| 摘要 |
The compounds of formula I are inhibitors of matrix metalloproteinases, particularly stromelysin-1 and gelatinase A (72 kD gelatinase). The compounds may be used in medicaments to treat multiple sclerosis, atherosclerotic plaque rupture, aortic aneurism, heart failure, restenosis, periodontal disease, corneal ulceration, burns, decubital ulcers, chronic ulcers or wounds, cancer metastasis, tumour angiogenesis, arthritis, or other autoimmune or inflammatory disorders dependent upon tissue invasion by leukocytes. In formula I: Ar is selected from phenyl or phenyl substituted with alkyl, NO2, halogen, OR5, CN, CO2R5, SO3R5, CHO, COR5, CONHR5, NHR5 or NHCOR5; R1 is hydrogen, methyl, NO2, Cl, NH2, NHCO2CH3, OH or CO2H; R2, R3 and Ra are the same or different and are independently selected from hydrogen, alkyl, (CH2)v-phenyl, (CH2)v-indolyl, (CH2)v-cycloalkyl, (CH2)tNR6R6a, (CH2)vR7, (CH2)vCO2R5, (CH2)vCONR6R6a or (CH2)vSR5; m is zero or 1; Y is CH; z is zero or 1; W is CHR8; n is zero or 1; R4 is OH, NR6R6a or NHOR9; R5 is hydrogen or alkyl; v is 1 to 5; X is O or S; p and q are independently 1 to 5, provided that p+q is not greater than 5; t is 1 to 9; R6 and R6a are each the same or different and are hydrogen or alkyl; R7 is 1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl, or 1,3-dihydro-1,3-dioxo-benzo[f]isoindol-2-yl; R8 is hydrogen or alkyl; and R9 is hydrogen, alkyl, or benzyl.
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