| abstract |
It is related to novel derivatives of the ortho-sulfonamido arylhydroxamic acids inhibitors of TACE and MMP are represented by the formula I in which the portion of hydroxamic acid and the portion of sulfonamido are linked to the adjacent compounds of group A where: A is phenyl or naphthyl , optionally substituted by R1, R2, R3 and R4; Z is aryl, heteroaryl, or heteroaryl fused to phenyl, where aryl is phenyl or naphthyl optionally substituted by R1, R2, R3, and R4, heteroaryl is a 5-6 membered heteroaromatic ring with 1 to 3 heteroatoms independently selected from O, S, or N , and optionally substituted by R1, R2, R3 and R4; and when heteroaryl is fused to phenyl, one or both rings may be optionally substituted by R1, R2, R3 and R4; and R1, R2, R3, R4, R5, R6, R7, R8 and R9 are described in the specification, and the pharmaceutically acceptable salts thereof and the optical and diastereomeric isomers thereof, which are useful for the treatment of diseases in which these enzymes are involved, such as arthritis, metastasis and tumor development, angiogenesis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, proteinuria, aortic aneurysm disease, degenerative loss of cartilage after traumatic joint injury, demyelinating diseases of the nervous system, graft rejection, cachexia, norexia, inflammation, fever, insulin resistance, septic shock, congestive heart failure, inflammatory disease of the central nervous system, inflammatory bowel disease, HIV infection, age-related macular degeneration, diabetic retinopathy, vitreoretinopathy proliferates tiva, retinopathy of prematurity |