title: Design and synthesis of 4-aryl-4-oxobutanoic acid amides as calpain inhibitors.
abstract: The involvement of mu-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 mu-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 mu-calpain (IC(50)=0.34 microM). Our findings suggest that the 4-aryl-4-oxobutanoic acid amide derivatives should be considered as a new family of mu-calpain inhibitors.
authors.affiliation: School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, Liaoning, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Seo Yoon
authors.initials: SY
authors.lastname: Jung
authors.forename: Changbae
authors.initials: C
authors.lastname: Jin
authors.forename: Nam Doo
authors.initials: ND
authors.lastname: Kim
authors.forename: Ping
authors.initials: P
authors.lastname: Gong
authors.forename: Yong Sup
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000577:Amides / Q000737:chemistry; D020148:Butyric Acid / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002154:Calpain / Q000037:antagonists & inhibitors*; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design
chemical_list: D000577:Amides; D015853:Cysteine Proteinase Inhibitors; D020148:Butyric Acid; D002154:Calpain