Hydroxamic acid derivatives

A pharmaceutical composition for use in therapy, comprising a compound of formula (I)

• 5
• wherein R2 is H, alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclo, heterocycloalkyl or cycloalkyl (any of which may be optionally substituted with one or more substituents selected from R4, W and WR4);
• and
• R3 is H or alkyl;
• or R2, R3 and the carbon atom to which they are attached together represent a carbocyclic or heterocyclic ring (either of which may be substituted with one or more substitients chosen from R4, W and WR4);
• A is a heterocyclic ring (attached to SO2 through a nitrogen atom) optionally substituted with R4;
• B is an aryl or heteroaryl ring, optionally substituted with one or more R5;
• D is an aryl or heteroaryl ring, optionally substituted with one or more R5, or a heterocyclic ring (attached through a carbon atom) optionally substituted with R4 at any available carbon atom or with R14 at any available nitrogen atom;
• provided that B and D are not both phenyl;
• R4 is OR6, COR10, CO2R9, CONR7R8, NR10R11, S(O)qR10, S(O)qNR7R8, CN, ═O or ═NOR10, provided that R4 is not ═O or NOR10 if a substituent on an aromatic ring;
• R5 is alkyl, cycloalkyl, CF3, OR6, COR10, S(O)qR10, CO2R9, CONR7R8, S(O)qNR7R8, halogen, NR10R11 or CN;
• R6 is H, alkyl, CF3, CHF2, CH2F, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl or cycloalkylalkyl;
• R7 and R8, which may be the same or different, are each H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl, cycloalkylalkyl, or R7 and R8 and the nitrogen to which they are attached together represent a heterocyclic ring;
• R9 is H, alkyl or cycloalkyl;
• R10 is H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl or cycloalkylalkyl;
• and
• R11 is H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl, cycloalkylalkyl, COR12, CONR7R8, S(O)qR12 or S(O)qNR7R8;
• or R10 and R11 and the nitrogen atom to which they are attached together represent a heterocyclic ring optionally substituted by R13;
• R12 or OR6 or R13;
• R13 is alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl or cycloalkylalkyl;
• R14 is H, alkyl or cycloalkyl
• q is 0, 1 or 2;
• W is alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclo or heterocycloalkyl;
• and
• X is —O—, —CO—, S(O)q—, —N(R10)—, or is absent;
• or a salt, solvate, hydrate, N-oxide, protected amino, protected carboxy or protected hydroxamic acid derivative thereof;
• and a pharmaceutically-acceptable diluent or carrier.

A method for the treatment of cancer;

• inflammation;
• or an autoimmune, infectious or ocular disease;
• wherein said method comprises administering to a patient in need of such treatment a compound of formula (I)
• 6
• wherein R2 is H, alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclo, heterocycloalkyl or cycloalkyl (any of which may be optionally substituted with one or more substituents selected from R4, W and WR4);
• and
• R3 is H or alkyl;
• or R2, R3 and the carbon atom to which they are attached together represent a carbocyclic or heterocyclic ring (either of which may be substituted with one or more substitients chosen from R4, W and WR4);
• A is a heterocyclic ring (attached to SO2 through a nitrogen atom) optionally substituted with R4;
• B is an aryl or heteroaryl ring, optionally substituted with one or more R5;
• D is an aryl or heteroaryl ring, optionally substituted with one or more R5, or a heterocyclic ring (attached through a carbon atom) optionally substituted with R4 at any available carbon atom or with R14 at any available nitrogen atom;
• provided that B and D are not both phenyl;
• R4 is OR6, COR10, CO2R9, CONR7R8, NR10R11, S(O)qR10, S(O)qNR7R8, CN, ═O or ═NOR10, provided that R4 is not ═O or NOR10 if a substituent on an aromatic ring;
• R5 is alkyl, cycloalkyl, CF3, OR6, COR10, S(O)qR10, O CO2R9, CONR7R8, S(O)qNR7R8, halogen, NR10R11 or CN;
• R6 is H, alkyl, CF3, CHF2, CH2F, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl or cycloalkylalkyl;
• R7 and R8, which may be the same or different, are each H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl, cycloalkylalkyl, or R7 and R8 and the nitrogen to which they are attached together represent a heterocyclic ring;
• R9 is H, alkyl or cycloalkyl;
• R10 is H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl or cycloalkylalkyl;
• and
• R11 is H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl, cycloalkylalkyl, COR12, CONR7R8, S(O)qR12 or S(O)qNR7R8;
• or R10 and R11 and the nitrogen atom to which they are attached together represent a heterocyclic ring optionally substituted by R13;
• R12 or OR6 or R13;
• R13 is alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl or cycloalkylalkyl;
• R14 is H, alkyl or cycloalkyl
• q is O, 1 or 2;
• W is alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclo or heterocycloalkyl;
• and
• X is —O—, —CO—, S(O)q—, —N(R10)—, or is absent;
• or a salt, solvate, hydrate, N-oxide, protected amino, protected carboxy or protected hydroxamic acid derivative thereof.

A method for the treatment of graft versus host reactions, psoriasis, atopic dermatitis, rhinitis, eczema, systemic lupus erythematosus, solid organ transplant or cystic fibrosis, wherein said method comprises administering to a patient in need of such treatment a compound of formula (I)

• 7
• wherein R2 is H, alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclo, heterocycloalkyl or cycloalkyl (any of which may be optionally substituted with one or more substituents selected from R4, W and WR4);
• and
• R3 is H or alkyl;
• or R2, R3 and the carbon atom to which they are attached together represent a carbocyclic or heterocyclic ring (either of which may be substituted with one or more substitients chosen from R4, W and WR4);
• A is a heterocyclic ring (attached to SO2 through a nitrogen atom) optionally substituted with R4;
• B is an aryl or heteroaryl ring, optionally substituted with one or more R5;
• D is an aryl or heteroaryl ring, optionally substituted with one or more R5, or a heterocyclic ring (attached through a carbon atom) optionally substituted with R4 at any available carbon atom or with R14 at any available nitrogen atom;
• provided that B and D are not both phenyl;
• R4 is OR6, COR10, CO2R9, CONR7R8, NR10 R11, S(O)qR10, S(O)qNR7R8, CN, ═O or ═NOR10, provided that R4 is not ═O or NOR10 if a substituent on an aromatic ring;
• R5 is alkyl, cycloalkyl, CF3, OR6, COR10, S(O)Rq10, COR92, CONR7R8, S(O)qNR7R8, halogen, NR10OR11 or CN;
• R6 is H, alkyl, CF3, CHF2, CH2F, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl or cycloalkylalkyl;
• R7 and R8, which may be the same or different, are each H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl, cycloalkylalkyl, or R7 and R8 and the nitrogen to which they are attached together represent a heterocyclic ring;
• R9 is H, alkyl or cycloalkyl;
• R10 is H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl or cycloalkylalkyl;
• and
• R11 is H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl, cycloalkylalkyl, COR12, CONR7R8, S(O)qR12 or S(O)qNR7R8;
• or R10 and R11 and the nitrogen atom to which they are attached together represent a heterocyclic ring optionally substituted by R13;
• R12 or OR6 or R13;
• R13 is alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl or cycloalkylalkyl;
• R14 is H, alkyl or cycloalkyl
• q is 0, 1 or 2;
• W is alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclo or heterocycloalkyl;
• and
• X is —O—, —CO—, S(O)q—, —N(R10)—, or is absent;
• or a salt, solvate, hydrate, N-oxide, protected amino, protected carboxy or protected hydroxamic acid derivative thereof.

A method for the treatment of rheumatoid arthritis, osteoarthritis, osteoporosis, Crohn's Disease, ulcerative colitis, multiple sclerosis, periodonitis, bone resorption, bacterial infections, epidermolysis bullosa, tumour growth, angiogenesis, ophthalmological disease, retinopathy, asthma, emphysema, bronchitis or chronic obstructive pulmonary disease (COPD);

• wherein said method comprises administering to a patient in need of such treatment a compound of formula (I)
• 8
• wherein R2 is H, alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclo, heterocycloalkyl or cycloalkyl (any of which may be optionally substituted with one or more substituents selected from R4, W and WR4);
• and
• R3 is H or alkyl;
• or R2, R3 and the carbon atom to which they are attached together represent a carbocyclic or heterocyclic ring (either of which may be substituted with one or more substitients chosen from R4, W and WR4);
• A is a heterocyclic ring (attached to SO2 through a nitrogen atom) optionally substituted with R4;
• B is an aryl or heteroaryl ring, optionally substituted with one or more R5;
• D is an aryl or heteroaryl ring, optionally substituted with one or more R5, or a heterocyclic ring (attached through a carbon atom) optionally substituted with R4 at any available carbon atom or with R14 at any available nitrogen atom;
• provided that B and D are not both phenyl;
• R4 is OR6, COR10, CO2R9, CONR7R8, NR10 R11, S(O)qR10, S(O)qNR7R8, CN, ═O or NOR10, provided that R4 is not ═O or NOR10 if a substituent on an aromatic ring;
• R5 is alkyl, cycloalkyl, CF3, OR6, COR10, S(O)Rq10, CO R92, CONR7R8, S(O)qNR7R8, halogen, NR10R11 or CN;
• R6 is H, alkyl, CF3, CHF2, CH F2, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl or cycloalkylalkyl;
• R7 and R8, which may be the same or different, are each H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl, cycloalkylalkyl, or R7 and R8 and the nitrogen to which they are attached together represent a heterocyclic ring;
• R9 is H, alkyl or cycloalkyl;
• R10 is H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl or cycloalkylalkyl;
• and
• R11 is H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl, cycloalkylalkyl, COR12, CONR7R8, S(O)qR12 or S(O)qNR7R8;
• or R10 and R11 and the nitrogen atom to which they are attached together represent a heterocyclic ring optionally substituted by R13;
• R12 or OR6 or R13;
• R13 is alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl or cycloalkylalkyl;
• R14 is H, alkyl or cycloalkyl
• q is O, 1 or 2;
• W is alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclo or heterocycloalkyl;
• and
• X is —O—, —CO—, S(O)q—, —N(R10)—, or is absent;
• or a salt, solvate, hydrate, N-oxide, protected amino, protected carboxy or protected hydroxamic acid derivative thereof.