title: Design and synthesis of 4-quinolinone 2-carboxamides as calpain inhibitors.
abstract: Calpains are involved in a variety of calcium-regulated cellular processes, such as signal transduction, cell proliferation, differentiation, and apoptosis. Excessive calpain activation contributes to serious cellular damage and has been reported in many pathological conditions. 4-Quinolinone 2-carboxamide derivatives were prepared and evaluated for mu-calpain inhibitory activities. Of the compounds synthesized, 3a and 3k, which possess a primary amide and 4-methoxyphenethyl amide at P1' region, were found to most potently inhibit mu-calpain with IC50 values of 0.71+/-0.07 and 0.73+/-0.23 microM, respectively. On the other hand, the incorporation of pyridine-containing amides decreased inhibitory activity.
authors.affiliation: Department of Pharmaceutical Sciences, Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Dong Hyuk
authors.initials: DH
authors.lastname: Nam
authors.forename: Kwang Seob
authors.initials: KS
authors.lastname: Lee
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Kim
authors.forename: Seo Yun
authors.initials: SY
authors.lastname: Jung
authors.forename: Sung Hyun
authors.initials: SH
authors.lastname: Chung
authors.forename: Hyoung Ja
authors.initials: HJ
authors.lastname: Kim
authors.forename: Nam Doo
authors.initials: ND
authors.lastname: Kim
authors.forename: Changbae
authors.initials: C
authors.lastname: Jin
authors.forename: Yong Sup
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002154:Calpain / Q000037:antagonists & inhibitors*; D015195:Drug Design; D006860:Hydrogen Bonding; D007700:Kinetics; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D011480:Protease Inhibitors; D015363:Quinolones; D002154:Calpain