Cheminformatic Analysis of Core-Atom Transformations in Pharmaceutically Relevant Heteroaromatics

Area of Science:

• Medicinal Chemistry
• Computational Chemistry
• Drug Discovery

Background:

• Heteroaromatics are fundamental scaffolds in pharmaceutical development.
• Modifying these core structures, known as skeletal edits, can significantly broaden accessible chemical diversity.
• The quantitative impact of skeletal edits on chemical space remains largely unexplored.

Purpose of the Study:

• To develop a cheminformatic platform for analyzing skeletal edits in heteroaromatics.
• To quantitatively assess which core-atom transformations maximize access to novel chemical space.
• To provide a framework for prioritizing skeletal modifications in drug discovery.

Main Methods:

• Development of a cheminformatic platform.
• Analysis of single and multiple core-atom transformations.
• Quantitative assessment of impact on chemical space.

Main Results:

• Identification of skeletal edits that most effectively expand novel chemical space.
• Demonstration of the significance of heteroaromatic core-atom transformations for chemical diversity.
• Establishment of a quantitative framework for prioritizing these modifications.

Conclusions:

• Emerging single and multiple core-atom transformations are crucial for enhancing heteroaromatic chemical diversity.
• The developed platform provides a quantitative basis for selecting impactful skeletal edits.
• Further development of methods for these transformations is warranted to accelerate drug discovery.