Bioisostere

Solubility

Biochemistry

Drug discovery

Combinatorial chemistry

Organic chemistry

Chemical synthesis

In vitro

Chemistry

Metabolic stability

Lipophilicity

Pyridine

Bioorganic & Medicinal Chemistry Letters

Pyridones have been utilized as privileged scaffolds in drug discovery. Some of the important roles where this class of heterocycles have found utility in medicinal chemistry include the ability to 1) serve both as a hydrogen bond acceptor and/or a donor; 2) act as a bioisostere for amides, phenyls, pyridines and other nitrogen- or oxygen-containing heterocycles; and 3) impact a target drug molecule’s lipophilicity, aqueous solubility and metabolic stability. Detailed discussions of recent advances in their utilization as nonpeptidic mimics and as kinase hinge binding motifs are included. Selected literature examples published from the past twenty years where pyridones have been employed as bioisosteres for phenyls, pyridines, pyridine N-oxides and phenol rings are provided. In addition, this review summarizes the current understanding of possible reactive metabolites related to the pyridone structure.

Pyridones in drug discovery: Recent advances