| abstract |
The compounds of the formula (1) are useful for the treatment of pathological disorders in which TNF-alpha mediates, such as rheumatoid arthritis, osteoarthritis, sepsis, AIDS, ulcerative colitis, multiple sclerosis, Crohn's disease and degenerative cartilage loss. Hydroxamic acids having the formula (1) in which the C (= O) NHOH portion and the -NR5- portion are attached to adjacent carbons of group A; where A is 5-6 membered heteroaryl, with 1 to 3 heteroatoms selected from N, NR9, S and O; X is SO2 or -P (O) R10; Y is 5-10 membered mono or bicyclic aryl or heteroaryl with 1 to 3 heteroatoms selected from N, NRg, S and O; with the proviso that X and Z cannot be attached to adjacent atoms of Y; Z is O, NH, CH2 or S; R5 is hydrogen or alkyl of 1-6 carbon atoms; each of R6 and R7 is, independently, hydrogen, alkyl of 1-6 carbon atoms; -CN, -CCH; and R8 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 3-6 carbon atoms, aryl, heteroaryl of 5 to 10 members with 1 to 3 heteroatoms selected from N, NRg S and O or 5-9 membered heterocycloalkyl with 1 or 2 heteroatoms selected from N, NRg, S and O; Rg is hydrogen, aryl, alkyl of 1-6 atoms or cycloalkyl of 3-6 carbon atoms; and R10 is alkyl of 1-6 carbon atoms, cycloalkyl of 3-6 carbon atoms, aryl or heteroaryl or a pharmaceutically acceptable salt thereof. |