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Analysis of Benzenoid Substitution Patterns in Small Molecule Active Pharmaceutical Ingredients

preprint
submitted on 31.10.2019 and posted on 06.11.2019 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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