Frankowski Kevin J, Ghosh Partha, Setola Vincent, Tran Thuy B, Roth Bryan L, Aubé Jeffrey
Department of Medicinal Chemistry, University of Kansas, 2121 Simons Drive, Lawrence, Kansas 66047.
ACS Med Chem Lett. 2010 Aug 12;1(5):189-193. doi: 10.1021/ml100040t.
Herein we report that N-alkyl-octahydroisoquinolin-1-one-8-carboxamides are a novel class of readily-synthesized, selective ϰ-opioid receptor (KOR) ligands. A striking feature of this class of compounds is the absence of any basic nitrogen atoms. Many of these compounds have demonstrated exclusive affinity for the KOR over not only the δ-opioid receptor (DOR) and the μ-opioid receptor (MOR), but 38 other GPCR targets as well. The general binding affinity of this class of compounds for the KOR combined with a streamlined route for analog synthesis provide strong motivation for pursuing this interesting new scaffold as a basis toward new probes targeting the KOR.
在此我们报告，N-烷基八氢异喹啉-1-酮-8-甲酰胺是一类新型的易于合成的选择性κ-阿片受体（KOR）配体。这类化合物的一个显著特征是不存在任何碱性氮原子。这些化合物中的许多不仅对KOR表现出比对δ-阿片受体（DOR）和μ-阿片受体（MOR）更高的亲和力，而且对其他38种G蛋白偶联受体（GPCR）靶点也具有专一性亲和力。这类化合物对KOR的一般结合亲和力，再加上类似物合成的简化路线，为探索这个有趣的新骨架作为开发靶向KOR的新探针的基础提供了强大动力。
