Phenols in Pharmaceuticals: Analysis of a Recurring Motif

Kevin A. Scott, Philip B. Cox, Jon T. Njardarson

Research output: Contribution to journalReview articlepeer-review

Abstract

Phenols and phenolic ethers are significant scaffolds recurring both in nature and among approved small-molecule pharmaceuticals. This compendium presents the first comprehensive compilation and analysis of the structures of U.S. FDA-approved molecules containing phenol or phenolic ether fragments. This dataset comprises 371 structures, which are strongly represented by natural products. A total of 55 of the compounds described here are on the World Health Organization's list of essential medicines. Structural analysis reveals significant differences in the physicochemical properties imparted by phenols versus phenol ethers, each having benefits and drawbacks for drug developability. Despite trends over the past decade to increase the fraction of sp3 centers in drug leads, thereby "escaping flatland", phenols and phenolic ethers are represented in 62% of small-molecule drugs approved in 2020, suggesting that this aromatic moiety holds a special place in drugs and natural products.

Original languageEnglish (US)
Pages (from-to)7044-7072
Number of pages29
JournalJournal of Medicinal Chemistry
Volume65
Issue number10
DOIs
StatePublished - May 26 2022

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Fingerprint

Dive into the research topics of 'Phenols in Pharmaceuticals: Analysis of a Recurring Motif'. Together they form a unique fingerprint.

Cite this