US 4,307,116 A · 3-Thiovinyl-cephalosporins

Abstract

Novel cephalosporins of the general formula (I); ##STR1## in which R is alkyl, L-2-amino-2-carboxy-ethyl, phenyl, pyridyl, pyridyl-N-oxide, pyrimidin-2-yl, substituted pyridazin-3-yl, 5,6-dioxo-1,4,5,6-tetrahydro-1,2,4-triazin-3-yl substituted in the 4-position, 1,3,4-triazol-5-yl or 2-alkoxycarbonyl-1,3,4-triazol-5-yl substituted in the 1-position, 1,4-dialkyl-5,6-dioxo-1,4,5,6-tetrahydro-1,2,4-triazin-3-yl, 1-alkyl-5,6-dioxo-1,4,5,6-tetrahydro-1,2,4-triazin-3-yl, 2-alkyl-5,6-dioxo-1,2,5,6-tetrahydro-1,2,4-triazin-3-yl, triazol-5-yl, 1,3,4-thiadiazol-5-yl which is substituted or unsubstituted, 1,2,4-thiadiazol-5-yl which is substituted, 1,3,4-oxadiazol-5-yl which is substituted or unsubstituted, oxazol-2-yl which is substituted or unsubstituted or tetrazol-5-yl which is substituted or unsubstituted in the 1-position, R' is a hydrogen atom or a radical of the general formula (II); ##STR2## and R.sup.o is hydrogen, alkyl, vinyl or cyanomethyl, as well as their salts, are useful as anti-bacterial agents.

A 3-thiovinyl-cephalosporin which corresponds to the general formula:

##STR134## in which the symbol R is chosen from amongst the following meanings:
(1) alkyl, L-2-amino-2-carboxy-ethyl and phenyl,
(2) pyrid-2-yl, pyrid-3-yl or pyrid-4-yl and their N-oxides,
(3) pyrimidin-2-yl;
pyridazin-3-yl substituted in the 6-position (by an alkyl, methoxy, amino or acylamino radical), its N-oxide, and tetrazolo[4,5-b]pyridazin-6-yl,
(4) 5,6-dioxo-1,4,5,6-tetrahydro-1,2,4-triazin-3-yl substituted in the 4-position;
1,3,4-triazol-5-yl or 2-alkoxycarbonyl-1,3,4-triazol-5-yl, in each case substituted in the 1-position
(a) by an alkyl radical which is unsubstituted or substituted by an alkoxy, alkylthio, phenyl, formyl, carbamyl, alkylcarbamyl, dialkylcarbamyl, acyl, alkoxycarbonyl or thiazolidin-2-yl radical,
(b) by an allyl, 2,3-dihydroxypropyl, 1,3-dihydroxyprop-2-yl, 2-formyl-2-hydroxy-ethyl, 3-formyloxy-2-hydroxypropyl, 2,3-bisformyloxypropyl, or 1,3-bisformyloxyprop-2-yl radical,
(c) by an alkyl radical which contains 2 to 4 carbon atoms and is substituted by a hydroxyl, carbamyloxy, acyloxy (of which the acyl part can be substituted by an amino, alkylamino or dialkylamino radical), alkylsulphinyl, alkylsulphonyl, amino, alkylamino, dialkylamino, sulphoamino, alkylsulphonylamino, sulphamylamino, acylamino (of which the acyl part is optionally substituted by hydroxyl, amino, alkylamino or dialkylamino), alkoxycarbonylamino, ureido, alkylureido or dialkylureido radical,
(d) by a radical corresponding to one of the general formulae:
##STR135## in which alk is an alkylene radical containing 1 to 4 carbon atoms, X.sup..alpha. and Y.sup..alpha. are identical and represent oxygen or sulphur atoms and R.sup..alpha. represents an alkyl radical, or X.sup..alpha. and Y.sup..alpha. are identical or different and represent oxygen or sulphur atoms and the radicals R.sup..alpha. together form an alkylene radical containing 2 or 3 carbon atoms, and R.sup..beta. represents a hydrogen atom or an alkyl radical containing 1 to 3 carbon atoms, or
(e) by an alkyl radical containing 1 to 5 carbon atoms, substituted by an alkoxyimino or hydroxyimino radical,
(5) 1,4-dialkyl-5,6-dioxo-1,4,5,6-tetrahydro-1,2,4-triazin-3-yl, 1-alkyl-5,6-dioxo-1,4,5,6-tetrahydro-1,2,4-triazin-3-yl or 2-alkyl-5,6-dioxo-1,2,5,6-tetrahydro-1,2,4-triazin-3-yl,
(6) 1,3,4-triazol-5-yl, 1,2,3-triazol-5-yl or 1-alkyl-1,2,4-triazol-5-yl, which is unsubstituted or substituted in the 3-position by alkoxycarbonyl,
(7a) 1,3,4-thiadiazol-5-yl which is unsubstituted or substituted by an alkyl, trifluoromethyl, alkoxy, alkylthio, hydroxyalkylthio, of which the alkyl part contains 2 to 4 carbon atoms, alkylsulphonyl, hydroxyl, hydroxyalkyl, carboxyl, carboxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, acylamino or acylaminoalkyl radical, or
(b) 1,2,4-thiadiazol-5-yl substituted by an alkyl or alkoxy radical,
(8a) 1,3,4-oxadiazol-5-yl which is unsubstituted or substituted by an alkyl, trifluoromethyl, phenyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl or acylaminoalkyl radical, or
(b) oxazol-2-yl or 4-alkyl-oxazol-2-yl, or
(9) tetrazol-5-yl which is unsubstituted or substituted in the 1-position by
(a) an alkyl radical which is unsubstituted or substituted by alkoxy, sulpho, carboxyl, formyl or sulphamyl,
(b) an alkyl radical which contains 2 to 4 carbon atoms and is substituted by hydroxyl, amino, alkylamino, dialkylamino, acylamino, carboxyalkylamino, sulphamylamino, sulphonylamino, ureido, alkylureido or dialkylureido,
(c) an alkyl radical which contains 1 to 5 carbon atoms and is substituted by hydroxyimino or alkoxyimino,
(d) a phenyl, 2,3-dihydroxypropyl, 1,3-dihydroxyprop-2-yl, 2-formyl-2-hydroxy-ethyl, 3-formyloxy-2-hydroxypropyl, 2,3-bisformyloxy-propyl, or 1,3-bisformyloxy-prop-2-yl radical or
(e) a radical of the general formula (II), in which R.sup..beta. is a hydrogen atom or a radical of the general formula (III), the symbol R.sup.o represents a hydrogen atom or an alkyl, vinyl or cyanomethyl radical, and the symbol R' represents a hydrogen atom or an enzymatically easily removable radical of the general formula:
##STR136## in which R" represents a hydrogen atom or an alkyl radical and R"' represents an alkyl radical or the cyclohexyl radical, it being understood that the alkyl or acyl portions or radicals mentioned above are (unless stated to the contrary) straight or branched and contain 1 to 4 carbon atoms,
in its syn- or anti- and E- or Z-forms, and in the form of mixtures of these, as well as its addition salts with acids, its metal salts and its addition salts with nitrogen-containing bases.

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3-Thiovinyl-cephalosporins

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3-Thiovinyl-cephalosporins

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Abstract

Claims14