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Exploring aromatic chemical space with NEAT: novel and electronically equivalent aromatic template
Meihua Tu1, Brajesh K Rai, Alan M Mathiowetz
1Pfizer Worldwide Research and Development, 620 Memorial Drive, Cambridge, Massachusetts 02139, USA. meihua.tu@pfizer.com
Journal of Chemical Information and Modeling
|April 11, 2012
Summary
NEAT is a novel tool for identifying new aromatic rings with similar properties for drug discovery. It aids medicinal chemists in exploring chemical space for potential bioactivity.
Area of Science:
- Medicinal Chemistry
- Computational Chemistry
- Drug Discovery
Background:
- Identifying novel aromatic scaffolds is crucial for drug discovery.
- Existing tools have limitations in covering heteroaryl chemical space and property characterization.
Purpose of the Study:
- To introduce NEAT (Novel and Electronically equivalent Aromatic Template), a lead transformation tool.
- To enable identification of novel aromatic rings with similar bioactivity profiles to a query template.
Main Methods:
- Developed a comprehensive heteroaryl database.
- Precalculated high-level quantum mechanical (QM) properties including electrostatic potential (ESP) charges and dipole moments.
- Utilized QM ESP calculations for bioisosteric similarity assessment.
Main Results:
- NEAT covers a comprehensive heteroaryl chemical space, exceeding existing commercial software.
- Offers enhanced characterization of novel aryl cores using QM properties relevant to molecular interactions.
- Demonstrated a successful application example in exploring chemical space.
Conclusions:
- NEAT provides significant value to medicinal chemists for exploring uncharted aromatic chemical space.
- The tool facilitates the discovery of novel lead compounds with predictable bioactivity profiles.
- NEAT enhances the lead transformation process through advanced QM property analysis.
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