title: Synthesis and evaluation of thiazepines as interleukin-1beta converting enzyme (ICE) inhibitors.
abstract: A series of monocyclic thiazepine inhibitors of interleukin-1beta converting enzyme (ICE) were synthesized in eight steps from commercially available intermediates. In vitro biological evaluation showed the thiazepines to be moderately potent ICE inhibitors, with the most active compound exhibiting an IC50 value of 30 nM in an enzyme inhibition assay. Compounds of this class possessed good selectivity against the related enzymes caspase-3 and caspase-8.
authors.affiliation: Procter and Gamble Pharmaceuticals Incorporated, 8700 Mason-Montgomery Road, Mason, OH 45040, USA. ellis.cd@pg.com
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Ellis
authors.forename: Kofi A
authors.initials: KA
authors.lastname: Oppong
authors.forename: Michael C
authors.initials: MC
authors.lastname: Laufersweiler
authors.forename: Steven V
authors.initials: SV
authors.lastname: O'Neil
authors.forename: David L
authors.initials: DL
authors.lastname: Soper
authors.forename: Yili
authors.initials: Y
authors.lastname: Wang
authors.forename: John A
authors.initials: JA
authors.lastname: Wos
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: D020170:Caspase 1 / Q000378:metabolism; D061945:Caspase Inhibitors; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013841:Thiazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D013841:Thiazepines; D020170:Caspase 1