Peptidyl derivatives

A method for reducing tumor colonization, comprising administering to a patient suspected of having a lung tumor an amount of a pharmaceutical composition effective for reducing gelatinase-dependent colonization of said lung tumor,

• wherein said pharmaceutical composition comprises a pharmaceutically acceptable diluent, carrier or excipient, and a compound of formula (I):
• ##STR21## wherein R represents a --CONHOH or carboxyl group;
• R.sup.1 represents a hydrogen atom or an unsubstituted or substituted straight or branched C.sub.6-12 -alkyl, C.sub.6-12 -alkenyl, phenyl, .alpha.-naphthyl, .beta.-naphthyl, phenylC.sub.1-6 -alkyl, .alpha.-naphthylC.sub.1-6 -alkyl, .beta.-naphthylC.sub.1-6 -alkyl, pyrrolylmethyl, pyrrolylthiomethyl, furanylmethyl, furanylthiomethyl, thienylmethyl, imidazolylmethyl, oxazolylmethyl, oxazolylthiomethyl, thiazolylmethyl, thiazolylthiomethyl, pyrazolylmethyl, pyrrolidinylmethyl, pyrrolidinylthiomethyl, pyridinylmethyl, pyridinylthiomethyl, pyrimidinylmethyl, pyriminylthiomethyl, morpholinylmethyl, morpholinylthiomethyl, piperizinylmethyl or piperizinylthiomethyl group;
• R.sup.2 represents an unsubstituted phenylethyl, phenylpropyl or phenylbutyl group, or a substituted phenylethyl, phenylpropyl or phenylbutyl substituted in the cyclic portion of the group by one or more substituents selected from the group consisting of halogen atoms, C.sub.1-6 -alkyl, C.sub.1-6 -alkoxy, C.sub.1-6 -alkylenedioxy, haloC.sub.1-6 -alkyl, C.sub.1-6 -alkylamino, C.sub.1-6 -dialkylamino, amino (--NH.sub.2), nitro, cyano, hydroxyl (--OH), carboxyl (--CO.sub.2 H), CO.sub.2 R.sup.8, C.sub.1-6 -alkylcarbonyl, sulphonyl (--SO.sub.3 H), C.sub.1-6 -alkylaminosulphonyl, C.sub.1-6 -dialkylaminosulphonyl, carboxamido (--CONH.sub.2), C.sub.1-6 -alkylaminocarbonyl and C.sub.1-6 -dialkylsulphonylamino groups;
• R.sup.3 represents a hydrogen atom or a C.sub.1-6 -alkyl group;
• R.sup.4 represents a hydrogen atom or a C.sub.1-6 -alkyl group;
• R.sup.5 represents an unsubstituted or substituted straight or branched C.sub.1-6 -alkyl or C.sub.1-6 -alkenyl 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 --NR.sup.11 R.sup.12 where R.sup.11 and R.sup.12 are the same or different and represent a hydrogen atom with the proviso that when one of R.sup.11 or R.sup.12 is a hydrogen atom, the other is not, an unsubstitiuted or substituted straight or branched C.sub.1-6 -alkyl optionally interrupted by one or more --O-- or --S-- atoms or --N(R.sup.7), or aminocarbonyloxy groups, or R.sup.11 and R.sup.12, taken together with the nitrogen atom to which they are attached, form an unsubstituted or substituted morpholinyl, imidazolyl, piperizinyl, pyrrolyl, oxazolyl, thiazolyl, pyrazolyl, pyrrolidinyl, pyridinyl, or pyrimidinyl group;
• or a pharmaceutically acceptable salt, or hydrate thereof.

A method for inhibiting a metalloproteinase, comprising contacting a metalloproteinase with an effective inhibiting amount of a compound of formula (I):

• ##STR22## wherein R represents a --CONHOH or carboxyl group;
• R.sup.1 represents a hydrogen atom or an unsubstituted or substituted straight or branched C.sub.6-12 -alkyl, C.sub.6-12 -alkenyl, phenyl, .alpha.-naphthyl, .beta.-naphthyl, phenylC.sub.1-6 -alkyl, .alpha.-naphthylC.sub.1-6 -alkyl, .beta.-naphthylC.sub.1-6 -alkyl, pyrrolylmethyl, pyrrolylthiomethyl, furanylmethyl, furanylthiomethyl, thienylmethyl, imidazolylmethyl, oxazolylmethyl, oxazolylthiomethyl, thiazolylmethyl, thiazolylthiomethyl, pyrazolylmethyl, pyrrolidinylmethyl, pyrrolidinylthiomethyl, pyridinylmethyl, pyridinylthiomethyl, pyrimidinylmethyl, pyriminylthiomethyl, morpholinylmethyl, morpholinylthiomethyl, piperizinylmethyl or piperizinylthiomethyl group;
• R.sup.2 represents an unsubstituted phenylethyl, phenylpropyl or phenylbutyl group, or a substituted phenylethyl, phenylpropyl or phenylbutyl substituted in the cyclic portion of the group by one or more substituents selected from the group consisting of halogen atoms, C.sub.1-6 -alkyl, C.sub.1-6 -alkoxy, C.sub.1-6 -alkylenedioxy, haloC.sub.1-6 -alkyl, C.sub.1-6 -alkylamino, C.sub.1-6 -dialkylamino, amino (--NH.sub.2), nitro, cyano, hydroxyl (--OH), carboxyl (--CO.sub.2 H), CO.sub.2 R.sup.8, C.sub.1-6 -alkylcarbonyl, sulphonyl (--SO.sub.3 H), C.sub.1-6 -alkylaminosulphonyl, C.sub.1-6 -dialkylaminosulphonyl, carboxamido (--CONH.sub.2), C.sub.1-6 -alkylaminocarbonyl and C.sub.1-6 -dialkylsulphonylamino groups;
• R.sup.3 represents a hydrogen atom or a C.sub.1-6 -alkyl group;
• R.sup.4 represents a hydrogen atom or a C.sub.1-6 -alkyl group;
• R.sup.5 represents an unsubstituted or substituted straight or branched C.sub.1-6 -alkyl or C.sub.1-6 -alkenyl 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 --NR.sup.11 R.sup.12 where R.sup.11 and R.sup.12 are the same or different and represent a hydrogen atom with the proviso that when one of R.sup.11 or R.sup.12 is a hydrogen atom, the other is not, an unsubstituted or substituted straight or branched C.sub.1-6 -alkyl optionally interrupted by one or more --O-- or --S-- atoms or --N(R.sup.7), or aminocarbonyloxy groups, or R.sup.11 and R.sup.12, taken together with the nitrogen atom to which they are attached, form an unsubstituted or substituted morpholinyl, imidazolyl, piperizinyl, pyrrolyl, oxazolyl, thiazolyl, pyrazolyl, pyrrolidinyl, pyridinl, or pyrimidinyl group;
• or a pharmaceutically acceptable salt, or hydrate thereof.