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

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Organic Chemistry

Background:

• The benzomorphan skeleton is primarily recognized for its application in developing opioid analgesics.
• However, its structural versatility suggests potential beyond this traditional role.

Purpose of the Study:

• To review the structure-activity relationships (SARs) of benzomorphan derivatives targeting various receptors and channels.
• To highlight the benzomorphan nucleus as a valuable scaffold for novel drug discovery.

Main Methods:

• Literature review of SAR studies on benzomorphan-based compounds.
• Analysis of modifications at the phenolic hydroxyl group and basic nitrogen.
• Examination of compound interactions with sigma 1 receptor (σ1R), sigma 2 receptor (σ2R), voltage-dependent sodium channels, and N-Methyl-d-Aspartate (NMDA) receptor-channel complex.

Main Results:

• Stereochemistry and specific modifications are crucial for directing benzomorphan compounds to particular biological targets.
• SAR data reveal interactions with σ1R, σ2R, sodium channels, and NMDA receptor-channel complex.
• The benzomorphan scaffold demonstrates broad applicability in medicinal chemistry.

Conclusions:

• The benzomorphan nucleus is a highly adaptable template for synthesizing drug candidates.
• Its potential extends to various therapeutic areas beyond opioid analgesia.
• Further exploration of benzomorphan derivatives is warranted for diverse pharmacological targets.