Hydroxamic acid derivatives useful for inhibiting gelatinase

摘要

The present invention relates to (i) hydroxamic acid derivatives of the formula (I): <CHEM> wherein R<1> is hydrogen, or C1-4 alkyl; R<2> is hydrogen, C1-8 alkyl, phenyl, C1-4 alkyl substituted by phenyl; E is -CONR<3>-, in which R<3> is hydrogen, C1-4 alkyl, etc., -NR<3>CO-, -CO-O-, -O-CO- etc.; A is hydrogen, C1-8 alkyl, C3-7 cycloalkyl, or Ar; J is bond, C2-4 alkylene etc.; G is -(CH2)m-, in which m is 2, 3 or 4, or <CHEM> in which R<6> and R<7> is hydrogen, C1-8 alkyl etc.; and non-toxic salts thereof, ii) processes for the preparation thereof, and iii) pharmaceutical agents containing them. The compounds of formula (I) are useful for prevention and/or treatment of diseases induced by overexpression or excess activity of gelatinases, for example, rheumatoid diseases, arthrosteitis, unusual bone resorption, osteoporosis, periodontitis, interstitial nephritis, arteriosclerosis, pulmonary emphysema, cirrhosis, cornea injury, metastasis of, invasion of or growth of tumor cells, autoimmune diseases (Crohn's disease, Sjogren's syndrome etc.), diseases caused by vascular emigration or infiltration of leukocytes, or arterialization in animals including human beings, especially human beings.