Rings in Clinical Trials and Drugs: Present and Future.

Area of Science:

• Medicinal Chemistry
• Drug Discovery
• Computational Chemistry

Background:

• Ring systems are fundamental scaffolds in medicinal chemistry and drug discovery.
• Understanding the diversity and utilization of ring systems is crucial for identifying novel therapeutic agents.
• Existing research indicates a reliance on known scaffolds in drug development.

Purpose of the Study:

• To comprehensively analyze ring systems in clinical trial compounds and FDA-approved drugs.
• To assess the novelty and diversity of ring systems utilized in drug discovery.
• To predict future trends in ring system utilization for novel drug development.

Main Methods:

• Analysis of ring systems in a large dataset of clinical trial compounds and FDA-approved drugs.
• Comparison of utilized ring systems against the broader synthesized chemical space.
• Systematic modification of existing ring systems to predict future candidates.

Main Results:

• 67% of small molecules in clinical trials utilize ring systems already present in marketed drugs.
• Clinical trial molecules represent only 0.1% of the vast available synthesized chemical space (approx. 450,000 unique ring systems).
• Drug development shows fewer unique ring systems than clinical trials, but higher reuse rates; systematic modifications predict 3902 future ring systems.

Conclusions:

• Drug discovery heavily relies on established ring systems, with limited exploration of novel chemical space.
• The reuse of known ring systems in approved drugs suggests an optimization strategy.
• Predictive modeling of modified ring systems offers a pathway to explore novel scaffolds for future clinical trials.