Department of Chemistry "G. Ciamician" , University of Bologna , Via Selmi 2 , 40126 Bologna , Italy.
Department of Pharmacy and Biotechnology , University of Bologna , Via Irnerio 48 , 40126 Bologna , Italy.
J Med Chem. 2018 Jul 12;61(13):5751-5757. doi: 10.1021/acs.jmedchem.8b00296. Epub 2018 Jul 2.
Herein we present the expedient synthesis of endomorphin-1 analogues containing stereoisomeric β-homo-Freidinger lactam-like scaffolds ([Amo]EM), and we discuss opioid receptor (OR) affinity, enzymatic stability, functional activity, in vivo antinociceptive effects, and conformational and molecular docking analysis. Hence, H-Tyr-Amo-Trp-PheNH resulted to be a new chemotype of highly stable, selective, partial KOR agonist inducing analgesia, therefore displaying great potential interest as a painkiller possibly with reduced harmful side effects.
在此，我们提出了包含立体异构β-同型-Freidinger 内酰胺样支架的内吗啡肽-1 类似物（[Amo]EM）的便捷合成方法，并讨论了阿片受体（OR）亲和力、酶稳定性、功能活性、体内镇痛作用以及构象和分子对接分析。因此，H-Tyr-Amo-Trp-PheNH 是一种新型的高度稳定、选择性、部分 KOR 激动剂，具有诱导镇痛作用，因此显示出作为一种潜在的止痛药的巨大兴趣，可能具有减少有害副作用。
