Malonyl alpha-mercaptoketones and alpha-mercaptoalcohols, a new class of matrix metalloproteinase inhibitors.
A novel series of matrix metalloproteinase (MMP) inhibitors is described. Incorporation of a terminal alpha-mercaptoketone or alpha-mercaptoalcohol in the zinc binding domain of a series of inhibitors led to compounds exhibiting low nanomolar activity against collagenase-1 (MMP-1), stromelysin (MMP-3), and gelatinase-B (MMP-9).
Campbell
D A
DA
Affymax Research Institute, Santa Clara, CA 95051, USA.
Xiao
X Y
XY
Harris
D
D
Ida
S
S
Mortezaei
R
R
Ngu
K
K
Shi
L
L
Tien
D
D
Wang
Y
Y
Navre
M
M
Patel
D V
DV
Sharr
M A
MA
DiJoseph
J F
JF
Killar
L M
LM
Leone
C L
CL
Levin
J I
JI
Skotnicki
J S
JS
D000438:Alcohols / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D015195:Drug Design; D006877:Hydroxamic Acids / Q000737:chemistry / Q000494:pharmacology; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007700:Kinetics; D020781:Matrix Metalloproteinase 1; D020780:Matrix Metalloproteinase 9; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015032:Zinc / Q000378:metabolism
D000438:Alcohols; D006877:Hydroxamic Acids; D007659:Ketones; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D013438:Sulfhydryl Compounds; C100342:marimastat; D008666:Metalloendopeptidases; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1; D015032:Zinc