Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1375885 | Bioorganic & Medicinal Chemistry Letters | 2009 | 6 Pages |
The involvement of μ-calpain in neurological disorders, such as stroke and Alzheimer’s disease has attracted considerable interest in the use of calpain inhibitors as therapeutic agents. 4-Aryl-4-oxobutanoic acid amide derivatives 4 were designed as acyclic variants of μ-calpain inhibitory chromone and quinolinone derivatives. Of the compounds synthesized, 4c-2, which possesses a 2-methoxymethoxy group at the phenyl ring and a primary amide at the warhead region most potently inhibited μ-calpain (IC50 = 0.34 μM). Our findings suggest that the 4-aryl-4-oxobutanoic acid amide derivatives should be considered as a new family of μ-calpain inhibitors.
Graphical abstractAryl-4-oxobutanoic acid amide derivatives 4 were designed as acyclic variants of μ-calpain inhibitory chromone and quinolinone derivatives. Of the compounds synthesized, 4c-2, which possesses a 2-methoxymethoxy group at the phenyl ring and a primary amide at the warhead region of the inhibitor most potently inhibited μ-calpain (IC50 = 0.34 μM). Our findings suggest that the 4-aryl-4-oxobutanoic acid amide derivatives should be considered a new family of μ-calpain inhibitors.Figure optionsDownload full-size imageDownload as PowerPoint slide