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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:27

Article

Healy, Jason R.^1,2  Bezawada, Padmavani³  Griggs, Nicholas W.⁴  Devereaux, Andrea L.⁵  Matsumoto, Rae R.^1,6  Traynor, John R.⁴  Coop, Andrew³  Cunningham, Christopher W.⁵ 

[1] West Virginia Univ, Sch Pharm, Dept Basic Pharmaceut Sci, Hlth Sci North 2036, Morgantown, WV 26506 USA

[2] Thomas Jefferson Univ, Dept Pharmacol & Expt Therapeut, 1170 Main Bldg,132 S 10th St, Philadelphia, PA 19107 USA

[3] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, 20 Penn St, Baltimore, MD 21201 USA

[4] Univ Michigan, Sch Med, Dept Pharmacol, 1220A MSRB, Ann Arbor, MI 48109 USA

[5] Concordia Univ Wisconsin, Sch Pharm, Dept Pharmaceut Sci, 12800 N Lake Shore Dr, Mequon, WI 53097 USA

[6] Touro Univ Calif, Coll Pharm, Dept Biol & Pharmaceut Sci, 1310 Club Dr, Vallejo, CA 94592 USA

关键词: Mu opioid receptor;    Delta opioid receptor;    Analgesic tolerance;    Oxymorphone;    Benzylideneoxymorphone;   

DOI  :  10.1016/j.bmcl.2016.11.057

来源: Elsevier

【 摘 要 】

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. (C) 2016 Elsevier Ltd. All rights reserved.

【 授权许可】

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