Compound, use of it, pharmaceutical composition, and processes to inhibit intracellular release of tumor necrosis factor alpha, to inhibit a matrix metalloprotease, to inhibit the flow of potent ectodomains from the cell surface, to inhibit the growth of tumor metastases , or a process for the treatment of diabetes, or a process for the treatment of arthritis, in a mammalian subject.

摘要

"COMPOUND, USE OF THE SAME, PHARMACEUTICAL COMPOSITION, AND, PROCESSES TO INHIBIT THE INTRACELLULAR RELEASE OF THE ALPHA TACTORAL NECROSIS FACTOR, TO INHIBIT A MATRIX METALOPROTEASE, INHIBITION OF THE EXCHANGE OF ECTODOMINISTS OF THE PHOTOGRAPHY OF HYPOTHESIS OF PHOTOMINE. TUMOR, OR A PROCESS FOR THE TREATMENT OF DIABETES, OR A PROCESS FOR THE TREATMENT OF ARTHRITIS, IN A MAMMALIAN SUBJECT ". A family of compounds having the general structural formula (I) where W is a reserve hydroxamic acid group (a); R ~ 5 ~ is hydrogen or lower alkyl; R ~ 6 ~ is (b); where Z ~ 1 ~ is heteroarylene; preferably: R ~ 1 ~ is methyl, ethyl, isopropyl, n-propyl or 3,3,3-trifluoro-n-propyl; R ~ 2 ~ is isobutyl or sec-butyl; R ~ 3 ~ is hydrogen; R ~ 4 ~ is tert-butyl, sec-butyl, 1-methoxy-1-ethyl or 2- (2-pyridylcarbonylamino) -1-ethyl; R ~ 5 ~ is hydrogen; and R ~ 6 ~ is 2-thiazolyl or 2-pyridyl. Such compounds have a potent inhibition of MMP's, free cell TNF convertase enzyme and TNF release from cells, and in some cases inhibit TNF convertase and TNF release from cells preferably the matrix metalloproteases.