title: alpha-Amino-beta-sulphone hydroxamates as potent MMP-13 inhibitors that spare MMP-1.
abstract: A series of alpha-amino-beta-sulphone hydroxamates was prepared and evaluated for potency versus MMP-13 and selectivity versus MMP-1. Various substituents were employed on the alpha-amino group (P(1) position), as well as different groups attached to the sulphone group extending into P(1)'. Low nanomolar potency was obtained for MMP-13 with selectivity versus MMP-1 of >1000x for a number of analogues.
authors.affiliation: Departments of Medicinal Chemistry and Inflammation-Oncology, Pharmacia Research & Development, 4901 Searle Parkway, Skokie, IL 60077, USA. daniel.p.becker@pharmacia.com
authors.forename: D P
authors.initials: DP
authors.lastname: Becker
authors.forename: T E
authors.initials: TE
authors.lastname: Barta
authors.forename: L
authors.initials: L
authors.lastname: Bedell
authors.forename: G
authors.initials: G
authors.lastname: DeCrescenzo
authors.forename: J
authors.initials: J
authors.lastname: Freskos
authors.forename: D P
authors.initials: DP
authors.lastname: Getman
authors.forename: S L
authors.initials: SL
authors.lastname: Hockerman
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.forename: P
authors.initials: P
authors.lastname: Mehta
authors.forename: B
authors.initials: B
authors.lastname: Mischke
authors.forename: G E
authors.initials: GE
authors.lastname: Munie
authors.forename: C
authors.initials: C
authors.lastname: Swearingen
authors.forename: C I
authors.initials: CI
authors.lastname: Villamil
mesh_terms: D017364:Collagenases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D053509:Matrix Metalloproteinase 13; D061965:Matrix Metalloproteinase Inhibitors; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; D020781:Matrix Metalloproteinase 1