Minor structural modifications to Pracinostat produce big changes in its biological responses. (29th April 2019)

• Record Type: Journal Article
• Authors: Jia, Rong; Sun, Pengju; Zhang, Yan; Ge, Youjin; Yu, Niefang
• Is Part Of: Chemical biology & drug design. Volume 94:Number 2(2019)
• Page Start: 1488
• Page End: 1493
• Publication Date: 2019-04-29
• Subjects: HDAC inhibitors -- histone deacetylases -- hydroxamic acids -- Pracinostat -- synthesis; Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.13527
• Languages: English
• ISSNs: 1747-0277

Abstract

Abstract: 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 derivative1 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. Abstract : 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.