Matrix metalloproteinases (MMPs) are a group of enzymes that have been
implicated in the pathological destruction of connective tissue and
basement membranes. These zinc containing endopeptidases consist of
several subsets of enzymes including collagenases, stromelysins and
gelatinases. TNF converting enzyme (TACE), a pro-inflammatory cytokine,
catalyzes the formation of TNF-.alpha. from membrane bound TNF-.alpha.
precursor protein. It is expected that small molecule inhibitors of MMPs
and TACE therefore have the potential for treating a variety of disease
states. The present invention provides low molecular weight, non-peptide
inhibitors of matrix metalloproteinases (is) and TNF-.alpha. converting
enzyme (TACE) for the treatment of arthritis, tumor metastasis, tissue
ulceration, abnormal wound healing, periodontal disease, bone disease,
diabetes (insulin resistance) and HIV infection having the formula
##STR1##
wherein R.sup.2 and R.sup.3 form a heterocyclic ring and A is S, S(O), or
S(O)2, and R.sup.1 and R.sup.4 are defined herein.