Celltech Therapeutics Limited

Celltech Limited

Nigel Robert Beeley

Thomas A Millican

John Robert Porter

John R Morphy

David Parker

##STR1## Compounds of formula (1) are described wherein Y represents a halogen atom or a group --OR.sup.1 where R.sup.1 represents an optionally substituted alkyl group; R.sup.2 represents an optionally substituted cycloalkyl, cycloalkenyl or polycycloalkyl group; R.sup.3 represents a hydrogen atom or an alkyl, aryl or aralkyl group; R.sup.4 represents an aryl or heteroaryl group; X represents --O--, --S--, --CH.sub.2 -- or --N(R.sup.5)--, where R.sup.5 is a hydrogen atom or an alkyl group; n is zero or an integer or value 1, 2 or 3; and the salts, solvates and hydrates thereof. The compounds are selective phosphodiesterase IV inhibitors and are useful for the prophylaxis or treatment of inflammatory diseases.

Phenylaminocarbonyl derivatives and processes for their preparation

Methods of use for compounds of formula (I) are described wherein R represent a --CONHOH, carboxyl (--CO.sub.2 H) or esterified carboxyl group; R.sup.1 represents a hydrogen atom or an optionally substituted alkyl, alkenyl, aryl, aralkyl, heteroaralkyl or heteroarylthioalkyl group; R.sup.2 represents an optionally substituted phenylethyl, phenylpropyl or phenylbutyl group; R.sup.3 represents a hydrogen atom or an alkyl group; R.sup.4 represents a hydrogen atom or an alkyl group; R.sup.5 represents an optionally substituted alkyl or alkenyl group optionally interrupted by one or more --O-- or --S-- atoms or --N(R.sup.7)-- groups (where R.sup.7 is a hydrogen atom or a C.sub.1-6 alkyl group); X represents an amino (--NH.sub.2), or substituted amino, hydroxyl or substituted hydroxyl group; and the salts, solvates and hydrates thereof. The compounds are metalloproteinase inhibitors and in particular have a selective gelatinase action, and may be of use in the treatment of cancer to control the development of tumour metastases. ##STR1##

Peptidyl derivatives

Succinamide derivatives, processes for their preparation and their use

##STR1## Conjugate compounds are described comprising a compound of formula (1), wherein A is a group --Alk.sup.3 -- or --Alk.sup.3 N(R.sup.4)Alk.sup.1 --, Alk.sup.2, Alk.sup.3 and Alk.sup.4 which may be the same or different is each a C.sub.1-4 alkylene chain optionally substituted by one or more C.sub.1-6 alkyl groups; and R.sup.1, R.sup.2, R.sup.3 and R.sup.4, which may be the same or different, is each a hydrogen atom or a group--AlkR.sup.5 where Alk is an optionally substituted straight or branched C.sub.1-6 alkyl group and R.sup.5 is a hydrogen atom or a --CO.sub.2 H, --CONR.sup.6 R.sup.7 (where R.sup.6 and R.sup.7, which may be the same or different is each a hydrogen atom or an alkyl group) or --P(X.sup.1)(X.sup.2 R.sup.8)L group where X.sup.1 and X.sup.2 is each an oxygen or sulphur atom. R.sup.8 is a hydrogen atom or an alkyl group and L is an aliphatic, aromatic, or heteroaromatic group or a linker group with the proviso that at least one of R.sup.1, R.sup.2, R.sup.3 and R.sup.4 is a group AlkP(X.sup.1)(X.sup.2 R.sup.8)L where L is a linker group; and a metal complexes and/or salts thereof, coupled to a protein, peptide or carbohydrate. The conjugates are useful for imaging and in the treatment of abnormal cell disorders, such as in the treatment of tumours.

Conjugate compounds containing aza-macro-cycles and processes for their

##STR1## Metal complex of tetra-aza macrocycles of formula (1) wherein Alk.sup.1, Alk.sup.2, Alk.sup.3 and Alk.sup.4, which may be the same or different, is each a C.sub.1-4 alkylene chain optionally substituted by one or more optionally substituted C.sub.1-6 alkyl groups; and R.sup.1, R.sup.2, R.sup.3 and R.sup.4 which may be the same or different is each a hydrogen atom or a group AlkR.sup.5 where Alk is an optionally substituted straight or branched C.sub.1-6 alkyl group and R.sup.5 is a hydrogen atom or a --CO.sub.2 H,--CONR.sup.6 R.sup.7 [where R.sup.6 and R.sup.7, which may be the same or different, is each a hydrogen atom or a C.sub.1-6 alkyl group] or --P(X.sup.1)(X.sup.2 R.sup.8)R.sup.9 group where X.sup.1 and X.sup.2, which may be the same or different is each an oxygen or sulphur atom, R.sup.8 is a hydrogen atom or an alkyl group and R.sup.9 is an aliphatic, aromatic or heteroaromatic group, with the proviso that at least two of R.sup.1, R.sup.2, R.sup.3 and R.sup.4 is a group -AlkP(X.sup.1)(X.sup.2 R.sup.8)R.sup.9 or one or R.sup.1, R.sup.2, R.sup.3 and R.sup.4 is a group -AlkP(X.sup.1)(X.sup.2 R.sup.8)R.sup.9 and at least one of the remaining groups R.sup.1, R.sup.2, R.sup.3 and R.sup.4 is a group -AlkCO.sub.2 H or -AlkCONR.sup.6 R.sup.7, or a salt thereof, for use as contrast agents in nuclear magnetic resonance imaging are described.

Tetra-aza macrocycles, processes for their preparation and their use in

Peptidyl derivatives and their use as metalloproteinases inhibitors

Triaza macrocycles carrying a -CH.sub.2 COOH, -CH.sub.2 CONR.sup.6 R.sup.7, --CH.sub.2 P(R.sup.5)O.sub.2 H, or --CH.sub.2 PO.sub.3 H.sub.2 group on two of the three ring nitrogen atoms and a --CH(L--Z)COOH, --CH(L--Z)CONR.sup.6 R.sup.7, --CH(L--Z)P(R.sup.5)O.sub.2 H, or --CH(L--Z)PO.sub.3 H.sub.2 group on the third ring nitrogen atom, in which L is an organic linking radical and Z is any group capable of reacting with a thiol, amino, carboxy, hydroxyl, aldehyde, aromatic, or heteroaromatic group, and metal complexes thereof, are useful for imaging, diagnosis, and therapy. A typical embodiment is N-[5-carboxy-5-{4,7-bis-(carboxymethyl)-1,4,7-triazacyclonon-1-yl}pentyl] 3-maleimidopropionamide.

Triaza macrocycles

Phenylaminocarbonyl derivatives

N-sulphonylamino derivatives of dipetide compounds as metalloproteinase

##STR1## Compounds of formula (1) are described wherein Y represents a halogen atom or a group --OR.sup.1 where R.sup.1 represents an optionally substituted alkyl group; R.sup.2 represents an optionally substituted cycloalkylcycloalkenyl or polycycloalkyl group; R.sup.3 represents a hydrogen atom or an alkyl, aryl or aralkyl group; R.sup.4 represents an aryl or heteroaryl group; X represents --O--, --S--, --CH.sub.2 -- or --N(R.sup.5)--, where R.sup.5 is a hydrogen atom or an alkyl group; n is zero or an integer or value 1, 2 or 3; and the salts, solvates and hydrates thereof. The compounds are selective phosphodiesterase IV inhibitors and are useful for the prophylaxis or treatment of inflammatory diseases.

Growing community of inventors

Thame, United Kingdom

Nigel Robert Beeley