Analysis of Benzenoid Substitution Patterns in Small Molecule Active Pharmaceutical Ingredients.
Sponsor
Portland State University is acknowledged for financial support.
Published In
Journal of Medicinal Chemistry
Document Type
Citation
Publication Date
8-31-2020
Abstract
Previous analyses have revealed that benzenoid rings are prevalent scaffolds in active pharmaceutical ingredients (APIs). Here, we analyze the substitution patterns of benzenoid rings in small molecule APIs approved by the FDA through 2019 and show that only a few substitution patterns (1-, 1,2-, 1,4-, and 1,2,4-) prevail, and the distribution has remained relatively constant over time. We postulate the connection between available synthetic methods and the occurrence of a few benzenoid substitution patterns by providing an overview of synthetic methods that elaborate existing substitution patterns and those that create new substitution patterns, including those of the former that are favored by medicinal chemists. Finally, we calculated medicinal chemistry properties of benzenoid containing APIs that are often used by practitioners as design elements, including "druglikeness", shape, complexity, and similarity/diversity and discuss these properties in the context of synthesis.
Rights
Copyright © 2020 American Chemical Society
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DOI
10.1021/acs.jmedchem.0c00915
Persistent Identifier
https://archives.pdx.edu/ds/psu/34893
Citation Details
Nilova, A., Campeau, L.-C., Sherer, E. C., & Stuart, D. R. (2020). Analysis of Benzenoid Substitution Patterns in Small Molecule Active Pharmaceutical Ingredients. Journal of Medicinal Chemistry, 63(22), 13389–13396. https://doi.org/10.1021/acs.jmedchem.0c00915
Description
The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.jmedchem.0c00915.
Database of benzenoid rings in FDA approved small molecule drugs (XLSX)