title: Structure-based design of caspase-1 inhibitor containing a diphenyl ether sulfonamide.
abstract: A series of compounds was designed and prepared as inhibitors of interleukin-1beta converting enzyme (ICE), also known as caspase-1. These inhibitors, which employ a diphenyl ether sulfonamide, were designed to improve potency by forming favorable interactions between the diphenyl ether rings and the prime side hydrophobic region. An X-ray crystal structure of a representative member of the diphenyl ether sulfonamide series bound to the active site of caspase-1 was obtained.
authors.affiliation: Department of Chemistry, Pfizer Global Research & Development, 2800 Plymouth Road, Ann Arbor, MI 48105, USA. shahipour@pfizer.com
authors.forename: A B
authors.initials: AB
authors.lastname: Shahripour
authors.forename: M S
authors.initials: MS
authors.lastname: Plummer
authors.forename: E A
authors.initials: EA
authors.lastname: Lunney
authors.forename: T K
authors.initials: TK
authors.lastname: Sawyer
authors.forename: C J
authors.initials: CJ
authors.lastname: Stankovic
authors.forename: M K
authors.initials: MK
authors.lastname: Connolly
authors.forename: J R
authors.initials: JR
authors.lastname: Rubin
authors.forename: N P
authors.initials: NP
authors.lastname: Walker
authors.forename: K D
authors.initials: KD
authors.lastname: Brady
authors.forename: H J
authors.initials: HJ
authors.lastname: Allen
authors.forename: R V
authors.initials: RV
authors.lastname: Talanian
authors.forename: W W
authors.initials: WW
authors.lastname: Wong
authors.forename: C
authors.initials: C
authors.lastname: Humblet
mesh_terms: D020170:Caspase 1 / Q000378:metabolism; D061945:Caspase Inhibitors; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004987:Ethers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D004987:Ethers; D013449:Sulfonamides; C440391:diphenyl ether sulfonamide; D020170:Caspase 1