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

Research output: Contribution to journalArticle

Abstract

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.

LanguageEnglish (US)
Pages4464-4474
Number of pages11
JournalBioorganic and Medicinal Chemistry
Volume25
Issue number16
DOIs
StatePublished - Jan 1 2017

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Stilbenes
Amides
Isomers
Opioid Analgesics
Intercellular Signaling Peptides and Proteins
Cell signaling
Ligands
Lead compounds
kappa Opioid Receptor
Naltrexone
delta Opioid Receptor
Narcotic Antagonists
Opioid Receptors
Biological Products
Crohn Disease
Wound Healing
Multiple Sclerosis
Molecules
Growth
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

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

Cite this

Stockdale, D. P., Titunick, M. B., Biegler, J. M., Reed, J. L., Hartung, A. M., Wiemer, D. F., ... Neighbors, J. D. (2017). Selective opioid growth factor receptor antagonists based on a stilbene isostere. Bioorganic and Medicinal Chemistry, 25(16), 4464-4474. DOI: 10.1016/j.bmc.2017.06.035
Stockdale, David P. ; Titunick, Michelle B. ; Biegler, Jessica M. ; Reed, Jessie L. ; Hartung, Alyssa M. ; Wiemer, David F. ; McLaughlin, Patricia J. ; Neighbors, Jeffrey D./ Selective opioid growth factor receptor antagonists based on a stilbene isostere. In: Bioorganic and Medicinal Chemistry. 2017 ; Vol. 25, No. 16. pp. 4464-4474
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Stockdale, DP, Titunick, MB, Biegler, JM, Reed, JL, Hartung, AM, Wiemer, DF, McLaughlin, PJ & Neighbors, JD 2017, 'Selective opioid growth factor receptor antagonists based on a stilbene isostere' Bioorganic and Medicinal Chemistry, vol. 25, no. 16, pp. 4464-4474. DOI: 10.1016/j.bmc.2017.06.035

Selective opioid growth factor receptor antagonists based on a stilbene isostere. / Stockdale, David P.; Titunick, Michelle B.; Biegler, Jessica M.; Reed, Jessie L.; Hartung, Alyssa M.; Wiemer, David F.; McLaughlin, Patricia J.; Neighbors, Jeffrey D.

In: Bioorganic and Medicinal Chemistry, Vol. 25, No. 16, 01.01.2017, p. 4464-4474.

Research output: Contribution to journalArticle

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Stockdale DP, Titunick MB, Biegler JM, Reed JL, Hartung AM, Wiemer DF et al. Selective opioid growth factor receptor antagonists based on a stilbene isostere. Bioorganic and Medicinal Chemistry. 2017 Jan 1;25(16):4464-4474. Available from, DOI: 10.1016/j.bmc.2017.06.035