title: Synthesis and evaluation of novel 8,6-fused bicyclic peptidomimetic compounds as interleukin-1beta converting enzyme inhibitors.
abstract: Two novel 8,6-fused bicyclic peptidomimetic ring systems were synthesized utilizing olefin metathesis as the key reaction for the formation of the eight-membered ring. Both peptidomimetic scaffolds were further elaborated into potent ICE inhibitors, with numerous compounds exhibiting caspase-1 IC(50)s less than 10nM.
authors.affiliation: Procter & Gamble Pharmaceuticals, Inc., 8700 Mason-Montgomery Road, Mason, OH 45040, USA. oneil.sv@pg.com
authors.forename: Steven V
authors.initials: SV
authors.lastname: O'Neil
authors.forename: Yili
authors.initials: Y
authors.lastname: Wang
authors.forename: Michael C
authors.initials: MC
authors.lastname: Laufersweiler
authors.forename: Kofi A
authors.initials: KA
authors.lastname: Oppong
authors.forename: David L
authors.initials: DL
authors.lastname: Soper
authors.forename: John A
authors.initials: JA
authors.lastname: Wos
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Ellis
authors.forename: Mark W
authors.initials: MW
authors.lastname: Baize
authors.forename: Gregory K
authors.initials: GK
authors.lastname: Bosch
authors.forename: Amy N
authors.initials: AN
authors.lastname: Fancher
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Maureen K
authors.initials: MK
authors.lastname: Suchanek
authors.forename: Richard L
authors.initials: RL
authors.lastname: Wang
authors.forename: Biswanath
authors.initials: B
authors.lastname: De
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Demuth
mesh_terms: D032701:Biomimetics; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis / Q000494:pharmacology*; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D008958:Models, Molecular; D008968:Molecular Conformation
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents