Minor structural modifications to Pracinostat produce big changes in its biological responses

A series of compounds similar to Pracinostat that contained benzimidazole ring and N‐hydroxyacrylamide attached at 5‐ or 6‐position were designed, synthesized, and evaluated as HDAC inhibitors. It was interesting to find that the corresponding derivative 1 with N‐hydroxyacrylamide attached at 5‐posi...

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Bibliographic Details
Published in:Chemical biology & drug design 2019-08, Vol.94 (2), p.1488-1493
Main Authors: Jia, Rong, Sun, Pengju, Zhang, Yan, Ge, Youjin, Yu, Niefang
Format: Article
Language:English
Subjects:
HDAC inhibitors
histone deacetylases
hydroxamic acids
Pracinostat
synthesis
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Summary:A series of compounds similar to Pracinostat that contained benzimidazole ring and N‐hydroxyacrylamide attached at 5‐ or 6‐position were designed, synthesized, and evaluated as HDAC inhibitors. It was interesting to find that the corresponding derivative 1 with N‐hydroxyacrylamide attached at 5‐position was a potent HDAC inhibitor while the others at 6‐position were not. This is the first time to demonstrate the position difference plays important role in the HDAC inhibitory activities of the cinnamic hydroxamates. Minor changes in the structure of Pracinostat significantly alter its biological activity. A representative series of structural analogs of Pracinostat have been designed, synthesized, and  evaluated as HDAC inhibitors compared with Pracinostat.
ISSN:1747-0277
1747-0285
DOI:10.1111/cbdd.13527