Multicomponent Synthesis and Binding Mode of Imidazo[1,2‑<i>a</i>]pyridine-Capped Selective HDAC6 Inhibitors

Abstract

The multicomponent synthesis of a mini-library of histone deacetylase inhibitors with imidazo­[1,2-<i>a</i>]­pyridine-based cap groups is presented. The biological evaluation led to the discovery of the hit compound MAIP-032 as a selective HDAC6 inhibitor with promising anticancer activity. The X-ray structure of catalytic domain 2 from Danio rerio HDAC6 complexed with MAIP-032 revealed a monodentate zinc-binding mode