Pharmaceuticals that contain polycyclic hydrocarbon scaffolds

Area of Science:

• Medicinal Chemistry
• Organic Chemistry
• Pharmacology

Background:

• Pharmaceutical compounds exhibit diverse structural motifs developed over decades.
• Caged (bridged) bicyclic structures offer unique 3D shapes and pharmacokinetic properties.
• These motifs are prevalent in numerous drugs, including top-selling pharmaceuticals.

Purpose of the Study:

• To review approximately 20 all-carbon cage pharmaceuticals.
• To explore the history, biology, and synthetic methods of these compounds.
• To analyze the role of natural products versus synthetic systems in drug discovery.

Main Methods:

• Literature review of existing pharmaceuticals containing all-carbon cage structures.
• Survey of synthetic methodologies for constructing bicyclic motifs.
• Comparative analysis of natural product and de novo synthetic approaches.

Main Results:

• Identified around 20 all-carbon cage pharmaceuticals, from bicyclo[2.2.1] to adamantane.
• Many of these lipophilic compounds exhibit central nervous system (CNS) and/or neurological activity.
• Discussed synthetic routes and provided historical and biological context for each drug.

Conclusions:

• All-carbon cage structures are valuable scaffolds in drug development, particularly for CNS-related conditions.
• Synthetic strategies for these rigid systems are crucial for pharmaceutical innovation.
• Further exploration of caged hydrocarbons may yield novel therapeutic agents, moving beyond simpler molecular designs.