Aryl ketones as novel replacements for the C-terminal amide bond of succinyl hydroxamate MMP inhibitors.
A series of succinyl hydroxamate MMP inhibitors were prepared incorporating an aryl amino ketone moiety in place of the more typical C-terminal amino acid amides. Compounds of the C-terminal ketone series displayed potent inhibition of MMPs. Several compounds of the series were shown to be orally bioavailable.
Sheppard
G S
GS
Department 47J, AP-10, Abbott Laboratory, Abbott Park, Illinois 60064, USA.
Florjancic
A S
AS
Giesler
J R
JR
Xu
L
L
Guo
Y
Y
Davidsen
S K
SK
Marcotte
P A
PA
Elmore
I
I
Albert
D H
DH
Magoc
T J
TJ
Bouska
J J
JJ
Goodfellow
C L
CL
Morgan
D W
DW
Summers
J B
JB
D018093:Gelatinases / Q000037:antagonists & inhibitors*; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007659:Ketones / Q000494:pharmacology*; D020781:Matrix Metalloproteinase 1; D020778:Matrix Metalloproteinase 2; D020783:Matrix Metalloproteinase 7; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D011480:Protease Inhibitors / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D006877:Hydroxamic Acids; D007659:Ketones; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D018093:Gelatinases; D008666:Metalloendopeptidases; D020783:Matrix Metalloproteinase 7; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1