Benzylideneoxymorphone: A new lead for development of bifunctional mu/delta opioid receptor ligands

• Published in: Bioorganic & medicinal chemistry letters Vol. 27; no. 3; pp. 666 - 669
• Main Authors: Healy, Jason R., Bezawada, Padmavani, Griggs, Nicholas W., Devereaux, Andrea L., Matsumoto, Rae R., Traynor, John R., Coop, Andrew, Cunningham, Christopher W.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.02.2017; Elsevier
• Subjects: Analgesic tolerance; Analgesics - chemical synthesis; Analgesics - chemistry; Analgesics - therapeutic use; Animals; Benzylidene Compounds - chemistry; Benzylideneoxymorphone; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Delta opioid receptor; Life Sciences & Biomedicine; Ligands; Mice; Mu opioid receptor; Oxymorphone; Oxymorphone - analogs & derivatives; Oxymorphone - chemical synthesis; Oxymorphone - chemistry; Oxymorphone - therapeutic use; Pain - drug therapy; Pharmacology & Pharmacy; Physical Sciences; Receptors, Opioid, delta - antagonists & inhibitors; Receptors, Opioid, delta - metabolism; Receptors, Opioid, mu - agonists; Receptors, Opioid, mu - metabolism; Science & Technology; Analgesic tolerance; Mu opioid receptor; Delta opioid receptor; Oxymorphone; Benzylideneoxymorphone; MORPHINE-TOLERANCE; MICE; MU AGONIST/DELTA ANTAGONIST; ANALGESICS; DEPENDENCE
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2016.11.057

[Display omitted] Opioid analgesic tolerance remains a considerable drawback to chronic pain management. The finding that concomitant administration of delta opioid receptor (DOR) antagonists attenuates the development of tolerance to mu opioid receptor (MOR) agonists has led to interest in producing bifunctional MOR agonist/DOR antagonist ligands. Herein, we present 7-benzylideneoxymorphone (6, UMB 246) displaying MOR partial agonist/DOR antagonist activity, representing a new lead for designing bifunctional MOR/DOR ligands.