| abstract |
A hydroxamic acid derivative or a pharmaceutical acceptable salt thereof has the formula I HO-N(H)-C(=O)-C(R2)(Y)-CH2-S(O)2-R1 wherein: R1 is alkyl, alkenyl, alkynyl, -(CH2)h-cycloalkyl, -(CH2)h-aryl or -(CH2)h-het; R2 is alkyl, alkenyl, alkynyl, -(CH2)h-cycloalkyl, -(CH2)h-cycloalkenyl, -(CH2)h-aryl, -(CH2)h-het, -(CH2)h-CHR5R6, -(CH2)h-Q, -(CH2)i-Q or -(CH2)i-X-R4; the -(CH2)i- chain can optionally be substituted with one or two alkyl or phenyl; R3 is H, cycloalkyl, alkyl or -(CH2)h-phenyl; X is -O-, -S(=O)j-, -NR7-, -S(=O)2NR8- or -C(=O)-; R4 is H, alkyl, -(CH2)h-phenyl or -(CH2)h-het; R5 is alkyl or -C(=O)R3; R6 is -C(=O)R3 or -(CH2)h-C(=O)R3; R7 is H, alkyl, -(CH2)h-phenyl, -C(=O)-R3, -S(=O)2R3 or -C(=O)OR3; R8 is alkyl or -(CH2)h-phenyl; Y is -OH, -NR9R10 or fluoro; R9 and R10 are independently H, -C(=O)-R3, -C(=O)-OR3 or -C(=O)-NHR3; aryl is mono- or bi-carbocyclic aromatic moiety; het is 5-to 10-membered unsaturated mono- or bi- heterocyclic moiety having one to three atoms selected from oxygen, nitrogen and sulphur; Q is 5-to 10-membered saturated mono- or bi- heterocyclic moiety having one to two atoms selected from oxygen, nitrogen, and sulphur; aryl, het, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, Q and phenyl being optionally substituted; h is 0 to 6; i is 5 to 10; j is 0 to 2 provided : a) when R2 is alkyl, Y is other than -NR9R10, b) when h is 0, het is attached to the a-position via carbon atom of heterocyclic moiety or c) where h is 0, Q is attached to the a-position via carbon atom of heterocyclic moiety. A pharmaceutical composition thereof is useful to inhibit excess matrix metalloproteinase. |