Uridine derivatives as Matrix Metalloproteinase (MMP) and Tumor Necrosis Factor (TNF) inhibitors for the treatment of cancer

摘要

The invention discloses methods of treatment and prevention for TNFα-related disorders and MMP-related disorders and compounds useful in such treatments. In particular, the invention dislcoses pharmaceutical compositions comprising a compound of the general formula:    wherein X is a Zn(II) chelating group and selected from the group consisting of (CH₂)_nOH, (CH₂)_nNH₂, (CH₂)_nSH, (CH₂)_mCOOH, (CH₂)_mCOOR, (CH₂)_mCONH₂, (CH₂)_m''CONH-OH, (CH₂)_m''CONH-R, and (CH₂)_n'O(PO₃)_m''^(m''+1), 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'H_2m'+1 or aryl groups, especially 1-[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 TNFα to TNFα-R1.