alpha-Alkyl-alpha-amino-beta-sulphone hydroxamates as potent MMP inhibitors that spare MMP-1.
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.
Becker
D P
DP
Departments of Medicinal Chemistry and Inflammation-Oncology, Pharmacia Research & Development, 4901 Searle Parkway, Skokie, IL 60077, USA. daniel.p.becker@pharmacia.com
DeCrescenzo
G
G
Freskos
J
J
Getman
D P
DP
Hockerman
S L
SL
Li
M
M
Mehta
P
P
Munie
G E
GE
Swearingen
C
C
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
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