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Analysis of Benzenoid Substitution Patterns in Small Molecule Active Pharmaceutical Ingredients

preprint
submitted on 31.10.2019, 21:12 and posted on 06.11.2019, 22:05 by Aleksandra Nilova, David Stuart
An analysis of benzenoid substitution patterns in small molecule active pharmaceutical ingredients (APIs) approved by the FDA reveals a preference for 1,4-substituted (para), 1-substituted (mono), 1,2,4-substituted, and 1,2-substituted (ortho) arenes. Notably, these substitution patterns are widely commercially available and readily accessible by electrophilic aromatic substitution (SEAr), but more highly substituted and contra-electronic substitution patterns are severely underrepresented in drug substances. Finally, structural variation decreases with increasing substitution and there is a strong reliance on natural product scaffolds in drugs with more highly substituted benzenoid rings.

History

Email Address of Submitting Author

dstuart@pdx.edu

Institution

Portland State University

Country

United States

ORCID For Submitting Author

0000-0003-3519-9067

Declaration of Conflict of Interest

No conflict of interest

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ChemRxiv

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