Alpha-hydroxy,-amino and -fluoro derivatives of beta-sulphonyl hydroxamic acids as matrix metalloproteinases inhibitors

A compound of formula I

• 10
• or pharmaceutical acceptable salts thereof wherein:
• R1 is
• a) C4-12 alkyl,
• b) C4-12 alkenyl,
• c) C4-12 alkynyl,
• d) —(CH2)h—C3-8 cycloalkyl,
• e) —(CH2)h-aryl,
• f) —(CH2)h-het,
• R2 is
• a) C1-12 alkyl,
• b) C2-12 alkenyl,
• c) C2-12 alkynyl,
• d) —(CH2)h—C3-8 cycloalkyl,
• e) —(CH2)h—C3-8 cycloalkenyl,
• f) —(CH2)h-aryl
• g) —(CH2)h-het,
• h) —(CH2)h-Q,
• i) —(CH2)i-Q or —(CH2)l—X—R4, optionally the —(CH2)l— chain can be substituted with one or two C1-4 alkyl or phenyl, which in turn can be substituted with one to three halo or C1-4 alkyl, or
• l) —(CH2)hCHR5R6;
• R3 is
• a) H,
• b) C3-6 cycloalkyl,
• c) C1-4 alkyl, or
• d) —(CH2)h-phenyl;
• X is
• a) —O—,
• b) —S(═O)j-,
• c) —NR7—,
• d) —S(═O)2NR8—, or
• e) —C(═O)—;
• R4 is
• a) H,
• b) C1-8 alkyl,
• c) —(CH2)h-phenyl, or
• d) —(CH2)h-het;
• R5 is
• a) C1-4 alkyl, or
• b) —C(═O)R3;
• R6 is
• a) —C(═O)R3, or
• b) —(CH2)hC(═O)R3;
• R7 is
• a) H,
• b) C1-4 alkyl,
• c) —(CH2)h-phenyl,
• d) —C(═O)—R3,
• e) —S(═O)2R3, or
• f) —C(═O)OR3;
• R8 is
• a) C1-4 alkyl, or
• b) —(CH2)h-phenyl;
• Y is
• a) —OH,
• b) —NR9R10, or
• c) fluoro;
• R9 and R10 are the same and different and are
• a) H,
• b) —C(═O)—R3,
• c) —C(═O)—OR3, or
• d) —C(═O)—NHR3;
• aryl is monocarbocyclic, or bicarbocyclic aromatic moiety;
• het is 5- to 10-membered unsaturated monomonocyclic or bicyclic heterocyclic moiety having one to three atoms selected from the group consisting of oxygen, nitrogen, and sulfur;
• Q is 5- to 10-membered saturated monocyclic or bicyclic heterocyclic moiety having one to two atoms selected from the group consisting of oxygen, nitrogen, and sulfur;
• aryl, het, C1-12 alkyl, C1-4 alkyl C2-12 alkenyl, C2-12 alkynyl, —C3-8 cycloalkyl, —C3-8 cycloalkenyl, Q and phenyl being optionally substituted;
• h is 0, 1, 2, 3, 4, 5, or 6;
• i is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;
• j is 0, 1, or 2;
• and with the following provisos:
• a) where R2 is C1-6 alkyl, Y is other than —NR9R10,
• b) where h is 0, het is attached to the α-position via carbon atom of heterocyclic moiety, and
• c) where h is 0, Q is attached to the α-position via carbon atom of heterocyclic moiety.