The present application describes novel uracil derivatives of formula I: A-W-U-X-Y-Z-U.sup.a-X.sup.a-Y.sup.a-Z.sup.aIor pharmaceutically acceptable salt or prodrug forms thereof, wherein A, W, U, X, Y, Z, U.sup.a, X.sup.a, Y.sup.a, and Z.sup.a are defined in the present specification, which are useful as inhibitors of TNF-.alpha. converting enzyme (TACE), matrix metalloproteinases (MMP), aggrecanase or a combination thereof.