title: Structure-activity relationships within a series of caspase inhibitors. Part 2: Heterocyclic warheads.
abstract: Various heterocyclic hetero-methyl ketones of the 1-naphthyloxyacetyl-Val-Asp backbone have been prepared. A study of their structure-activity relationship (SAR) related to caspase-1, -3, -6, and -8 is reported. Their efficacy in a cellular model of cell death is also discussed. Potent broad-spectrum caspase inhibitors have been identified.
authors.affiliation: Idun Pharmaceuticals Inc., 9380 Judicial Drive, San Diego, CA 92121, USA. bullman@idun.com
authors.forename: Brett R
authors.initials: BR
authors.lastname: Ullman
authors.forename: Teresa
authors.initials: T
authors.lastname: Aja
authors.forename: Ning
authors.initials: N
authors.lastname: Chen
authors.forename: Jose-Luis
authors.initials: JL
authors.lastname: Diaz
authors.forename: Xin
authors.initials: X
authors.lastname: Gu
authors.forename: Julia
authors.initials: J
authors.lastname: Herrmann
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Kalish
authors.forename: Donald S
authors.initials: DS
authors.lastname: Karanewsky
authors.forename: Lalitha
authors.initials: L
authors.lastname: Kodandapani
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Krebs
authors.forename: Steven D
authors.initials: SD
authors.lastname: Linton
authors.forename: Steven P
authors.initials: SP
authors.lastname: Meduna
authors.forename: Kip
authors.initials: K
authors.lastname: Nalley
authors.forename: Edward D
authors.initials: ED
authors.lastname: Robinson
authors.forename: Silvio P
authors.initials: SP
authors.lastname: Roggo
authors.forename: Robert O
authors.initials: RO
authors.lastname: Sayers
authors.forename: Albert
authors.initials: A
authors.lastname: Schmitz
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Ternansky
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Tomaselli
authors.forename: Joe C
authors.initials: JC
authors.lastname: Wu
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry; D061945:Caspase Inhibitors; D016923:Cell Death / Q000187:drug effects*; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D007659:Ketones / Q000138:chemical synthesis / Q000494:pharmacology*; D051379:Mice; D008954:Models, Biological; D009284:Naphthols / Q000737:chemistry; D013329:Structure-Activity Relationship; D014633:Valine / Q000737:chemistry
chemical_list: D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D006571:Heterocyclic Compounds; D007659:Ketones; D009284:Naphthols; C005366:naphthyl acetate; D001224:Aspartic Acid; D014633:Valine