Fsp³: A new parameter for drug-likeness

Area of Science:

• Medicinal Chemistry
• Drug Discovery
• Organic Synthesis

Background:

• Drug-likeness is crucial in early drug discovery, defined by compound similarity to existing drugs.
• The fraction of sp3 carbon atoms (Fsp3) is a key metric influencing drug-likeness.
• Improving Fsp3 content is a strategic goal in medicinal chemistry.

Purpose of the Study:

• To collate and review research on the fraction of sp3 carbon atoms (Fsp3) in drug discovery.
• To explore high-throughput screening (HTS) applications related to Fsp3.
• To present novel synthetic strategies for spirocyclic scaffolds to enhance Fsp3.

Main Methods:

• Literature review of Fsp3 in drug discovery and medicinal chemistry.
• Analysis of structural modifications and strategies to improve Fsp3.
• Introduction of new synthetic methodologies for spirocyclic compounds.

Main Results:

• Fsp3 content is a significant determinant of compound drug-likeness.
• High-throughput screening (HTS) provides valuable data for Fsp3 optimization.
• New synthetic routes enable access to spirocyclic scaffolds with tunable Fsp3.

Conclusions:

• Spirocyclic scaffolds possess inherent rigidity beneficial for drug design.
• Optimizing Fsp3 through structural modification and synthesis is vital for drug discovery.
• Spirocyclic scaffolds represent a promising avenue for developing a new generation of drug candidates.