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Multicomponent Synthesis and Binding Mode of Imidazo[1,2- a]pyridine-Capped Selective HDAC6 Inhibitors.

ABSTRACT: The multicomponent synthesis of a mini-library of histone deacetylase inhibitors with imidazo[1,2- a]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.

SUBMITTER: Mackwitz MKW

PROVIDER: S-EPMC5999327 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Multicomponent Synthesis and Binding Mode of Imidazo[1,2- a]pyridine-Capped Selective HDAC6 Inhibitors.

Mackwitz Marcel K W MKW Hamacher Alexandra A Osko Jeremy D JD Held Jana J Schöler Andrea A Christianson David W DW Kassack Matthias U MU Hansen Finn K FK

Organic letters 20180523 11

The multicomponent synthesis of a mini-library of histone deacetylase inhibitors with imidazo[1,2- a]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. ...[more]

PMID: 29790770

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