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 compositions comprising a compound of the general formula:
##STR1##
wherein X is a Zn(II) chelating group and selected from the group
consisting of (CH.sub.2).sub.n OH, (CH.sub.2).sub.n NH.sub.2,
(CH.sub.2).sub.n SH, (CH.sub.2).sub.m COOH, (CH.sub.2).sub.m COOR,
(CH.sub.2).sub.m CONH.sub.2, (CH.sub.2).sub.m" CONH--OH, (CH.sub.2).sub.m"
CONH--R, and (CH2).sub.n' O(PO.sub.3).sub.m".sup.(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.sub.m', H.sub.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 TNF.alpha. to TNF.alpha.-RI.
A invenção divulga métodos de tratamento e de prevenção para disorders de TNF.alpha.-related e disorders MMP-relacionados e combina-os útil em tais tratamentos. No detalhe, as composições pharmaceutical dos dislcoses da invenção que compreendem um composto da fórmula geral: ## do ## STR1 wherein X é um grupo chelating de Zn(II) e selecionado de consistir do grupo (CH.sub.2).sub.n OH, (CH.sub.2).sub.n NH.sub.2, (CH.sub.2).sub.n SH, (CH.sub.2).sub.m COOH, (CH.sub.2).sub.m COOR, (CH.sub.2).sub.m CONH.sub.2, (CH.sub.2).sub.m "CONH -- oh, (CH.sub.2).sub.m" CONH -- r, e (CH2).sub.n ' O(PO.sub.3).sub.m".sup.(m"+1), wherein n=2, 3, 4, ou 5, n'=2 ou 3, m=1, 2, 3, ou 4, m'=1, 2, 3, 4, 5, ou 6, m"=1, 2, 3, e R= -- C.sub.m ', H.sub.2m'+1 ou grupos aryl, especial 1-[3,4-dihydroxy-5-(2-hydroxyethyl)-tetrahydrofuran-2-yl]pyrimidine-2,4(1H, 3H)-dione, que tem inhibitory um efeito e no emperramento de TNF.alpha. a TNF.alpha.-RI.
