Selective opioid growth factor receptor antagonists based on a stilbene isostere

David P Stockdale; Michelle B Titunick; Jessica M Biegler; Jessie L Reed; Alyssa M Hartung; David F Wiemer; Patricia J McLaughlin; Jeffrey D Neighbors

doi:10.1016/j.bmc.2017.06.035

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Selective opioid growth factor receptor antagonists based on a stilbene isostere

Journal article

Peer reviewed

Selective opioid growth factor receptor antagonists based on a stilbene isostere

David P Stockdale, Michelle B Titunick, Jessica M Biegler, Jessie L Reed, Alyssa M Hartung, David F Wiemer, Patricia J McLaughlin and Jeffrey D Neighbors

Bioorganic & medicinal chemistry, Vol.25(16), pp.4464-4474

08/15/2017

DOI: 10.1016/j.bmc.2017.06.035

PMCID: PMC5567982

PMID: 28693915

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https://www.ncbi.nlm.nih.gov/pmc/articles/5567982View

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Abstract

[Display omitted] As part of an ongoing drug development effort aimed at selective opioid receptor ligands based on the pawhuskin natural products we have synthesized a small set of amide isosteres. These amides were centered on lead compounds which are selective antagonists for the delta and kappa opioid receptors. The amide isomers revealed here show dramatically different activity from the parent stilbene compounds. Three of the isomers synthesized showed antagonist activity for the opioid growth factor (OGF)/opioid growth factor receptor (OGFR) axis which is involved in cellular and organ growth control. This cellular signaling mechanism is targeted by “low-dose” naltrexone therapy which is being tested clinically for multiple sclerosis, Crohn’s disease, cancer, and wound healing disorders. The compounds described here are the first selective small molecule ligands for the OGF/OGFR system and will serve as important leads and probes for further study.

Pawhuskin

Low-dose naltrexone

Opioid growth factor

Opioid receptor

Stilbene isostere

Details

Title: Subtitle: Selective opioid growth factor receptor antagonists based on a stilbene isostere
Creators: David P Stockdale - Department of Chemistry, The University of Iowa, Iowa City, IA 52242-1294, United States
Michelle B Titunick - Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, Hershey, PA 17033, United States
Jessica M Biegler - Department of Pharmacology and Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, United States
Jessie L Reed - Department of Pharmacology and Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, United States
Alyssa M Hartung - Department of Chemistry, The University of Iowa, Iowa City, IA 52242-1294, United States
David F Wiemer - Department of Chemistry, The University of Iowa, Iowa City, IA 52242-1294, United States
Patricia J McLaughlin - Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, Hershey, PA 17033, United States
Jeffrey D Neighbors - Department of Pharmacology and Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, United States
Resource Type: Journal article
Publication Details: Bioorganic & medicinal chemistry, Vol.25(16), pp.4464-4474
DOI: 10.1016/j.bmc.2017.06.035
PMID: 28693915
PMCID: PMC5567982
NLM abbreviation: Bioorg Med Chem
ISSN: 0968-0896
eISSN: 1464-3391
Publisher: Elsevier Ltd
Grant note: DOI: 10.13039/100001024, name: Roy J. Carver Charitable Trust
Language: English
Date published: 08/15/2017
Academic Unit: Neuroscience and Pharmacology; Chemistry
Record Identifier: 9983985844802771

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