title: alpha-Alkyl-alpha-amino-beta-sulphone hydroxamates as potent MMP inhibitors that spare MMP-1.
abstract: A series of alpha-alkyl-alpha-amino-beta-sulphone hydroxamates was prepared and evaluated for potency versus MMP-2 and MMP-13, and for selectivity versus MMP-1. Low nanomolar potency was obtained with selectivity versus MMP-1 ranging from >10 to >1000. Selected compounds were orally bioavailable.
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: 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: G E
authors.initials: GE
authors.lastname: Munie
authors.forename: C
authors.initials: C
authors.lastname: Swearingen
mesh_terms: D000473:Alkanes / Q000737:chemistry / Q000494:pharmacology*; 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; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D013329:Structure-Activity Relationship
chemical_list: D000473:Alkanes; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1