亚苄基羟吗啡酮：一种开发双功能μ/δ阿片受体配体的新先导化合物。
Benzylideneoxymorphone: A new lead for development of bifunctional mu/delta opioid receptor ligands.
作者信息
Healy Jason R, Bezawada Padmavani, Griggs Nicholas W, Devereaux Andrea L, Matsumoto Rae R, Traynor John R, Coop Andrew, Cunningham Christopher W
机构信息
Department of Basic Pharmaceutical Sciences, West Virginia University School of Pharmacy, 2036 Health Sciences North, Morgantown, WV 26506, USA; Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, 1170 Main Bldg., 132 S. 10th St., Philadelphia, PA 19107, USA.
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 Penn Street, Baltimore, MD 21201, USA.
出版信息
Bioorg Med Chem Lett. 2017 Feb 1;27(3):666-669. doi: 10.1016/j.bmcl.2016.11.057. Epub 2016 Nov 22.
Abstract
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.
摘要
阿片类镇痛药耐受性仍然是慢性疼痛管理中的一个重大缺陷。发现同时给予δ阿片受体（DOR）拮抗剂可减弱对μ阿片受体（MOR）激动剂耐受性的发展，这引发了人们对生产双功能MOR激动剂/DOR拮抗剂配体的兴趣。在此，我们展示了7-亚苄基氧吗啡酮（6，UMB 246）具有MOR部分激动剂/DOR拮抗剂活性，它代表了设计双功能MOR/DOR配体的一个新先导化合物。
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