1-Carbacephalosporin antibiotics

A compound of the formula ##STR174## wherein R is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 cyano, carboxy, halogen, amino, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkylthio, or trifluoromethylthio;

• a phenyl or substituted phenyl group of the formula ##STR175## wherein a and a' independently are hydrogen, halogen, hydroxy, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkanyloxy, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkylthio, amino, C.sub.1 -C.sub.4 alkanoylamino, C.sub.1 -C.sub.4 alkylsulfonylamino, carboxy, carbamoyl, hydroxymethyl, aminomethyl, or carboxymethyl;
• or a group of the formula ##STR176## wherein a and a' have the same meanings as defined above, Z is O or S, and m is 0 or 1;
• or a heteroarylmethyl group of the formula R.sup.1 --CH.sub.2 -- wherein R.sup.1 is thienyl, furyl, benzothienyl, benzofuryl, pyridyl, 4-pyridylthio, pyrimidyl, pyridazinyl, indolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, thiazolyl, oxadiazolyl, thiadiazolyl, and said heteroaryl groups mono-substituted by amino, hydroxy, halogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, or C.sub.1 -C.sub.4 alkylsulfonylamino;
• or a substituted methyl group of the formula ##STR177## wherein R.sup.2 is cyclohex-1,4-dienyl, or a phenyl group of the formula ##STR178## as defined above, or R.sup.2 is R.sup.1 as defined above, and Q is hydroxy, C.sub.1 -C.sub.4 alkanoyloxy, carboxy, sulfo, amino, sulfoamino, or a substituted amino group of the formula ##STR179## wherein R.sup.x is hydrogen or C.sub.1 -C.sub.3 alkyl, R.sup.y is C.sub.1 -C.sub.4 alkyl, furyl, thienyl, phenyl, halophenyl, nitrophenyl, styryl, halostyryl, nitrostyryl or a group of the formula ##STR180## wherein R.sup.x has the same meanings as defined above and R.sup.z is hydrogen, C.sub.1 -C.sub.3 alkylsulfonyl, C.sub.1 -C.sub.3 alkyl, or C.sub.1 -C.sub.4 alkanoyl;
• or Q is a substituted amino group of the formula ##STR181## wherein R.sup.z has the same meanings as defined above, and q is 2 or 3;
• or Q is a substituted amino group of the formula ##STR182## a benzamido group ##STR183## wherein t is 1 to 3;
• a pyridone group ##STR184## a pyridyl group ##STR185## and said pyridyl group mono-substituted by C.sub.1 -C.sub.4 alkyl, amino, carboxy, hydroxy or halogen;
• an imidazolyl or pyrazolyl group ##STR186## and said imidazolyl or pyrazolyl mono-substituted by C.sub.1 -C.sub.4 alkyl, carboxy, amino, or halogen;
• a benzpyridazin-4-one group or tautomer thereof ##STR187## wherein z is hydrogen or C.sub.1 -C.sub.3 alkyl, and t is 1 to 3;
• or a benzpyranone group ##STR188## or R is a keto group or an oximino-substituted group of the formulae ##STR189## wherein R.sup.3 is R.sup.1 or R.sup.2 as defined above and R.sup.4 is hydrogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkyl substituted by halogen, a carboxy-substituted alkyl or cycloalkyl group represented by the formula ##STR190## wherein b and b' independently are hydrogen, or C.sub.1 -C.sub.3 alkyl, n is 0, 1, 2, or 3;
• and b and b' when taken together with the carbon to which they are bonded form a 3- to 6-membered carbocyclic ring, and R.sup.5 is hydroxy, C.sub.1 -C.sub.4 alkoxy, amino, C.sub.1 -C.sub.4 alkylamino, or di(C.sub.1 -C.sub.4 alkyl)amino;
• or R.sub.4 is C.sub.1 -C.sub.4 substituted by phenyl or phenyl substituted by one or two of the same or different groups selected from among C.sub.1 -C.sub.4 alkyl, hydroxy, halogen, carboxy or protected carboxy;
• or R.sub.4 is C.sub.1 -C.sub.4 alkyl substituted by amino or protected amino;
• or R.sub.4 is C.sub.2 -C.sub.4 alkenyl;
• or R.sub.4 is a cyclic lactam group of the formula ##STR191## wherein v is 2-4 and R.sup.6 is hydrogen or C.sub.1 -C.sub.3 alkyl;
• or R.sup.4 is a heteroaryl group
• R.sup.1 --CH.sub.2 --
• wherein
• R.sup.1 has the same meanings as defined hereinabove;
• R.sub.1 is hydrogen, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkylthio;
• or formamido;
• R.sub.2 is hydrogen, a carboxy-protecting group, or a biologically labile ester;
• A is hydroxy, halo, azido, 2-(tri-C.sub.1 -C.sub.4 alkylsilyl)ethoxy, C.sub.1 -C.sub.6 alkoxy, C.sub.2 -C.sub.6 alkenyloxy, C.sub.2 -C.sub.6 alkinyloxy, C.sub.1 -C.sub.4 alkoxycarbonyloxy, phenoxy, or phenoxy substituted by one or two of the same or different groups selected from C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, methylenedioxy, halo, hydroxy, amino, C.sub.1 -C.sub.4 alkylamino, di-(C.sub.1 -C.sub.4 alkyl)amino, C.sub.1 -C.sub.4 alkanoylamino, carboxy, carbamoyl, cyano, trifluoromethyl, or C.sub.1 -C.sub.4 alkanoyl;
• or C.sub.1 -C.sub.6 alkoxy substituted by one or two of the same or different groups selected from among hydroxy, amino, C.sub.1 -C.sub.4 alkylamino, di(C.sub.1 -C.sub.4 alkyl)amino, C.sub.1 -C.sub.4 alkanoylamino, halo, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkylthio, cyano, carboxy, C.sub.1 -C.sub.4 alkoxycarbonyl, carbamoyl, carbamoyloxy, N-(C.sub.1 -C.sub.4 alkyl)carbamoyloxy, N,N-di-(C.sub.1 -C.sub.4 alkyl)carbamoyloxy, C.sub.1 -C.sub.4 alkoxycarbonyloxy, phenoxycarbonyloxy, C.sub.1 -C.sub.4 alkoxycarbonylamino, phenoxycarbonylamino, N-(C.sub.1 -C.sub.4 alkyl)carbamoylamino, N,N-di-(C.sub.1 -C.sub.4 alkyl)carbamoylamino, N-phenylcarbamoylamino, anilino, substituted anilino, phenyl, substituted phenyl, where said substituted anilino and substituted phenyl groups are substituted on the phenyl ring by one or two of the same or different groups selected from among C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkyloxy, methlenedioxy, halo, hydroxy, amino, C.sub.1 -C.sub.4 alkylamino, di-(C.sub.1 -C.sub.4 alkyl)amino, C.sub.1 -C.sub.4 alkanoylamino, carboxy, carbamoyl, cyano, trifluoromethyl, or C.sub.1 -C.sub.4 alkanoyl;
• or a heterocyclic amino group R.sub.3 NH-- wherein R.sub.3 is thienyl, furyl or a 5-membered nitrogen containing heterocyclic ring represented by the formulae ##STR192## wherein R.sub.3 ' is hydrogen, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkyl substituted by carboxy, sulfo, or di(C.sub.1 -C.sub.4 alkyl)amino;
• or R.sub.3 is a 6-membered nitrogen-containing ring represented by the formulae ##STR193## wherein R.sub.3 " is hydrogen or C.sub.1 -C.sub.4 alkyl;
• or a thio group R.sub.3.sup.o S-- wherein R.sub.3.sup.o is phenyl, substituted phenyl as defined above or R.sub.3 as defined above;
• or a quaternary heterocyclic group R.sub.4.sup.o.sym. X.sup..crclbar. wherein R.sub.4.sup.o.sym. is a nitrogen containing heterocyclic represented by the formulae ##STR194## wherein R.sub.4 ' is C.sub.1 -C.sub.4 alkyl, benzyl, or --CH.sub.2 COCH.sub.3, and X.sup..crclbar. is a halide, sulfate, or nitrate anion;
• or R.sub.4.sup.o.sym. --S--X.sup..crclbar. wherein R.sub.4.sup.o.sym. and X.sup..crclbar. are as defined above;
• or C.sub.1 -C.sub.6 alkoxy substituted by a heterocyclic group R.sub.3 as defined above;
• or A is an amino group represented by the formula
• --N(R')(R")
• wherein R' and R" are independently hydrogen, phenyl, substituted phenyl as defined above, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkyl substituted by one or two of the same or different groups selected from among halo, hydroxy, C.sub.1 -C.sub.4 alkanoyloxy, C.sub.1 -C.sub.4 alkylsulfonyloxy, amino, or C.sub.1 -C.sub.4 alkanoylamino;
• or R' and R" can be taken together with the nitrogen atom to which they are bonded to form a 5-7 membered ring represented by the formula ##STR195## wherein Y is --CH.sub.2 --.sub.p or --CH.sub.2 --Y'--CH.sub.2 -- wherein p is 2-4 and Y' is O, S, or NR'" wherein R'" is hydrogen or C.sub.1 -C.sub.4 alkyl;
• or R' is hydrogen and R" is C.sub.1 -C.sub.4 alkyl substituted by a heterocyclic R.sub.3, or a heterocyclic amino group R.sub.3 NH--, or a thio group R.sub.3.sup.o S--, or a quaternary heterocyclic group R.sub.4.sup.o.sym. X.sup..crclbar., wherein R.sub.3, R.sub.3.sup.o, R.sub.4.sup.o.sym. and X.sup..crclbar. have the same meanings as defined above;
• or A is a heterocyclic amino group R.sub.3 NH-- wherein R.sub.3 is as defined above, phenyl, or substituted phenyl as defined above;
• or A is C.sub.1 -C.sub.4 alkyl, or C.sub.1 -C.sub.4 alkyl monosubstituted by hydroxy, C.sub.1 -C.sub.4 alkanoyloxy, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkylthio, halogen, carboxy, cyano, amino, C.sub.1 -C.sub.4 alkylamino, di-(C.sub.1 -C.sub.4 alkyl)amino, C.sub.1 -C.sub.4 alkanoylamino, C.sub.1 -C.sub.4 alkylsulfonylamino, C.sub.1 -C.sub.4 alkylsulfonyloxy, phenyl, substituted phenyl as defined above, phenoxy, substituted phenoxy as defined above, anilino, substituted anilino as defined above, a heterocyclic group R.sub.3, a heterocyclic amino group R.sub.3 NH, a thio group R.sub.3.sup.o S--, or a quaternary heterocyclic group R.sub.4.sup.o.sym. X.sup..crclbar. or R.sub.4.sup.o.sym. --S--X.sup..crclbar., wherein R.sub.3, R.sub.3.sup.o, R.sub.4.sup.o.sym., and X.sup..crclbar. are as defined above;
• or A is phenyl, thienyl, furyl, pyridyl, pyrimidyl, imidazolyl, pyrazolyl, tetrazolyl, oxazolyl, thiazolyl, thiadiazolyl or oxadiazolyl, and said phenyl or heterocycle substituted by one or two of the same or different substituents selected from C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halogen, amino, or hydroxy;
• or A is a group of the formula --COR.sub.6 wherein R.sub.6 is hydrogen, hydroxy, C.sub.1 -C.sub.4 alkoxy, phenoxy, substituted phenoxy as defined above, tri-(C.sub.1 -C.sub.4 alkyl)silyloxy, amino, C.sub.1 -C.sub.4 alkylamino, di-(C.sub.1 -C.sub.4 alkyl)amino, phenyl, substituted phenyl as defined above, or C.sub.1 -C.sub.4 alkyl;
• or A is the group --CH.sub.2 --.sup..sym. R.sub.4 wherein .sup..sym. R.sub.4 is pyridinium, or a substituted pyridinium group substituted by one or two of the same or different groups selected from among C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkylthio, hydroxy, halogen, trifluoromethyl, cyano, carboxy, carbamoyl, amino, or C.sub.1 -C.sub.4 alkoxycarbonyl;
• or the pyridinium ring is substituted on adjacent carbon atoms with a divalent alkylene group represented by the formula --CH.sub.2 --.sub.p' wherein p' is 3-5, or the divalent alkylene group is interrupted by an O, S, or one or two N atoms and in addition can contain one or two double bonds and can be substituted in either ring by one or two of the same or different substituents selected from the groups defined above when .sup..sym. R.sub.4 is a substituted pyridine;
• or .sup..sym. R.sub.4 is a thiazolium ring or a substituted thiazolium ring substituted by one or two of the same or different groups, amino, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkylthio, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkyl substituted by hydroxy, C.sub.1 -C.sub.4 alkanoyloxy, C.sub.1 -C.sub.4 alkylsulfonyloxy, halogen, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkylthio, or amino, or the thiazolium ring is substituted on the adjacent carbon atoms with a divalent alkylene group represented by the formula --CH.sub.2 --.sub.p' wherein p' is 3-5;
• and when R.sub.2 is hydrogen, the pharmaceutically acceptable non-toxic salts and biologically labile esters thereof.