Development of novel proteasome inhibitors based on phthalazinone scaffold. Issue 12 (15th June 2016)

• Record Type: Journal Article
• Authors: Yang, Lingfei; Wang, Wei; Sun, Qi; Xu, Fengrong; Niu, Yan; Wang, Chao; Liang, Lei; Xu, Ping
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 12(2016)
• Page Start: 2801
• Page End: 2805
• Publication Date: 2016-06-15
• Subjects: Proteasome inhibitors -- Phthalazinone -- Triphenylphosphine -- Drug design -- Structure–activity relationship; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.04.067
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: In this study we designed a series of proteasome inhibitors using pyridazinone as initial scaffold, and extended the structure with rational design by computer aided drug design (CADD). Two different synthetic routes were explored and the biological evaluation of the phthalazinone derivatives was investigated. Most importantly, electron positive triphenylphosphine group was first introduced in the structure of proteasome inhibitors and potent inhibition was achieved. As6c was the most potent inhibitor of proteasome, we examined the structure–activity relationship (SAR) of6c analogs.