The present invention provides compounds of Formula (I): ##STR00001## or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein the variables L, Z.sup.0, R.sup.1, R.sup.4, R.sup.5, and R.sup.11 are defined are as defined herein, which are useful as inhibitors of matrix metalloproteinases (MMP), TNF-.alpha. converting enzyme (TACE), aggrecanase, or a combination thereof.

Bristol-Myers Squibb Company

Hydantoin derivatives as inhibitors of tumor necrosis factor-alpha converting enzyme (TACE)

A highly safe therapeutic agent for intractable vasculitis such as malignant rheumatoid arthritis contains a hydantoin derivative represented by the formula (I) or a pharmaceutically acceptable salt thereof as an effective ingredient: ##STR1##wherein each of R.sub.1, and R.sub.2, which may be the same or different, represents hydrogen, an alkyl group or a cycloalkyl group; and each of X and Y, which may be the same or different, represents hydrogen, a hydroxyl group, an alkyl group or an alkoxy group, or X and Y together represent an oxo group. The hydantoin derivatives significantly suppress the generation of arthritis and arteritis (cutaneous ulcer and auricular infarcted necrosis) which are naturally developed in model animals (MRL/lpr), and further significantly elongate the survival rate of MRL/lpr mice. Consequently, the hydantoin derivatives, having low toxicity and little side effects are very useful as highly safe therapeutic agents for intractable vasculitis such as malignant rheumatoid arthritis.

hydantoin/necrosis

Hydantoin derivatives as inhibitors of tumor necrosis factor-alpha converting enzyme (TACE)

Therapeutic agent for intractable vasculitis

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