Hydroxamic acid derivatives with tricyclic substitution

摘要

The invention provides hydroxamic acid derivatives of the general formula wherein R<1> represents cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; R<2> represents a saturated 5- to 8-membered monocyclic or bridged N-heterocyclic ring which is attached via the N atom and which, when it is monocyclic, optionally contains NR<4>, O, S, SO or SO2 as a ring member and/or is optionally substituted on one or more C atoms by hydroxy, lower alkyl, lower alkoxy, oxo, ketalized oxo, amino, mono(lower alkyl)amino, di(lower alkyl)amino,carboxy, lower alkoxycarbonyl, hydroxy-methyl, lower alkoxymethyl, carbamoyl, mono(lower alkyl)-carbamoyl, di(lower alkyl)carbamoyl or hydroxyimino; R<3> 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, SO or SO2 as an additional ring member, (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 C atoms by lower alkyl or oxo and/or on any additional N atom(s) by lower alkyl or aryl; R<4> represents hydrogen, lower alkyl, aryl, aralkyl or a protecting group; m stands for 1 or 2 and n stands for 1-4, and pharmaceutically acceptable salts thereof, which are collagenase inhibitors useful in the control or prevention of degenerative joint diseases such as rheumatoid arthritis and osteoarthritis or in the treatment of invasive tumours, atherosclerosis or multiple sclerosis. They can be manufactured either by hydroxamidating a corresponding novel carboxylic acid or by deprotecting a corresponding novel benzyloxycarbamoyl compound.