title: Inhibition of interleukin-1beta converting enzyme (ICE or caspase 1) by aspartyl acyloxyalkyl ketones and aspartyl amidooxyalkyl ketones.
abstract: A series of acyloxyalkyl and amidooxyalkyl ketones appended to a carbobenzyloxy aspartic acid core have been prepared. The most potent of these new inhibitors was 4i with a K(i) of 0.5 microM. These two series provide an improved understanding of the binding requirements for the hydrophobic prime side of ICE.
authors.affiliation: Pfizer Global Research and Development, Ann Arbor, MI 48105, USA. paul.galatsis@pfizer.com
authors.forename: Paul
authors.initials: P
authors.lastname: Galatsis
authors.forename: Bradley
authors.initials: B
authors.lastname: Caprathe
authors.forename: Dennis
authors.initials: D
authors.lastname: Downing
authors.forename: John
authors.initials: J
authors.lastname: Gilmore
authors.forename: William
authors.initials: W
authors.lastname: Harter
authors.forename: Sheryl
authors.initials: S
authors.lastname: Hays
authors.forename: Catherine
authors.initials: C
authors.lastname: Kostlan
authors.forename: Kristin
authors.initials: K
authors.lastname: Linn
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Lunney
authors.forename: Kim
authors.initials: K
authors.lastname: Para
authors.forename: Anthony
authors.initials: A
authors.lastname: Thomas
authors.forename: Joseph
authors.initials: J
authors.lastname: Warmus
authors.forename: Hamish
authors.initials: H
authors.lastname: Allen
authors.forename: Kenneth
authors.initials: K
authors.lastname: Brady
authors.forename: Robert
authors.initials: R
authors.lastname: Talanian
authors.forename: Nigel
authors.initials: N
authors.lastname: Walker
mesh_terms: D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D006801:Humans; D007659:Ketones / Q000494:pharmacology*; D008958:Models, Molecular; D009000:Monocytes / Q000187:drug effects
chemical_list: D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D007659:Ketones