Title

Analysis of Benzenoid Substitution Patterns in Small Molecule Active Pharmaceutical Ingredients.

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

Description

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.jmedchem.0c00915.

  • User-guide to the Excel database and additional “shape” plots (PDF)
  • Database of benzenoid rings in FDA approved small molecule drugs (XLSX)

DOI

10.1021/acs.jmedchem.0c00915

Persistent Identifier

https://archives.pdx.edu/ds/psu/34893

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