YU24795A - HYDROXAMIC ACID DERIVATIVES WITH TRICYCLIC SUBSTITUTION - Google Patents

Abstract

The invention provides hydroxamic acid derivatives of the general formula wherein R represents cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; R2 is a saturated monocyclic or bridged 5 to 8 membered N-heterocyclic ring which is attached via an N atom and which, when monocyclic, optionally contains NR4, O, S, SO or SO2 as a ring member and is optionally substituted on one or more C atoms with 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 a (lower alkyl) carbamoyl, di (lower alkyl) carbamoyl or hydroxyimino group; R3 is a 5 or 6 membered heterocyclic ring, which is (a) bonded via the N atoms, (b) optionally contains N, O and / or, S, SO or SO2 as an additional ring member, (c) is replaced with oxo on one or both atoms adjacent to the bonding N atom and (d) optionally bonded with a benz bond or optionally substituted on one or more C atoms with lower alkyl or oxo and / or on any additional N atoms or atoms, with the lower. an alkyl or aryl group; R4 is hydrogen, lower alkyl, aryl, aralkyl or a protecting group; mark 1 or 2 is 1-4, and pharmaceutically acceptable salts thereof, which are collagenase inhibitors and useful in the control or prevention of degenerative joint diseases, such as rheumatoid arthritis and osteoarthritis, or in the treatment of invasive tumors, atrosclerosis or ultraple sclerosis. They can be produced either by hydroxamidation of the corresponding new carboxylic acid or by deprotection of one suitable new benzyloxycarbamoyl compound.