′,3′- indolomorphinan (9) was found to be a δ antagonist with subnanomolar affinity (0.7 nM) for the δ-opioid receptor, and to have good δ-selectivity (μ/δ=322).

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Synthesis and biological activity of 8β-substituted hydrocodone indole and hydromorphone indole derivatives

Abstract

Bibliographical note

ASJC Scopus subject areas

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