Pyran-containing sulfonamide hydroxamic acids: potent MMP inhibitors that spare MMP-1
LA Reiter, RP Robinson, KF McClure, CS Jones… - Bioorganic & medicinal …, 2004 - Elsevier
LA Reiter, RP Robinson, KF McClure, CS Jones, MR Reese, PG Mitchell, IG Otterness…
Bioorganic & medicinal chemistry letters, 2004•ElsevierThe SAR of a series of sterically hindered sulfonamide hydroxamic acids with relatively large
P1′ groups is described. The compounds typically spare MMP-1 while being potent
inhibitors of MMP-13. The metabolically more stable compounds in the series contain either
a monocyclic or bicyclic pyran ring adjacent to the hydroxamate group. Despite the sparing
of MMP-1, pre-clinical and clinical studies revealed that fibrosis in rats and MSS in humans
is still produced.
P1′ groups is described. The compounds typically spare MMP-1 while being potent
inhibitors of MMP-13. The metabolically more stable compounds in the series contain either
a monocyclic or bicyclic pyran ring adjacent to the hydroxamate group. Despite the sparing
of MMP-1, pre-clinical and clinical studies revealed that fibrosis in rats and MSS in humans
is still produced.
The SAR of a series of sterically hindered sulfonamide hydroxamic acids with relatively large P1′ groups is described. The compounds typically spare MMP-1 while being potent inhibitors of MMP-13. The metabolically more stable compounds in the series contain either a monocyclic or bicyclic pyran ring adjacent to the hydroxamate group. Despite the sparing of MMP-1, pre-clinical and clinical studies revealed that fibrosis in rats and MSS in humans is still produced.
Elsevier
