.beta.-lactam compounds

A compound of the formula ##STR25## in which Z signifies oxygen or sulphur, A signifies lower alkyl, hydroxy-lower alkyl, vinyl, cyanovinyl, optionally phenyl-substituted lower (cyclo)alkanoyloxy or (cyclo)alkylsulphonyloxy, optionally lower-(cyclo)alkyl-substituted benzoyloxy or phenylsulphonyloxy, a residue --S-Het or --S--CH.sub.2 -Het, wherein Het represents a 5- or 6-membered heterocycle containing nitrogen, sulphur and/or oxygen, or a residue --CH.sub.2 -L, wherein L represents optionally phenyl-substituted lower (cyclo)alkanoyloxy or (cyclo)alkylsulphonyloxy, optionally lower (cyclo)alkyl-substituted benzoyloxy or phenylsulphonyloxy, carbamoyloxy, lower (cyclo)alkoxycarbonyl, carboxy, azido, amino, lower (cyclo)alkanoylamino, lower (cyclo)alkylsulphonylamino, lower (cyclo)alkylamino, di-lower (cyclo)aikylamino, a 5- or 6-membered ring bonded to a nitrogen atom or a residue --S-Het or --S--CH.sub.2 -Het, wherein Het has the above significance, R.sup.S signifies an amino protecting group or hydrogen, lower (cyclo)alkyl optionally substituted by carboxy, lower alkoxycarbonyl, carbamoyl, lower alkylcarbamoyl, phenylcarbamoyl or hydroxyphenylcarbamoyl, lower alkenylmethyl, lower alkenylmethoxycarbonyl, formyl, lower (cyclo)alkanoyl or (cyclo)alkylsulphonyl optionally substituted by halogen, cyano, carbamoyl-lower-alkoxy, carbamoyl-lower alkylthio or carbamoyl-lower alkylamino, carbamoyl optionally substituted by lower (cyclo)alkyl, lower alkoxycarbonyl-lower alkyl, benzyloxycarbonyl-lower alkyl or carboxy-lower alkyl or a ring structure of the formulae

• Q--X--CO-- (a1)
• Q--X--SO.sub.2 (a 2)
• wherein Q represents a 5- or 6-membered ring optionally containing nitrogen, sulphur and/or oxygen and X represents a direct bond or one of the groups --CH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, --NH--, --NHCH.sub.2 --, --CH.sub.2 NH--, --CH(NH.sub.2)--, --CH.sub.2 CH.sub.2 NH--, --C(.dbd.NOCH.sub.3)--, --OCH.sub.2 - and --SCH.sub.2 -- and R.sup.S2 represents a carboxy protecting group.

A pharmaceutical composition comprising a therapeutically effective amount of a compound of the formula ##STR27## in which Z signifies oxygen or sulphur and R signifies hydrogen, lower (cyclo)alkyl optionally substituted by carboxy, lower alkoxycarbonyl, carbamoyl, lower alkylcarbamoyl, phenylcarbamoyl or hydroxyphenylcarbamoyl, lower alkenylmethyl, lower alkenylmethoxycarbonyl, formyl, lower (cyclo)alkanoyl or (cyclo)alkylsulphonyl optionally substituted by halogen, cyano, carbamoyl-lower-alkoxy, carbamoyl-lower alkylthio or carbamoyl-lower alkylamino, carbamoyl optionally substituted by lower (cyclo)alkyl, lower alkoxycarbonyl-lower alkyl, benzyloxycarbonyl-lower alkyl or carboxy-lower alkyl or a ring structure of the formulae

• Q--X--CO-- (a1)
• Q--X--SO.sub.2 -- (a2)
• wherein Q represents a 5- or 6-membered ring optionally containing nitrogen, sulphur and/or oxygen and X represents a direct bond or one of the groups --CH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, --NH--, --NHCH.sub.2 --, --CH.sub.2 NH--, --CH(NH.sub.2)--, --CH.sub.2 CH.sub.2 NH--, --C(.dbd.NOCH.sub.3)--, --OCH.sub.2 -- and --SCH.sub.2 --;
• and wherein further A signifies lower alkyl, hydroxy-lower alkyl, vinyl, cyanovinyl, lower alkoxy, optionally phenyl-substituted lower (cyclo)alkanoyloxy or (cyclo)alkylsulphonyloxy, optionally lower-(cyclo)alkyl-substituted benzoyloxy or phenylsulphonyloxy, a residue --S-Het or --S--CH.sub.2 -Het, wherein Het represents a 5- or 6-membered heterocycle containing nitrogen, sulphur and/or oxygen, or a residue --CH.sub.2 -L, wherein L represents optionally phenyl-substituted lower (cyclo)alkanoyloxy or (cyclo)alkylsulphonyloxy, optionally lower (cyclo)alkyl-substituted benzoyloxy or phenylsulphonyloxy, carbamoyloxy, lower (cyclo)alkoxycarbonyl, carboxy, azido, amino, lower (cyclo)alkanoylamino, lower (cyclo)alkylsulphonylamino, lower (cyclo)alkylamino, di-lower (cyclo)alkylamino, a 5- or 6-membered ring bonded to a nitrogen atom or a residue --S-Het or --S--CH.sub.2 -Het, wherein Het has the above significance, or a pharmaceutically compatible, readily hydrolyzable ester or salt of one of these compounds, and a pharmaceutically acceptable carrier.

A pharmaceutical composition comprising

• (a) a therapeutically effective mount of a compound of the formula ##STR28## in which Z signifies oxygen or sulphur and R signifies hydrogen, lower (cyclo)alkyl optionally substituted by carboxy, lower alkoxycarbonyl, carbamoyl, lower alkylcarbamoyl, phenylcarbamoyl or hydroxyphenylcarbamoyl, lower alkenylmethyl, lower alkenylmethoxycarbonyl, formyl, lower (cyclo)alkanoyl or (cyclo)alkylsulphonyl optionally substituted by halogen, cyano, carbamoyl-lower-alkoxy, carbamoyl-lower alkylthio or carbamoyl-lower alkylamino, carbamoyl optionally substituted by lower (cyclo)alkyl, lower alkoxycarbonyl-lower alkyl, benzyloxycarbonyl-lower alkyl or carboxy-lower alkyl or a ring structure of the formulae
• --Q--X--CO-- (a1)
• --Q--X--SO.sub.2 -- (a2)
• wherein Q represents a 5- or 6-membered ring optionally containing nitrogen, sulphur and/or oxygen and X represents a direct bond or one of the groups --CH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, --NH--, --NHCH.sub.2 --, --CH.sub.2 NH--, --CH(NH.sub.2)--, --CH.sub.2 CH.sub.2 NH--, --C(.dbd.NOCH.sub.3)--, --OCH.sub.2 -- and --SCH.sub.2 --;
• and wherein further A signifies lower alkyl, hydroxy-lower alkyl, vinyl, cyanovinyl, lower alkoxy, optionally phenyl-substituted lower (cyclo)alkanoyloxy or (cyclo)alkylsulphonyloxy, optionally lower-(cyclo) alkyl-substituted benzoyloxy or phenylsulphonyloxy, a residue --S-Het or --S--CH.sub.2 -Het, wherein Het represents a 5- or 6-membered heterocycle containing nitrogen, sulphur and/or oxygen, or a residue --CH.sub.2 -L, wherein L represents optionally phenyl-substituted lower (cyclo)alkanoyloxy or (cyclo)alkylsulphonyloxy, optionally lower (cyclo)alkyl-substituted benzoyloxy or phenylsulphonyloxy, carbamoyloxy, lower (cyclo)alkoxycarbonyl, carboxy, azido, amino, lower (cyclo)alkanoylamino, lower (cyclo)alkylsulphonylamino, lower (cyclo)alkylamino, di-lower (cyclo)alkylamino, a 5- or 6-membered ring bonded to a nitrogen atom or a residue --S-Het or --S--CH.sub.2 -Het, wherein Het has the above significance,
• or a pharmaceutically compatible, readily hydrolyzable ester or salt of one of these compounds;
• and
• (b) a .beta.-lactam antibiotic or a pharmaceutically acceptable salt thereof;
• and a pharmaceutically acceptable carrier.

A method of treating bacterial infections in a mammal in need of such treatment which comprises administering a therapeutically effective mount of a compound of the formula ##STR29## in which Z signifies oxygen or sulphur and R signifies hydrogen, lower (cyclo)alkyl optionally substituted by carboxy, lower alkoxycarbonyl, carbamoyl, lower alkylcarbamoyl, phenylcarbamoyl or hydroxyphenylcarbamoyl, lower alkenylmethyl, lower alkenylmethoxycarbonyl, formyl, lower (cyclo)alkanoyl or (cyclo)alkylsulphonyl optionally substituted by halogen, cyano, carbamoyl-lower-alkoxy, carbamoyl-lower alkylthio or carbamoyl-lower alkylamino, carbamoyl optionally substituted by lower (cyclo)alkyl, lower alkoxycarbonyl-lower alkyl, benzyloxycarbonyl-lower alkyl or carboxy-lower alkyl or a ring structure of the formulae

• Q--X--CO-- (a1)
• Q--X--SO.sub.2 -- (a2)
• wherein Q represents a 5- or 6-membered ring optionally containing nitrogen, sulphur and/or oxygen and X represents a direct bond or one of the groups --CH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, --NH--, --NHCH.sub.2 --, --CH.sub.2 NH--,--CH(NH.sub.2)--, --CH.sub.2 CH.sub.2 NH--, --C(.dbd.NOCH.sub.3)--, --OCH.sub.2 -- and --SCH.sub.2 --;
• and wherein further A signifies lower alkyl, hydroxy-lower alkyl, vinyl, cyanovinyl, lower alkoxy, optionally phenyl-substituted lower (cyclo)alkanoyloxy or (cyclo)alkylsulphonyloxy, optionally lower-(cyclo)alkyl-substituted benzoyloxy or phenylsulphonyloxy, a residue --S-Het or --S--CH.sub.2 -Het, wherein Het represents a 5- or 6-membered heterocycle containing nitrogen, sulphur and/or oxygen, or a residue --CH.sub.2 -L, wherein L represents optionally phenyl-substituted lower (cyclo)alkanoyloxy or (cyclo)alkylsulphonyloxy, optionally lower (cyclo)alkyl-substituted benzoyloxy or phenylsulphonyloxy, carbamoyloxy, lower (cyclo)alkoxycarbonyl, carboxy, azido, amino, lower (cyclo)alkanoylamino, lower (cyclo)alkylsulphonylamino, lower (cyclo)alkylamino, di-lower (cyclo)alkylamino, a 5- or 6-membered ring bonded to a nitrogen atom or a residue --S-Het or --S--CH.sub.2 -Het, wherein Het has the above significance, or a pharmaceutically compatible, readily hydrolyzable ester or salt of one of these compounds;
• and a pharmaceutically acceptable carrier.

A method of treating bacterial infection in a mammal in need of such treatment comprising administering

• (a) a therapeutically effective mount of a compound of the formula ##STR30## in which Z signifies oxygen or sulphur and R signifies hydrogen, lower (cyclo)alkyl optionally substituted by carboxy, lower alkoxycarbonyl, carbamoyl, lower alkylcarbamoyl, phenylcarbamoyl or hydroxyphenylcarbamoyl, lower alkenylmethyl, lower alkenylmethoxycarbonyl, formyl, lower (cyclo)alkanoyl or (cyclo)alkylsulphonyl optionally substituted by halogen, cyano, carbamoyl-lower-alkoxy, carbamoyl-lower alkylthio or carbamoyl-lower alkylamino, carbamoyl optionally substituted by lower (cyclo)alkyl, lower alkoxycarbonyl-lower alkyl, benzyloxycarbonyl-lower alkyl or carboxy-lower alkyl or a ring structure of the formulae
• Q--X--CO-- (a1)
• Q--X--SO.sub.2 -- (a2)
• wherein Q represents a 5- or 6-membered ring optionally containing nitrogen, sulphur and/or oxygen and X represents a direct bond or one of the groups --CH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, --NH--, --NHCH.sub.2 --, --CH.sub.2 NH--, --CH(NH.sub.2)--, --CH.sub.2 CH.sub.2 NH--, --C(.dbd.NOCH.sub.3)--, --OCH.sub.2 -- and --SCH.sub.2 --;
• and wherein further A signifies lower alkyl, hydroxy-lower alkyl, vinyl, cyanovinyl, lower alkoxy, optionally phenyl-substituted lower (cyclo)alkanoyloxy or (cyclo)alkylsulphonyloxy, optionally lower-(cyclo)alkyl-substituted benzoyloxy or phenylsulphonyloxy, a residue --S-Het or --S--CH.sub.2 -Het, wherein Het represents a 5- or 6-membered heterocycle containing nitrogen, sulphur and/or oxygen, or a residue --CH.sub.2 -L, wherein L represents optionally phenyl-substituted lower (cyclo)alkanoyloxy or (cyclo)alkylsulphonyloxy, optionally lower (cyclo)alkyl-substituted benzoyloxy or phenylsulphonyloxy, carbamoyloxy, lower (cyclo)alkoxycarbonyl, carboxy, azido, amino, lower (cyclo)alkanoylamino, lower (cyclo)alkylsulphonylamino, lower (cyclo)alkylamino, di-lower (cyclo)alkylamino, a 5- or 6-membered ring bonded to a nitrogen atom or a residue --S-Het or --S--CH.sub.2 -Het, wherein Het has the above significance, or a pharmaceutically compatible, readily hydrolyzable ester or salt of one of these compounds:
• and
• (b) a .beta.-lactam antibiotic or a pharmaceutically acceptable salt thereof;
• and a pharmaceutically acceptable carrier.