title: Macrocyclic hydroxamate inhibitors of matrix metalloproteinases and TNF-alpha production.
abstract: Several macrocyclic, hydroxamate derivatives were synthesized and evaluated as inhibitors of matrix metalloproteinases (MMPs) and tumour necrosis factor-alpha (TNF-alpha) production. These macrocycles are anti-succinate based inhibitors linked from P1 to P2'. A variety of functionality was installed at the P1-P2' linkage, which gave inhibitors that displayed excellent MMP inhibition and good TNF-alpha suppression.
authors.affiliation: The DuPont Pharmaceutical Co., Experimental Station, Wilmington, DE 19880-0500, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Cherney
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: D T
authors.initials: DT
authors.lastname: Meyer
authors.forename: C B
authors.initials: CB
authors.lastname: Xue
authors.forename: E C
authors.initials: EC
authors.lastname: Arner
authors.forename: R A
authors.initials: RA
authors.lastname: Copeland
authors.forename: M B
authors.initials: MB
authors.lastname: Covington
authors.forename: K D
authors.initials: KD
authors.lastname: Hardman
authors.forename: Z R
authors.initials: ZR
authors.lastname: Wasserman
authors.forename: B D
authors.initials: BD
authors.lastname: Jaffee
authors.forename: C P
authors.initials: CP
authors.lastname: Decicco
mesh_terms: D018360:Crystallography, X-Ray; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008070:Lipopolysaccharides / Q000378:metabolism; D020781:Matrix Metalloproteinase 1; D020780:Matrix Metalloproteinase 9; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors* / Q000145:classification; D008956:Models, Chemical; D008958:Models, Molecular; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D006877:Hydroxamic Acids; D008070:Lipopolysaccharides; D061965:Matrix Metalloproteinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D008666:Metalloendopeptidases; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1