Department of Drug Sciences, Medicinal Chemistry Section, University of Catania, Viale A. Doria, 6, 95100, Catania, Italy.
Department of Drug Sciences, Pharmaceutical Technology Section, University of Catania, Viale A. Doria 6, 95125, Catania, Italy.
Eur J Med Chem. 2018 Jul 15;155:492-502. doi: 10.1016/j.ejmech.2018.06.017. Epub 2018 Jun 7.
Despite the fact that the benzomorphan skeleton has mainly been employed in medicinal chemistry for the development of opioid analgesics, it is a versatile structure. Its stereochemistry, as well as opportune modifications at the phenolic hydroxyl group and at the basic nitrogen, play a pivotal role addressing the benzomorphan-based compounds to a specific target. In this review, we describe the structure activity-relationships (SARs) of benzomorphan-based compounds acting at sigma 1 receptor (σ1R), sigma 2 receptor (σ2R), voltage-dependent sodium channel, N-Methyl-d-Aspartate (NMDA) receptor-channel complex and other targets. Collectively, the SARs data have highlighted that the benzomorphan nucleus could be regarded as a useful template for the synthesis of drug candidates for different targets.
尽管苯并吗啡烷骨架主要用于开发阿片类镇痛药的药物化学，但它是一种多功能结构。其立体化学以及酚羟基和碱性氮的适时修饰，对于将苯并吗啡烷类化合物靶向特定靶标起着至关重要的作用。在这篇综述中，我们描述了苯并吗啡烷类化合物在 sigma 1 受体（σ1R）、sigma 2 受体（σ2R）、电压门控钠离子通道、N-甲基-D-天冬氨酸（NMDA）受体-通道复合物和其他靶点上的构效关系（SAR）。总的来说，SAR 数据表明，苯并吗啡烷核可以被视为合成针对不同靶点的候选药物的有用模板。
