MATRIX METALLOPROTEINASE AND TUMOR NECROSIS FACTOR INHIBITORS

摘要

The invention discloses methods of treatment and prevention for TNF.alpha .- related disorders and MMP-related disorders and compounds useful in such treatments. In particular, the invention dislcoses pharmaceutical compositio ns comprising a compound of the general formula. (see fig I) wherein X is a Zn(II) chelating group and selected from the group consisting of (CH2)n OH, (CH2)n NH2, (CH2)n SH, (CH2)m COOH, (CH2)m COOR, (CH2)m CONH2, (CH2)m''CONH-OH, (CH2)m''CONH-R, and (CH2)n~O(PO3)m''(m''+ l), wherein n=2, 3, 4, or 5, n'=2 or 3, m=1, 2, 3, or 4, m'=1, 2, 3, 4, 5, or 6, m"=1, 2, 3, and R = - C m-H2m'+ l or aryl groups, especially ~-[3,4-dihydroxy-5-(2-hydroxyethyl )- tetrahydrofuran-2-yl]pyrimidine-2,4(1H,3H)-dione, which has an inhibitory effect on matrix metalloproteinase-2 (gelatinase A) and on the binding of TNF.alpha. t o TNF.alpha.-RI.