volume 16 issue 4 pages 583-587

Comparative Hydrophobicity, Solubility, and Metabolic Stability of 4(1H)-Pyridones, 4(1H)-Quinolones, and 9(10H)-Acridones

Rongguo Ren 1
Longjin Zhong 2
Long‐Jin Zhong 2
Cassandra Noack 2
Deepender Kaushik 1
Derek A. Leas 1
Xiaofang Wang 1
X Wang 1
Yuxiang Dong 1
Susan C Charman 2
Jonathan L. Vennerstrom 1
Publication typeJournal Article
Publication date2025-03-24
scimago Q1
wos Q2
SJR0.805
CiteScore5.8
Impact factor4.0
ISSN19485875
Abstract
The relatively polar 4(1H)-pyridone (4-pyridone) heterocycle is found in many drugs and drug candidates. In a comparison of the hydrophobicity, aqueous solubility, and metabolic stability of several matched sets of 4-pyridones, 4(1H)-quinolones (4-quinolones), and 9(10H)-acridones (9-acridones), measured chromatographic log D 7.4 values show that 9-acridones are more hydrophobic and less soluble than their 4-quinolone and 4-pyridone counterparts. All 4-pyridone/4-quinolone pairs had identical or very similar hydrophobicity and aqueous solubility properties. Metabolic stability increased steadily from 9-acridones to 4-quinolones to 4-pyridones, consistent with the progressive increase in Fsp3 values and log D. The gain in metabolic stability was not as great for those 4-pyridone/4-quinolone pairs featuring additional polar functional groups/heterocycles.
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Ren R. et al. Comparative Hydrophobicity, Solubility, and Metabolic Stability of 4(1H)-Pyridones, 4(1H)-Quinolones, and 9(10H)-Acridones // ACS Medicinal Chemistry Letters. 2025. Vol. 16. No. 4. pp. 583-587.
GOST all authors (up to 50) Copy
Ren R., Zhong L., Zhong L., Noack C., Kaushik D., Leas D. A., Wang X., Wang X., Dong Y., Charman S. C., Vennerstrom J. L. Comparative Hydrophobicity, Solubility, and Metabolic Stability of 4(1H)-Pyridones, 4(1H)-Quinolones, and 9(10H)-Acridones // ACS Medicinal Chemistry Letters. 2025. Vol. 16. No. 4. pp. 583-587.
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TY - JOUR
DO - 10.1021/acsmedchemlett.4c00618
UR - https://pubs.acs.org/doi/10.1021/acsmedchemlett.4c00618
TI - Comparative Hydrophobicity, Solubility, and Metabolic Stability of 4(1H)-Pyridones, 4(1H)-Quinolones, and 9(10H)-Acridones
T2 - ACS Medicinal Chemistry Letters
AU - Ren, Rongguo
AU - Zhong, Longjin
AU - Zhong, Long‐Jin
AU - Noack, Cassandra
AU - Kaushik, Deepender
AU - Leas, Derek A.
AU - Wang, Xiaofang
AU - Wang, X
AU - Dong, Yuxiang
AU - Charman, Susan C
AU - Vennerstrom, Jonathan L.
PY - 2025
DA - 2025/03/24
PB - American Chemical Society (ACS)
SP - 583-587
IS - 4
VL - 16
SN - 1948-5875
ER -
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@article{2025_Ren,
author = {Rongguo Ren and Longjin Zhong and Long‐Jin Zhong and Cassandra Noack and Deepender Kaushik and Derek A. Leas and Xiaofang Wang and X Wang and Yuxiang Dong and Susan C Charman and Jonathan L. Vennerstrom},
title = {Comparative Hydrophobicity, Solubility, and Metabolic Stability of 4(1H)-Pyridones, 4(1H)-Quinolones, and 9(10H)-Acridones},
journal = {ACS Medicinal Chemistry Letters},
year = {2025},
volume = {16},
publisher = {American Chemical Society (ACS)},
month = {mar},
url = {https://pubs.acs.org/doi/10.1021/acsmedchemlett.4c00618},
number = {4},
pages = {583--587},
doi = {10.1021/acsmedchemlett.4c00618}
}
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Ren, Rongguo, et al. “Comparative Hydrophobicity, Solubility, and Metabolic Stability of 4(1H)-Pyridones, 4(1H)-Quinolones, and 9(10H)-Acridones.” ACS Medicinal Chemistry Letters, vol. 16, no. 4, Mar. 2025, pp. 583-587. https://pubs.acs.org/doi/10.1021/acsmedchemlett.4c00618.