Benzomorphan skeleton, a versatile scaffold for different targets: A comprehensive review

Eur J Med Chem. 2018 Jul 15:155:492-502. doi: 10.1016/j.ejmech.2018.06.017. Epub 2018 Jun 7.

Abstract

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.

Keywords: Antiviral; NMDA; Neuroprotection; Opioid; Sigma receptor; Sodium channel.

Publication types

  • Review

MeSH terms

  • Analgesics, Opioid / chemical synthesis
  • Analgesics, Opioid / chemistry
  • Analgesics, Opioid / pharmacology*
  • Animals
  • Benzomorphans / chemical synthesis
  • Benzomorphans / chemistry
  • Benzomorphans / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • NAV1.2 Voltage-Gated Sodium Channel / metabolism*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Receptors, sigma / antagonists & inhibitors*
  • Sigma-1 Receptor
  • Structure-Activity Relationship

Substances

  • Analgesics, Opioid
  • Benzomorphans
  • NAV1.2 Voltage-Gated Sodium Channel
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, sigma
  • sigma-2 receptor