Hydroxamic and carboxylic acid derivatives having MMP and TNF inhibitory activity

A method for the treatment of a condition associated with matrix metalloproteinases or that is mediated by TNF α or enzymes involved in the shedding of L-selectin, CD23, the TNF receptors, IL-6 receptors, or IL-1 receptors, wherein said method comprises administration of an effective amount of a composition comprising a compound represented by formula (I):

• wherein
• m is 0-2;
• X is S(O)1-2;
• Y is OH or NHOH;
• R1 is H or a group (substituted or unsubstituted with R7) selected from the group consisting of C1-6 alkyl, C2-6 alkenyl, aryl, C1-6 alkyl-aryl, heteroaryl, C1-6 alkyl-heteroaryl, heterocycloalkyl, C1-6 alkyl-heterocycloalkyl, cycloalkyl, and C1-6 alkyl-cycloalkyl, and R2 is H or C1-6 alkyl;
• or CR1R2 is a cycloalkyl or heterocycloalkyl ring substituted or unsubstituted with R7 or a group (substituted or unsubstituted with R7) selected from the group consisting of C1-6 alkyl, aryl, C1-6 alkyl-aryl, heteroaryl, and C1-6 alkyl-heteroaryl;
• each B is the same or different and is selected from the group consisting of H, C1-6 alkyl-aryl, C1-6 alkyl, cycloalkyl, C1-6 alkyl-cycloalkyl, cycloalkenyl, heterocycloalkenyl, C1-6 alkylheteroaryl, heterocycloalkyl, C1-6 alkyl-heterocycloalkyl, aryl, and heteroaryl, any of which groups is substituted or unsubstituted by a substituent selected from the group consisting of R3, C1-6 alkyl-R3, C2-6 alkenyl-R3, aryl (substituted or unsubstituted with R3), aryl-C1-6 alkyl-R3, C1-6 alkyl-aryl (substituted or unsubstituted with R3), C1-6 alkyl-heteroaryl(substituted or unsubstituted with R3), aryl-C2-6, alkenyl-R5, heteroaryl (substituted or unsubstituted with R3), heteroaryl-C1-6 alkyl-R3, cycloalkyl (substituted or unsubstituted with R3), and heterocycloalkyl (substituted or unsubstituted with R3), provided that NB2 is not NH2,
• or B—N—B is a heterocycloalkyl ring substituted with ═O or ═NOR4,
• or, when neither R1 nor R2 is H, B—N—B is a heterocycloalkyl or heterocyclalkenyl ring substituted or unsubstituted by a substituent selected from the group consisting of R3, C1-6 alkyl-R3, C2-6 alkenyl-R3, aryl (substituted or unsubstituted with R3), aryl-C1-6 alkyl-R3, C1-6 alkyl-aryl (substituted or unsubstituted with R3), C1-6 alkyl-heteroaryl (substituted or unsubstituted with R3), aryl-C2-6 alkenyl-R5, heteroaryl (substituted or unsubstituted with R3), heteroaryl-C1-6 alkyl-R3, cycloalkyl (substituted or unsubstituted with R3), and heterocycloalkyl (substituted or unsubstituted with R3);
• R3 is selected from the group consisting of C1-6 alkyl, C2-6 alkenyl-R5, halogen, CN, NO2, N(R4)2, OR4, C(═NOR6)R4, CON(R4)2, COR4, CO2R8, NR4R5, S(O)0-2R6, and SO2N(R4)2;
• R4 is selected from the group consisting of H, C1-6 alkyl, aryl, C1-6 alkyl-aryl, heteroaryl, C1-6 alkyl-heteroaryl, cycloalkyl, C1-6 alkyl-cycloalkyl, heterocycloalkyl, and C1-6 alkyl-heterocycloalkyl, wherein said group is substituted or unsubstituted with a substituent selected from the group consisting of R6, COR6, SO0-2R6, CO2R6, OR6, CONR8R6, NR8R6, halogen, CN, SO2NR8R6, and NO2, and for each case of N(R4)2 the R4 groups are the same or different or N(R4)2 is heterocycloalkyl substituted or unsubstituted with a substituent selected from the group consisting of R6, COR6, SO0-2 R6CO2R6, OR6, CONR8R6, NR8R6, halogen, CN, SO2NR8R6, and NO2;
• R5 is selected from the group consisting of COR4, CON(R4)2, CO2R6, and SO2R6;
• R6 is selected from the group consisting of C1-6 alkyl, aryl, C1-6 alkyl-aryl, heteroaryl, and C1-6 alkyl-heteroaryl;
• R7 is selected from the group consisting of OR4, COR4, CO2R8, CON(R4)2, NR4R5, S(O)0-2 R6, SO2N(R4)2, halogen, CN, and cycloimidyl (substituted or unsubstituted with R8);
• and
• R8 is H or C1-6 alkyl;
• and the salts, solvates, hydrates, N-oxides, protected amino, protected carboxy, or protected hydroxamic acid derivatives thereof.