Medicinal chemistry insights into non-hydroxamate HDAC6 selective inhibitors

AbstractHDAC6 is predominantly found in the cytoplasm and is mainly responsible for deacetylation of non-histone proteins including α-tubulin in microtubules, the HSP90 chaperone, cortactin, etc. Inhibition of HDAC6 has been shown to be efficacious in treating cancer, neurodegenerative diseases, heart failure, pain, fibrosis, and inflammatory diseases. This review focuses on the recent more drug-like selective HDAC6 inhibitors, especially the two major chemotypes of mercaptoacetamides and fluoroalkyl-oxadiazoles. The latter class lacks structural alert thus has low potential for toxicities. As a consequence, fluoroalkyl-oxadiazoles, especially difluoromethyl 1,3,4-oxadiazoles, are promising HDAC6 inhibitors for the treatm ent of chronic diseases such as heart failure, neurodegenerative diseases, fibrosis, and pain.Graphical abstract

Source: Medicinal Chemistry Research - January 1, 2023 Category: Chemistry Source Type: research