title: Solid-phase analogue synthesis of caspase-3 inhibitors via palladium-catalyzed amination of 3-bromopyrazinones.
abstract: Caspase-3 is a cysteinyl protease that mediates apoptotic cell death. Its inhibition may have an important impact on the treatment of several degenerative diseases. Here we report the synthesis of reversible inhibitors via a solid-support palladium-catalyzed amination of 3-bromopyrazinones and the discovery of a pan-caspase reversible inhibitor.
authors.affiliation: Merck Frosst Centre for Therapeutic Research, Merck Frosst Canada & Co., PO Box 1005, Pointe-Claire-Dorval, Quebec, Canada H9R 4P8. elise_isabel@merck.com
authors.forename: Elise
authors.initials: E
authors.lastname: Isabel
authors.forename: Renee
authors.initials: R
authors.lastname: Aspiotis
authors.forename: W Cameron
authors.initials: WC
authors.lastname: Black
authors.forename: John
authors.initials: J
authors.lastname: Colucci
authors.forename: Réjean
authors.initials: R
authors.lastname: Fortin
authors.forename: André
authors.initials: A
authors.lastname: Giroux
authors.forename: Erich L
authors.initials: EL
authors.lastname: Grimm
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Han
authors.forename: Christophe
authors.initials: C
authors.lastname: Mellon
authors.forename: Donald W
authors.initials: DW
authors.lastname: Nicholson
authors.forename: Dita M
authors.initials: DM
authors.lastname: Rasper
authors.forename: Johanne
authors.initials: J
authors.lastname: Renaud
authors.forename: Sophie
authors.initials: S
authors.lastname: Roy
authors.forename: John
authors.initials: J
authors.lastname: Tam
authors.forename: Paul
authors.initials: P
authors.lastname: Tawa
authors.forename: John P
authors.initials: JP
authors.lastname: Vaillancourt
authors.forename: Steven
authors.initials: S
authors.lastname: Xanthoudakis
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Zamboni
mesh_terms: D000586:Amination; D061945:Caspase Inhibitors; D002384:Catalysis; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007202:Indicators and Reagents; D013058:Mass Spectrometry; D010165:Palladium / Q000737:chemistry*; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D011719:Pyrazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D061945:Caspase Inhibitors; D007202:Indicators and Reagents; D011480:Protease Inhibitors; D011719:Pyrazines; D011994:Recombinant Proteins; D010165:Palladium