TY - JOUR
T1 - Phenols in Pharmaceuticals
T2 - Analysis of a Recurring Motif
AU - Scott, Kevin A.
AU - Cox, Philip B.
AU - Njardarson, Jon T.
N1 - Funding Information:
We would like to thank the National Science Foundation (CHE 1855708) for financial support of our pharmaceutical poster outreach projects, and the resulting analysis efforts.
Publisher Copyright:
© 2022 American Chemical Society.
PY - 2022/5/26
Y1 - 2022/5/26
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.jmedchem.2c00223
DO - 10.1021/acs.jmedchem.2c00223
M3 - Review article
C2 - 35533692
AN - SCOPUS:85130726037
SN - 0022-2623
VL - 65
SP - 7044
EP - 7072
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 10
ER -