Physical Sciences and Mathematics Commons^™

Alpha-Alkyl-Alpha-Amino-Beta-Sulphone Hydroxamates As Potent Mmp Inhibitors That Spare Mmp-1, Daniel Becker, Gary A. Decrescenzo, John Freskos, Daniel P. Getman

Chemistry: Faculty Publications and Other Works

A series of α-alkyl-α-amino-β-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.

Α-Amino-Β-Sulphone Hydroxamates As Potent Mmp-13 Inhibitors That Spare Mmp-1, Daniel P. Becker Ph.D., Thomas E. Barta, Louis Bedell, Gary Decrescenzo, John Freskos, Daniel P. Getman, Susan L. Hockerman, Madeleine Li, Pramod Mehta, Brent Mischke, Grace E. Munie, Craig Swearingen, Clara I. Villamil

Chemistry: Faculty Publications and Other Works

A series of α-amino-β-sulphone hydroxamates was prepared and evaluated for potency versus MMP-13 and selectivity versus MMP-1. Various substituents were employed on the α-amino group (P1 position), as well as different groups attached to the sulphone group extending into P1′. Low nanomolar potency was obtained for MMP-13 with selectivity versus MMP-1 of >1000× for a number of analogues.

α-Amino-β-sulphone hydroxamates were prepared, which are potent MMP-13 inhibitors with selectivity versus MMP-1 of >1000× for a number of analogues. Selected compounds exhibited oral bioavailability.