British Biotech Pharmaceuticals Limited

British Bio-technology Limited

Jonathan P Dickens

Michael John Crimmin

Alan H Davidson

Colin Campion

Raymond Paul Beckett

Christopher D Floyd

Mark Whittaker

Christopher Norman Lewis

The present invention relates to intermediates, useful for the preparation of therapeutically active hydroxamic acid derivatives which are inhibitors of metalloproteinases involved in tissue degradation, and are inhibitors of the release of tumour necrosis factor from cells.

Dioxolane intermediates

Compounds of general Formula I: ##STR1## are presented which have collagenase inhibition activity and are useful in the management of disease involving tissue degradation and the promotion of wound healing. Representative diseases involving include arthropathy (particularly rheumatoid arthritis), inflammation, dermatological diseases, bone resorption disease and tumor invasion.

Compounds

Hydroxamic acid derivatives as metalloproteinase inhibitors

Natural amino acid derivatives as metalloproteinase inhibitors

Compounds of general formula I: ##STR1## wherein: R.sup.1 represents a C.sub.1 -C.sub.6 alkyl, phenyl, thiophenyl, substituted phenyl, phenyl(C.sub.1 -C.sub.6)alkyl, heterocyclyl, (C.sub.1 -C.sub.6)alkylcarbonyl phenacyl or substituted phenacyl group; or, when n=O, R.sup.1 represents SR.sup.x, wherein R.sup.x represents a group: ##STR2## R.sup.2 represents a hydrogen atom or a C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkenyl, phenyl(C.sub.1 -C.sub.6)alkyl, cycloalkyl(C.sub.1 -C.sub.6)alkyl or cycloalkenyl(C.sub.1 -C.sub.6)alkyl group;

Hydroxamic acid based collagenase inhibitors

Compounds of general formula I: ##STR1## wherein: A represents the group --NH.sub.2, a substituted acyclic amine or a heterocyclic base; have collagenase inhibition activity and are useful in the management of disease involving tissue degradation and/or the promotion of wound healing. Diseases involving tissue degradation include arthropathy (particularly rheumatoid arthritis), inflammation, dermatological diseases, bone resorption diseases and tumour invasion.

Compounds of general formula I: ##STR1## wherein: each of R.sup.1 -R.sup.8, k, and V represent disclosed functional groups that have been chosen such that all disclosed variations of compound I and their pharmaceutically and veterinarily acceptable acid addition salts and hydrates are antagonists of platelet activating factor (PAF) and as such are useful in the treatment or amelioration of various diseases or disorders mediated by PAF.

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Buckinghamshire, United Kingdom

Jonathan P Dickens