title: Novel pyrazinone mono-amides as potent and reversible caspase-3 inhibitors.
abstract: The iterative process for the discovery of a series of pyrazinone mono-amides as potent, selective and reversible non-peptide caspase-3 inhibitors (e.g., M826 and M867) is reported. These compounds display potent anti apoptotic activities in a number of cell based systems in vitro as well as in several animal models in vivo.
authors.affiliation: Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, Merck Frosst Canada & Co., PO Box 1005, Pointe-Claire-Dorval, Quebec, Canada H9R 4P8. yongxin_han@merck.com
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Han
authors.forename: André
authors.initials: A
authors.lastname: Giroux
authors.forename: John
authors.initials: J
authors.lastname: Colucci
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Bayly
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Mckay
authors.forename: Sophie
authors.initials: S
authors.lastname: Roy
authors.forename: Steve
authors.initials: S
authors.lastname: Xanthoudakis
authors.forename: John
authors.initials: J
authors.lastname: Vaillancourt
authors.forename: Dita M
authors.initials: DM
authors.lastname: Rasper
authors.forename: John
authors.initials: J
authors.lastname: Tam
authors.forename: Paul
authors.initials: P
authors.lastname: Tawa
authors.forename: Donald W
authors.initials: DW
authors.lastname: Nicholson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Zamboni
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D061945:Caspase Inhibitors; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D007962:Leukocytes / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects; D011719:Pyrazines / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D011719:Pyrazines; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; D053148:Caspase 3