Verifying the role of 3-hydroxy of 17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[(4'-pyridyl) carboxamido]morphinan derivatives via their binding affinity and selectivity profiles on opioid receptors.


Journal

Bioorganic chemistry
ISSN: 1090-2120
Titre abrégé: Bioorg Chem
Pays: United States
ID NLM: 1303703

Informations de publication

Date de publication:
04 2021
Historique:
received: 16 07 2020
revised: 10 09 2020
accepted: 28 01 2021
pubmed: 26 2 2021
medline: 1 10 2021
entrez: 25 2 2021
Statut: ppublish

Résumé

In the present study, the role of 3-hydroxy group of a series of epoxymorphinan derivatives in their binding affinity and selectivity profiles toward the opioid receptors (ORs) has been investigated. It was found that the 3-hydroxy group was crucial for the binding affinity of these derivatives for all three ORs due to the fact that all the analogues 1a-e exhibited significantly higher binding affinities compared to their counterpart 3-dehydroxy ones 6a-e. Meanwhile most compounds carrying the 3-hydroxy group possessed similar selectivity profiles for the kappa opioid receptor over the mu opioid receptor as their corresponding 3-dehydroxy derivatives. [

Identifiants

pubmed: 33631465
pii: S0045-2068(21)00078-X
doi: 10.1016/j.bioorg.2021.104702
pmc: PMC8009840
mid: NIHMS1676179
pii:
doi:

Substances chimiques

Morphinans 0
Receptors, Opioid 0

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

104702

Subventions

Organisme : NIDA NIH HHS
ID : P30 DA013429
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA024022
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA041359
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA044855
Pays : United States
Organisme : NIDA NIH HHS
ID : R21 DA045274
Pays : United States
Organisme : NIDA NIH HHS
ID : UG3 DA050311
Pays : United States

Informations de copyright

Copyright © 2021 Elsevier Inc. All rights reserved.

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Auteurs

Boshi Huang (B)

Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 800 E Leigh Street, Richmond, VA 23298, United States.

Rama Gunta (R)

Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 800 E Leigh Street, Richmond, VA 23298, United States.

Huiqun Wang (H)

Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 800 E Leigh Street, Richmond, VA 23298, United States.

Mengchu Li (M)

Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 800 E Leigh Street, Richmond, VA 23298, United States.

Danni Cao (D)

Center for Substance Abuse Research and Department of Pharmacology, Lewis Katz School of Medicine, Temple University, 3500 North Broad Street, MERB 851, Philadelphia, PA 19140, United States; Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.

Rolando E Mendez (RE)

Department of Pharmacology and Toxicology, Virginia Commonwealth University, 410 North 12th Street, Richmond, VA 23298, United States.

James C Gillespie (JC)

Department of Pharmacology and Toxicology, Virginia Commonwealth University, 410 North 12th Street, Richmond, VA 23298, United States.

Chongguang Chen (C)

Center for Substance Abuse Research and Department of Pharmacology, Lewis Katz School of Medicine, Temple University, 3500 North Broad Street, MERB 851, Philadelphia, PA 19140, United States.

Lan-Hsuan M Huang (LM)

Center for Substance Abuse Research and Department of Pharmacology, Lewis Katz School of Medicine, Temple University, 3500 North Broad Street, MERB 851, Philadelphia, PA 19140, United States.

Lee-Yuan Liu-Chen (LY)

Center for Substance Abuse Research and Department of Pharmacology, Lewis Katz School of Medicine, Temple University, 3500 North Broad Street, MERB 851, Philadelphia, PA 19140, United States.

Dana E Selley (DE)

Department of Pharmacology and Toxicology, Virginia Commonwealth University, 410 North 12th Street, Richmond, VA 23298, United States.

Yan Zhang (Y)

Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 800 E Leigh Street, Richmond, VA 23298, United States. Electronic address: yzhang2@vcu.edu.

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Classifications MeSH