Macrocyclic hydroxamate inhibitors of matrix metalloproteinases and TNF-alpha production.
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.
Cherney
R J
RJ
The DuPont Pharmaceutical Co., Experimental Station, Wilmington, DE 19880-0500, USA.
Wang
L
L
Meyer
D T
DT
Xue
C B
CB
Arner
E C
EC
Copeland
R A
RA
Covington
M B
MB
Hardman
K D
KD
Wasserman
Z R
ZR
Jaffee
B D
BD
Decicco
C P
CP
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*
D006877:Hydroxamic Acids; D008070:Lipopolysaccharides; D061965:Matrix Metalloproteinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D008666:Metalloendopeptidases; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1