| abstract |
The invention provides hydroxamic acid derivatives of the formulan nwherein R 1 represents 1-7C alkyl; R 2 represents hydrogen, 1-6C alkyl or a group of the formula -(CH 2 ) n -aryl or -(CH 2 ) n -Het in which n stands for 1-4 and Het represents a 5- or 6-membered N-heterocyclic ring which (a) is attached via the N atom, (b) optionally contains N, O and/or S as additional hetero atom(s) in a position or positions other than adjacent to the linking N atom, (c) is substituted by oxo on one or both C atoms adjacent to the linking N atom and (d) is optionally benz-fused or optionally substituted on one or more other carbon atoms by 1-6C alkyl or oxo and/or on any additional N atom(s) by 1-6C alkyl; R 3 represents the characterizing group of a natural or non-natural a-amino acid in which any functional group present may be protected, with the proviso that R 3 does not represent hydrogen; R 4 represents carboxyl, (1-6C alkoxy)-carbonyl, carbamoyl or (1-6C alkyl)-carbamoyl; R 5 represents the characterizing group of a naturally occurring a-amino acid in which any functional group present may be protected; and R 6 represents hydrogen; or R 4 , R 5 and R 6 each individually represent hydrogen or 1-6C alkyl, and their pharmaceutically acceptable salts, which are matrix metalloproteinase inhibitors useful for the control or prevention of degenerative joint diseases such as rheumatoid arthritis and osteoarthritis or for the treatment of invasive tumours, atherosclerosis or multiple sclerosis. They can be manufactured according to generally known methods by deprotecting a corresponding novel benzyloxyamino compound or hydroxamidating a corresponding novel amino acid or activated derivative thereof. |