title: The design and synthesis of sulfonamides as caspase-1 inhibitors.
abstract: A series of sulfonamides (1) has been prepared as inhibitors of interleukin-1beta converting enzyme (ICE), also known as caspase 1. These compounds were designed to improve potency by rigidifying the enzyme bound molecule through an intramolecular hydrogen bond. An X-ray crystal structure of a representative member of this series bound to the active site of ICE, confirms the presence of the hydrogen bonding interaction.
authors.affiliation: Chemistry Department, Pfizer Global Research and Development, 2800 Plymouth Rd, Ann Arbor, MI 48105, USA. william.harter@pfizer.com
authors.forename: William G
authors.initials: WG
authors.lastname: Harter
authors.forename: Hans
authors.initials: H
authors.lastname: Albrect
authors.forename: Kenneth
authors.initials: K
authors.lastname: Brady
authors.forename: Bradley
authors.initials: B
authors.lastname: Caprathe
authors.forename: James
authors.initials: J
authors.lastname: Dunbar
authors.forename: John
authors.initials: J
authors.lastname: Gilmore
authors.forename: Sheryl
authors.initials: S
authors.lastname: Hays
authors.forename: Catherine R
authors.initials: CR
authors.lastname: Kostlan
authors.forename: Beth
authors.initials: B
authors.lastname: Lunney
authors.forename: Nigel
authors.initials: N
authors.lastname: Walker
mesh_terms: D001665:Binding Sites; D020170:Caspase 1 / Q000378:metabolism; D061945:Caspase Inhibitors; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D015843:Serpins / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology*; D014764:Viral Proteins
chemical_list: D061945:Caspase Inhibitors; D015843:Serpins; D013449:Sulfonamides; D014764:Viral Proteins; C074641:interleukin-1beta-converting enzyme inhibitor; D020170:Caspase 1