Pyridones in drug discovery: recent advances

Bioorg Med Chem Lett. 2021 Feb 17:127849. doi: 10.1016/j.bmcl.2021.127849. Online ahead of print.ABSTRACTPyridones 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.PMID:33609656 | DOI:10.1016/j.bmcl.2021.127849

Source: Bioorganic and Medicinal Chemistry Letters - February 20, 2021 Category: Chemistry Authors: Yun Zhang Andrew Pike Source Type: research