Claims
- 1. An antibacterial compound of the formula (I), ##STR601## wherein R is a group represented by the formula ##STR602## each of said moieties A, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 is a conventional cephalosporin substituent selected from the radicals or atoms which each of said moieties represents as set forth subsequently, wherein R.sup.5 represents alkyl, cycloalkyl, cycloalkenyl, cycloalkadienyl, aryl, aralkyl, aryloxy, alkylthioalkyl, furyl, thienyl, oxazoly, thiazolyl, isoxazolyl, isothiazolyl, imidazolyl, pyrazolyl, pyridyl, pyrazyl, pyrimidyl, pyridazyl, quinolyl, isoquinolyl, quinazolyl, indolyl, indazolyl, 1,3,4-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-thiadiazolyl or 1,2,4-thiadiazolyl, any of which may be substituted by halogen, hydroxy, nitro, alkyl, alkoxy, alkylthio, acyl or alkyl-sulfonylamino; R.sup.6 represents a hydrogen atom; and R.sup.5 and R.sup.6 together with a common carbon atom may form a cycloalkyl, cycloalkenyl or cycloalkadienyl ring;
- R.sup.1 represents a hydrogen atom, a blocking group of a conventional cephalosporin or a pharmaceutically acceptable salt-forming cation of a conventional cephalosporin;
- n represents 1 or 2; each of the n X's, which may be identical or different from one another, represents individually an oxygen or sulfur atom, and the n X's are attached in any combination to the 2-, 3-, or 5-positions of the piperazine ring;
- m represents 4-n; each pair of R.sup.2 and R.sup.3 are linked to the same carbon atom, and each R.sup.2 and R.sup.3 of m pairs of R.sup.2 and R.sup.3, which may be the same or different, represent individually hydrogen, halogen, carboxyl, alkyl, cycloalkyl, aryl, acyl, aralkyl, alkoxycarbonylalkyl, acyloxyalkyl, alkoxy, alkoxycarbonyl, cycloalkyloxycarbonyl, aralkoxycarbonyl, aryloxycarbonyl, amino, N-alkylamino, N,N-dialkylamino, N-arylamino, cyclic amino or carbamoyl; any of which may be substituted by halogen, alkyl, alkoxy, alkylthio, acyl or nitro; and any pair of R.sup.2 and R.sup.3 together with a common carbon atom may form a cycloalkyl ring.
- A represents hydrogen, hydroxy, nitro, cyano, alkyl, alkenyl, alkynyl, alkadienyl, cycloalkyl, cycloalkenyl, cycloalkadienyl, aryl, acyl, aralkyl, acyloxyalkyl, alkoxy, cycloalkyloxy, alkoxycarbonyl, aryloxy, cycloalkyloxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkylsulfonyl, cycloalkylsulfonyl, arylsulfonyl, carbamoyl, N-alkylaminocarbonyl, N-arylaminocarbonyl, N,N-dialkylaminocarbonyl, cyclic aminocarbonyl, thiocarbamoyl, N-alkylaminothiocarbonyl, N-arylaminothiocarbonyl, N,N-dialkylaminothiocarbonyl, cyclic aminothiocarbonyl, acylcarbamoyl, acylthiocarbamoyl, alkylsulfonylcarbamoyl, arylsulfonylcarbamoyl, alkylsulfonylthiocarbamoyl, arylsulfonylthiocarbamoyl, sulfamoyl, alkoxycarbonylthioalkyl, alkoxythiocarbonylthioalkyl, amino, N-alkylamino, N,N-diathylomino, N-acylamino, cyclic amino, thiazolyl, pyridyl, pyridazyl, pyrazyl, thiadiazolyl, triazolyl, tetrazolyl or quinolyl, any of which may be substituted by halogen, hydroxyl, alkyl, alkoxy, alkylthio, nitro, cyano, amino, carboxyl, or acyl;
- Y represents an oxygen or sulfur atom; and
- R.sup.4 represents hydrogen, halogen, hydroxy, cyano, azido, pyridinium, quinolinium, isoquinolinium, pyrimidinium, alkoxy, aryloxy, aralkoxy, acyloxy, carbamoyloxy, quanidino, amino, N-alkylamino, N,N-dialkylamino, cyclic amino, alkylthio, arylthio, aralkylthio, acylthio, thiocarbamoylthio, alkoxythiocarbonylthio, aryloxythiocarbonylthio, cycloalkyloxythiocarbonylthio, amidinothio, oxazolylthio, thiazolylthio, isoxazolylthio, isothiazolylthio, imidazolylthio, pyrazolylthio, pyridylthio, pyrazinylthio, pyrimidinylthio, pyridazinylthio, quinolylthio, isoquinolylthio, quinazolylthio, indolylthio, indazolylthio, oxadiazolylthio, thiadiazolylthio, [triazolylthio,] tetrazolylthio, triazinylthio, benzimidazolylthio, benzoxazolylthio, benzothiazolylthio, triazolopyridylthio, purinylthio, pyridine-1-oxide-2-ylthio or pyridazine-1-oxide-6-ylthio each of which may be substituted by halogen, alkyl, nitro, cyano, carboxyl or carbamoyl; thiazolinylthio or 3-(2,6-dimethyl-5-oxo-2,5-dihydro-1,2,4-triazinyl)-thio, with the proviso that when R.sup.4 is pyridinium, quinolinium, isoquinolinium, or pyrimidinium there is present a pharmaceutically acceptable counter-ion.
- 2. An antibacterial compound of claim 1 wherein R.sup.5 represents alkyl, cycloalkadienyl, thienyl, phenyl, p-hydroxy-phenyl; R.sup.6 represents hydrogen; each pair of R.sup.2 and R.sup.3 are linked to the same carbon atom, and each R.sup.2 and R.sup.3 of m pairs of R.sup.2 and R.sup.3, which may be the same or different, represent individually hydrogen, alkyl, aryl or alkoxycarbonylalkyl or any pair of R.sup.2 and R.sup.3 together with a common carbon atom may form a cycloalkyl ring; A represents hydrogen, alkyl, alkenyl, cycloalkyl, aryl, acyl, aralkyl, acyloxyalkyl, alkylsulfonyl, carbamoyl, acylcarbamoyl, N-arylaminocarbonyl or alkoxycarbonyl; and R.sup.4 represents hydrogen, azido, pyridinium, alkoxy, acetoxy, carbamoyloxy, 5-(3-methylisoxazolyl)carbonylthio, alkoxythiocarbonylthio, 4- methyl-1- piperazinothiocarbonylthio; or oxazolylthio, thiazolylthio, imidazolylthio, pyrimidinylthio, oxadiazolylthio, thiadiazolylthio, triazolylthio, pyridine-1-oxide-2-ylthio or tetrazolylthio which may be substituted by alkyl; or 3-(2,6-dimethyl-5-oxo-2,5-dihydro-1,2,4-triazinyl)thio with the proviso that when R.sup.4 is pyridinium there is present a pharmaceutically acceptable counter-ion.
- 3. An antibacterial compound of claim 1, of the formula, ##STR603##
- 4. An antibacterial compound of claim 1, of the formula, ##STR604##
- 5. An antibacterial compound of claim 1, of the formula, ##STR605##
- 6. An antibacterial compound of claim 1, of the formula, ##STR606##
- 7. An antibacterial compound of claim 1, of the formula, ##STR607##
- 8. An antibacterial compound of claim 7, wherein R.sup.5 is phenyl, p-hydroxyphenyl, cycloalkadienyl or thienyl; A is a hydrogen, alkyl, alkenyl, aryl or aralkyl which may be substituted by halogen or hydroxy; each pair of R.sup.2 and R.sup.3 are linked to the same carbon atom, and each R.sup.2 and R.sup.3 of 2 pairs of R.sup.2 and R.sup.3 , which may be the same or different, represent individually hydrogen or alkyl; R.sup.1 represents a hydrogen atom, a pharmaceutically acceptable cation capable of forming a non-toxic salt or an ester-forming group capable of being easily removed by enzymes in a living body; R.sup.4 represents acetoxy, carbamoyloxy, 2-(5-methyl-1,3,4-thiadiazolyl)thio, 2-(1,3,4-thiadiazolyl)-thio, 2-(1-methyl-1,3,4-triazolyl)thio, 5-(1-methyl-1,2,3,4-tetrazolyl)thio 5-(1,2,3,4-tetrazolyl)thio.
- 9. An antibacterial compound of claim 7, wherein R.sup.5 represents phenyl or p-hydroxyphenyl; each pair of R.sup.2 and R.sup.3 are linked to the same carbon atom and each R.sup.2 and R.sup.3 of 2 pairs of R.sup.2 and R.sup.3, which may be the same or different, represent individually hydrogen or methyl; A represents methyl or ethyl; R.sup.1 represents a hydrogen atom, a pharmaceutically acceptable cation capable of forming a non-toxic salt or an ester-forming group capable of being easily removed by enzymes in a living body; and R.sup.4 represents acetoxy, 2-(5-methyl-1,3,4-thiadizolyl)thio, 2-(1,3,4-thiadiazolyl)thio, 2-(1-methyl-1,3,4-triazolyl)thio, 5-(1-methyl-1,2,3,4-tetrazolyl)thio or 5-(1,2,3,4-tetrazolyl)thio.
- 10. An antibacterial compound of claim 1, wherein R.sup.1 is selected from the group consisting of ester-forming groups capable of being removed by catalytic reduction, chemical reduction or hydrolysis under mild conditions and ester-forming groups capable of being easily removed by enzymes in a living body.
- 11. An antibacterial compound of claim 1, wherein R.sup.1 is a pharmaceutically acceptable cation capable of forming a non-toxic salt.
- 12. An antibacterial compound of claim 1, wherein R.sup.1 is a hydrogen atom.
- 13. A compound selected from the group consisting of
- 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinocarbonyl-amino)phenylacetamido]-3-methyl-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-ethyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-methyl-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-n-propyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-methyl-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-n-butyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-methyl-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-n-pentyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-methyl-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-n-hexyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-methyl-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-n-heptyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-methyl-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-n-octyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-methyl-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-acetoxymethyl-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-ethyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-acetoxymethyl-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-n-propyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-acetoxymethyl-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-iso-propyl-2,3-dioxo-1-piperazinohiocarbonylamino)phenylacetamido]-3-acetoxymethyl-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinothiocarbonylamino)phenylacetamido]-3-acetoxymethyl-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-ethyl-2,3-dioxo-1-piperazinothiocarbonylamino)phenylacetamido]-3-acetoxymethyl-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(5-methyl-1,3,4-thiadiazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-ethyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(5-methyl-1,3,4-thiadiazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-n-propyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(5-methyl-1,3,4-thiadiazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-n-butyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(5-methyl-1,3,4-thiadiazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-phenyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(5-methyl-1,3,4-thiadiazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[5-(1-methyl-1,2,3,4-tetrazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-ethyl-6-methyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[5-(1-methyl-1,2,3,4-tetrazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4,6-dimethyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[5-(1-methyl-1,2,3,4-tetrazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-phenyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[5-(1-methyl-1,2,3,4-tetrazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(1,3,4-thiadiazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-ethyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(1,3,4-thiadiazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(1-methyl-1,3,4-triazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-ethyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(1-methyl-1,3,4-triazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-phenyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(1-methyl-1,3,4-triazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinocarbonylamino)propionamido]-3-acetoxymethyl-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinocarbonylamino)-p-hydroxyphenylacetamido]-3-[5-(1-methyl-1,2,3,4-tetrazolyl)thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-azidomethyl-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-ethyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[5-(1-methyl-1,2,3,4-tetrazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[5-(1-methyl-1,2,3,4-tetrazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(1,3,4-triazolyl ) thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[5-(1,2,3,4-tetrazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-ethyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[5-(1,2,3,4-tetrazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(5-methyl-1,3,4-oxadiazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[3-(2,6-dimethyl-5-oxo-2,5-dihydro-1,2,4-triazinyl) thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-ethyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(4-methyloxazolyl) thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(4-methylthiazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-ethyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(pyridyl-1-oxide) thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-(2-thiazolinylthiomethyl)-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(1-methylimidazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-(2-pyrimidinylthiomethyl)-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-ethyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[3-(6-methylpyridazinyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[1-(4-methylpiperazino)-thiocarbonylthiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[5-(3-methylisoxazolyl)-carbonylthiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-ethoxythiocarbonylthiomethyl-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-ethyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-pyridinomethyl-.DELTA..sup.3 -cephem-4-carboxylic acid betaine, and
- 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-pyridinomethyl-.DELTA..sup.3 -cephem-4-carboxylic acid betaine.
- 14. A compound selected from the group consisting of
- 7-[D(-)-.alpha.-(4-ethoxycarbonyl-2-oxo-1-piperazinocarbonylamino)phenylacetamido]-3-methyl-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-n-hexyl-3-oxo-1-piperazinocarbonylamino)phenylacetamido]-3-methyl-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-acetyl-2-oxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(5-methyl-1,3,4-thiadiazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-methanesulfonyl-2-oxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(5-methyl-1,3,4-thiadiazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-methyl-2-oxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(5-methyl-1,3,4-thiadiazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-ethyl-2-oxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(5-methyl-1,3,4-thiadiazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-acetylaminocarbonyl-2-oxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(5-methyl-1,3,4-thiadiazolyl) thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-methyl-3-oxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(5-methyl-1,3,4-thiadiazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-ethyl-3-oxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(5-methyl-1,3,4-thiadiazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-acetyl-2-oxo-1-piperazinocarbonylamino)phenylacetamido]-3-[5-(1-methyl-1,2,3,4-tetrazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-methanesulfonyl-2-oxo-1-piperazinocarbonylamino)phenylacetamido]-3-[5-(1-methyl-1,2,3,4-tetrazolyl)thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-methyl-2-oxo-1-piperazinocarbonylamino)phenylacetamido]-3-[5-(1-methyl-1,2,3,4-tetrazolyl)thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-ethyl-2-oxo-1-piperazinocarbonylamino)phenylacetamido]-3-[5-(1-methyl-1,2,3,4-tetrazolyl) thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-acetylaminocarbonyl-2-oxo-1-piperazinocarbonylamino)phenylacetamido]-3-[(5-(1-methyl-1,2,3,4-tetrazolyl)thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid,
- 7-[D(-)-.alpha.-(4-methyl-3-oxo-1piperazinocarbonylamino)phenylacetamido]-3-[5-(1-methyl-1,2,3,4-tetrazolyl)thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid and
- 7-[D(-)-.alpha.-(4-ethyl-3-oxo-1-piperazinocarbonylamino)phenylacetamido]-3-[5-(1-methyl-1,2,3,4-tetrazolyl)thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid.
- 15. The compound of claim 7, which is 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(5-methyl-1,3,4-thiadiazolyl)thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid of the formula, ##STR608## or a non-toxic salt thereof.
- 16. The compound of claim 7 which is 7-[D(-)-.alpha.-(4-ethyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(5-methyl-1,3,4-thiadiazolyl)thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid of the formula, ##STR609## or a non-toxic salt thereof.
- 17. The compound of claim 7 which is 7-[D(-)-.alpha.-(4-methyl-2,3dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[5-(1-methyl-1,2,3,4-tetrazolyl)thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid of the formula, ##STR610## or a non-toxic salt thereof.
- 18. The compound of claim 7, which is 7-[D(-)-.alpha.-(4-ethyl-6-methyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[5-(1-methyl-1,2,3,4-tetrazolyl)thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid of the formula, ##STR611## or a non-toxic salt thereof.
- 19. The compound of claim 7, which is 7-[D(-)-.alpha.-(4,6-dimethyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[5-(1-methyl-1,2,3,4-tetrazolyl)thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid of the formula, ##STR612## or a non-toxic salt thereof.
- 20. The compound of claim 7, which is 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(1,3,4-thiadiazolyl)thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid of the formula, ##STR613## or a non-toxic salt thereof.
- 21. The compound of claim 7, which is 7-[D(-)-.alpha.-(4-ethyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(1,3,4-thiadiazolyl)thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid of the formula, ##STR614## or a non-toxic salt thereof.
- 22. The compound of claim 7, which is 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(1-methyl-1,3,4-triazolyl)thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid of the formula, ##STR615## or a non-toxic salt thereof.
- 23. The compound of claim 7, which is 7-[D(-)-.alpha.-(4-ethyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(1-methyl-1,3,4-triazolyl)thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid of the formula, ##STR616## or a non-toxic salt thereof.
- 24. The compound of claim 7, which is 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinocarbonylamino)-p-hydroxyphenylacetamido]-3-[5-(1-methyl-1,2,3,4-tetrazolyl)thiomethyl)-.DELTA..sup.3 -cephem-4-carboxylic acid of the formula, ##STR617## or a non-toxic salt thereof.
- 25. The compound of claim 7, which is 7-[D(-)-.alpha.-(4-ethyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[5-(1-methyl-1,2,3,4-tetrazolyl)thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid of the formula. ##STR618## on a non-toxic salt thereof.
- 26. The compound of claim 7, which is 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[2-(1,3,4-triazolyl)thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid of the formula, ##STR619## or a non-toxic salt thereof.
- 27. The compound of claim 7, which is 7-[D(-)-.alpha.-(4-methyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[5-(1,2,3,4-tetrazolyl)thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid of the formula, ##STR620## or a non-toxic salt thereof.
- 28. The compound of claim 7, which is 7-[D(-)-.alpha.-(4-ethyl-2,3-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[5-(1,2,3,4-tetrazolyl)thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid of the formula, ##STR621## or a non-toxic salt thereof.
- 29. The compound of claim 7, which is 7-[D(-)-.alpha.-(4-ethyl-2,3-dioxo-1-piperazinocarbonylamino)-p-hydroxyphenylacetamido]-3-[5-(1-methyl-1,2,3,4-tetrazolyl)thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid of the formula, ##STR622## or a non-toxic salt thereof.
- 30. The compound of claim 7, which is 7-[D(-)-.alpha.-(3,5-dioxo-1-piperazinocarbonylamino)-phenylacetamido]-3-[2-(5-methyl-1,3,4-thiadiazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid, 7-[D(-)-.alpha.-(4-acetyl-2,5-dioxo-1-piperazinocarbonyl-amino)phenylacetamido]-3-[2-(5-methyl-1,3,4-thiadiazolyl)thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid, 7-[D(-)-.alpha.-(3,5-dioxo-1-piperazinocarbonylamino)-phenylacetamido]-3-[5-(1-methyl-1,2,3,4-tetrazolyl)-thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid, and 7-[D(-)-.alpha.-(4-acetyl-2,5-dioxo-1-piperazinocarbonylamino)phenylacetamido]-3-[5-(5-(1-methyl-1,2,3,4-tetrazolyl)thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid.
- 31. A pharmaceutical composition comprising an antibacterially effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
- 32. A method of combatting bacteria in mammals which comprises administering to said mammal an antibacterially effective amount of a compound of claim 1.
- 33. A compound of the formula (I), ##STR623## wherein R is a group represented by the formula ##STR624## each of said moieties A, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 is a conventional cephalosporin substituent selected from the radicals or atoms which each of said moieties represents as set forth subsequently,
- wherein
- R.sup.5 represents methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentyl, cyclohexenyl, cyclopentadienyl, cyclohexadienyl, phenyl, naphthyl, benzyl, phenethyl, phenoxy, naphthoxy, methylthiomethyl, ethylthiomethyl, methylthioethyl, ethylthioethyl, furyl, thienyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, imidazolyl, pyrazolyl, pyridyl, pyrazyl, pyrimidyl, pyridazyl, quinolyl, isoquinolyl, quinazolyl, indolyl, indazolyl, 1,3,4-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-thiadiazolyl, or 1,2,4-thiadiazolyl; each group represented by said R.sup.5 may be substituted by halogen, hydroxy or nitro; R.sup.6 represents a hydrogen atom; and R.sup.5 and R.sup.6 together with a common carbon atom may form a cyclohexyl, cycloheptyl or cyclopentenyl, cyclohexenyl, cyclopentadienyl or cyclohexadienyl ring,
- R.sup.1 represents a hydrogen atom, a blocking group of a conventional cephalosporin or a pharmaceutically acceptable salt-forming cation of a conventional cephalosporin;
- n represents 1 or 2; each of the n X's, which may be identical or different from one another, represents individually an oxygen or sulfur atom, and the n X's are attached in any combination to the 2-, 3-, or 5-position of the piperazine ring;
- m represents 4-n; each pair of R.sup.2 and R.sup.3 are linked to the same carbon atom, and each R.sup.2 and R.sup.3 of m pairs of R.sup.2 and R.sup.3, which may be the same or different, represent individually, a hydrogen atom, a halogen atom, a carboxyl group, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, naphthyl, acetyl, propionyl, butyryl, benzoyl, benzyl, phenethyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, acetyloxymethyl, propionyloxymethyl, pivaloyloxymethyl, benzoyloxymethyl, methoxy, ethoxy, propoxy, butoxy, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, cyclopentyloxycarbonyl, cyclohexyloxycarbonyl, cycloheptyloxycarbonyl, benzyloxycarbonyl, phenethoxycarbonyl, phenoxycarbonyl, naphthoxycarbonyl, amino, N-methylamino, N-ethylamino, N-propylamino, N-butylamino, N,N-dimethylamino, N,N-diethylamino, N,N-dibutylamino, N-acetylamino, N-propionylamino, N-butyrylamino, N-benzoylamino, pyrrolidino, piperidino, morpholino, carbamoyl, N-methylaminocarbonyl, N-ethylaminocarbonyl, N,N-dimethylaminocarbonyl, N,N-diethylaminocarbonyl, and any pair of R.sup.2 and R.sup.3 together with a common carbon atom may form a cyclopentyl, cyclohexyl or cycloheptyl group, and each of the groups mentioned above for said R.sup.2 and R.sup.3 may be substituted by halogen or nitro;
- A represents hydrogen, hydroxyl, nitro, cyano, methyl, ethyl, propyl, isopropyl, butyl, pentyl, hexyl, heptyl, octyl, dodecyl, vinyl, propenyl, butenyl, propargyl, 1,3-butadienyl, 1,3-pentadienyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, cyclohexenyl, cyclopentadienyl, cyclohexadienyl, phenyl, naphthyl, formyl, acetyl, propionyl, isovaleryl, caproyl, enanthoyl, capryloyl, palmitoyl, stearoyl, acryloyl, cyclohexanecarbonyl, benzoyl, phenylglycyl, furoyl, thenoyl, benzyl, phenethyl, acetyloxyethyl, pivaloyloxymethyl, benzoyloxymethyl, methoxy, ethoxy, propoxy, butoxy, cyclopentyloxy, cyclohexyloxy, cycloheptyloxy, phenoxy, naphthoxy, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, cyclopentyloxycarbonyl, cyclohexyloxycarbonyl, cycloheptyloxycarbonyl, phenoxycarbonyl, (1- or 2-) naphthoxycarbonyl, benzyloxycarbonyl, phenethoxycarbonyl, methanesulfonyl, ethanesulfonyl, propanesulfonyl, butanesulfonyl, cyclopentanesulfonyl, cyclohexanesulfonyl, benzenesulfonyl, (1- or 2-)naphthalenesulfonyl, carbamoyl, N-methylaminocarbonyl, N-ethylaminocarbonyl, N-propylaminocarbonyl, N-butylaminocarbonyl, N-phenylaminocarbonyl, N,N-dimethylaminocarbonyl, N,N-diethylaminocarbonyl, pyrrolidinocarbonyl, piperidinocarbonyl, morpholinocarbonyl, thiocarbomoyl, N-methylaminothiocarbonyl, N-ethylaminothiocarbonyl, N-propylaminothiocarbonyl, N-phenylaminothiocarbonyl, N,N-dimethylaminothiocarbonyl, N,N-diethylaminothiocarbonyl, pyrrolidinothiocarbonyl, piperidinothiocarbonyl, morpholinothiocarbonyl, N-acetylcarbamoyl, N-propionylcarbomoyl, N-butyrylcarbamoyl, N-benzoylcarbamoyl, N-furoylcarbamoyl, N-thenoylcarbamoyl, N-acetylthiocarbamoyl, N-propionylthiocarbamoyl, N-butyrylthiocarbamoyl, N-benzoylthiocarbamoyl, N-naphthoylthiocarbamoyl, N-furoylthiocarbamoyl, N-thenoylthiocarbamoyl, methanesulfonylaminocarbonyl, ethanesulfonylaminocarbonyl, butanesulfonylaminocarbonyl, benzenesulfonylaminocarbonyl, (1- or 2-)naphthalenesulfonylaminocarbonyl, methanesulfonylaminothiocarbonyl, ethanesulfonylaminothiocarbonyl, butanesulfonylaminothiocarbonyl, benzenesulfonylaminothiocarbonyl, naphthalenesulfonylaminothiocarbonyl, sulfamoyl, N-methylsulfamoyl, N-ethylsulfamoyl, N-propylsulfamoyl, N-butylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N,N-dipropylsulfamoyl, N,N-dibutylsulfamoyl, N-phenylsulfamoyl, N-benzylsulfamoyl, N-cyclopentylsulfamoyl, N-cyclohexylsulfamoyl, methoxycarbonylthiomethyl, ethoxycarbonylthiomethyl, propoxycarbonylthiomethyl, butoxycarbonylthiomethyl, methoxycarbonylthioethyl, methoxythiocarbonylthiomethyl, ethoxythiocarbonylthiomethyl, propoxythiocarbonylthiomethyl, butoxythiocarbonlythiomethyl, methoxythiocarbonylthioethyl, amino, N-methylamino, N-ethylamino, N-propylamino, N-butylamino, N,N-dimethylamino, N,N-diethylamino, N,N-dibutylamino, N-acetylamino, N-propionylamino, N-butyrylamino, N-benzoylamino, pyrrolidino, piperidino, morpholino, thiazolyl, pyridyl, pyridazyl, pyrazyl, thiadiazolyl, triazolyl, tetrazolyl, quinolyl, any of which may be substituted by halogen, hydroxyl, nitro cyano or carboxyl groups;
- Y represents on oxygen or sulfur atom;
- R.sup.4 represents cyano, azido, pyridinium, quinolinium, isoquinolinium or pyrimidinium, methoxy, ethoxy, propoxy, phenoxy, naphthoxy, phenethoxy, acetyloxy, propionyloxy, butyryloxy, benzoyloxy, naphthoyloxy, cyclopentanecarbonyloxy, cyclohexanecarbonyloxy, furoyloxy, thenoyloxy, carbomoyloxy, N-methylaminocarbonyloxy, N,N-dimethylaminocarbonyloxy, N-acetylaminocarbonyloxy, phenylaminocarbonyloxy, benzylaminocarbonyloxy, cyclohexylaminocarbonyloxy, guanidino, N-methylguanidino, amino, N-methylamino, N-ethylamino, N-propylamino, N-butylamino, N-cyclohexylamino, N-phenylamino, N,N-dimethylamino, N,N-diethylamino, N,N-dibutylamino, pyrrolidino, piperidino, morpholino, methylthio, ethylthio, propylthio, phenylthio, (1- or 2-)-naphthylthio, benzylthio, phenethylthio, acetylthio, propionylthio, butyrylthio, benzoylthio, (1- or 2-)naphthoylthio, cyclopentanecarbonylthio, cyclohexanecarbonylthio, furoylthio, thenoylthio, isothiazolecarbonylthio, isoxazolecarbonylthio, thiadiazolecarbonylthio, thriazolecarbonylthio, thiocarbamoylthio, N-methylthiocarbamoylthio N,N-diethylthiocarbamoylthio, 1-piperidino-thiocarbonylthio, 1-morpholinothiocarbonylthio, 4-methyl-1-piperazinothiocarbonylthio, methoxythiocarbonylthio, ethoxythiocarbonylthio, propoxythiocarbonylthio, butoxythiocarbonylthio, phenoxythiocarbonylthio, cyclohexyloxythiocarbonylthio, amidinothio, N-methylamidinothio, N,N'-dimethylamidinothio, oxazolylthio, thiazolylthio, isoxazolylthio, isothiazolylthio, imidazolylthio, pyrazolylthio, pyridylthio, pyrazinylthio, pyrimidinylthio, pyridazinylthio, quinolylthio, isoquinolylthio, quinazolylthio, indolylthio, indazolylthio, oxadiazolylthio, thiadiazolylthio, triazolylthio, tetrazolylthio, triazinylthio, benzimidazolylthio, benzoxazolylthio, benzothiazolylthio, triazolopyridylthio, purinylthio, pyridine-1-oxide-2-ylthio or pyridazine-1-oxide-6-ylthio, each of which may be substituted by halogen, C.sub.1-4 alkyl, nitro cyano, carboxyl or carbamoyl, thiazolinylthio, or 3-(2,6dimethyl-5-oxo-2,5-dihyro 1,2,4-triazinyl)thio, with the proviso that when R.sup.4 is pyridinium, quinolinium, isoquinolinium, or pyrimidinium there is present a pharmaceutically acceptable counter-ion.
- 34. A compound of the formula (I), ##STR625## wherein R is a group represented by the formula ##STR626## each of said moieties A, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 is a conventional cephalosporin substitutent selected from the radicals or atoms which each of said moieties represents as set forth subsequently,
- wherein
- R.sup.5 represents methyl, ethyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, cyclohexenyl, cyclopentadienyl, cyclohexadienyl, phenyl, naphthyl, benzyl, phenoxy, naphthoxy, furyl, thienyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, imidazolyl, pyrazolyl, pyridyl, pyrazyl, pyrimidyl, pyridazyl, quinolyl, isoquinolyl, quinazolyl, indolyl, indazolyl, 1,3,4-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-thiadiazolyl or 1,2,4-thiadiazolyl; each group represented by said R.sup.5 may be substituted by halogen, hydroxy or nitro; R.sup.6 represents a hydrogen atom; and R.sup.5 and R.sup.6 together with a common carbon atom may form a cyclohexyl, cycloheptyl or cyclopentyl, cyclohexenyl, cyclopentadienyl or cyclohexadienyl ring;
- R.sup.1 represents a hydrogen atom, a blocking group of a conventional cephalosporin or a pharmaceutically acceptable salt-forming cation of a conventional cephalosporin;
- n represents 1 or 2; each of the X's, which may be identical or different from one another, represents individually an oxygen or sulfur atom, and the nX's are attached in any combination to the 2-, 3- or 5-position of the piperazine ring;
- m represents 4-n; each pair of R.sup.2 and R.sup.3 are linked to the same carboon atom, and each R.sup.2 and R.sup.3 of m pairs of R.sup.2 and R.sup.3, which may be the same or different, represent individually a hydrogen atom, a halogen atom, a carboxyl group, methyl, ethyl, propyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, acetyl, benzoyl, benzyl, acetyloxymethyl, pivaloyloxymethyl, methoxy, ethoxy, propoxy, methoxycarbonyl, ethoxycarbonyl, cyclohexyloxycarbonyl, benzyloxycarbonyl, phenoxycarbonyl, amino, N-methylamino, N-ethylamino, N,N-dimethylamino, N-acetylamino, carbamoyl, N-methylaminocarbonyl, N,N-dimethylaminocarbonyl, and any pair of R.sup.2 and R.sup.3 together with a common carbon atom may form a cyclopentyl or cyclohexyl group, and each of the groups mentioned above for said R.sup.2 and R.sup.3 may be substituted by halogen;
- A represents hydrogen, hydroxyl, nitro, cyano, methyl, ethyl, propyl, vinyl, propenyl, propargyl, 1,3-pentadienyl, cyclopentyl, cyclohexyl, cyclopentenyl, cyclohexenyl, cyclopentadienyl, cyclohexadienyl, phenyl, naphthyl, formyl, acetyl, propionyl, benzoyl, furoyl, thenoyl, benzyl, pivaloyloxymethyl, methoxy, ethoxy cyclopentyloxy, cyclohexyloxy, phenoxy, naphthoxy, methoxycarbonyl, ethoxycarbonyl, cyclopentyloxycarbonyl, cyclohexyloxycarbonyl, phenoxycarbonyl, benzyloxycarbonyl, methanesulfonyl, ethanesulfonyl, cyclohexanesulfonyl, benzenesulfonyl, carbamoly, N-methylaminocarbonyl, N-phenylaminocarbonyl, N,N-dimethylaminocarbonyl, pyrrolidinocarbonyl, piperidinocarbonyl, thiocarbamoyl, N-methylaminothiocarbonyl, N-phenylaminothiocarbonyl, N,N-dimethylaminothiocarbonyl, pyrrolidinothiocarbonyl, piperidinothiocarbonyl, N-acetylcarbamoyl, N-acetylthiocarbamoyl, methanesulfonylaminocarbonyl, methanesulfonylaminothiocarbonyl, sulfamoyl, N-methylsulfamoyl, N-ethylsulfamoyl, N,N-dimethylsulfamoyl, N-phenylsulfamoyl, N-cyclohexylsulfamoyl, amino, N-methylamino, N-ethylamino, N,N-dimethylamino, N-acetylamino, thiazolyl, pyridyl, pyridazyl, pyrazyl, any of which may be substituted by halogen, nitro, cyano or carboxyl groups;
- Y represents an oxygen or sulfur atom;
- R.sup.4 represents hydrogen, halogen, hydroxy, cyano, azido, pyridinium, quinolinium, isoquinolinium or pyrimidinium, methoxy, ethoxy, propoxy, phenoxy, naphthoxy, benzyloxy, acetyloxy, propionyloxy, butyryloxy, benzoyloxy, naphthoyloxy, cyclopentanecarbonyloxy, thenoyloxy, carbomoyloxy, N-methylaminocarbonyloxy, N,N-dimethylaminocarbonyloxy, N-acetylaminocarbonyloxy, phenylaminocarbonyloxy, benzylaminocarbonyloxy, cyclohexylaminocarbonyloxy, methylthio, ethylthio, propylthio, phenylthio, (1- or 2-)naphthylthio, benzylthio, acetylthio, propionylthio, butyrylthio, benzoylthio, (1- or 2-)naphthoylthio, cyclopentanecarbonylthio, thenoylthio, thiocarbamoylthio, N-methylthiocarbamoylthio, N,N-diethylthiocarbamoylthio, 1-piperidinothiocarbonylthio, 1-morpholinothiocarbonylthio, 4-methyl-1-piperazinothiocarbonylthio, methoxythiocarbonylthio, ethoxythiocarbonylthio, phenoxythiocarbonylthio, cyclohexyloxythiocarbonylthio, oxazolylthio, thiazolylthio, isoxazolylthio, isothiazolylthio, imidazolylthio, pyrazolylthio, pyridylthio, pyrazinylthio, pyrimidinylthio, pyridazinylthio, quinolythio, isoquinolylthio, quinazolylthio, indolylthio, indazolylthio, oxadiazolylthio, thiadiazolylthio, triazolylthio, tetrazolylthio, triazinylthio, benzimidazolylthio, benzoxazolylthio, benzothiazolylthio, triazolopyridylthio, purinylthio, each of which may be substituted by halogen, C.sub.1-4 alkyl, nitro, cyano, carboxyl or carbamoyls, thiazolinylthio, or 3-(2,6-dimethyl-5-oxo-2,5dihydro-1,2,4-triazinyl)thio, with the proviso that when R.sup.4 is pyridinium, quinolinium, isoquinolinium, or pyrimidinium there is present a pharamceutically acceptable counter-ion.
- 35. A compound of claim 34, wherein R.sup.5 represents methyl, ethyl, cyclopentadienyl, cyclohexadienyl, phenyl or 2-thienyl, each of which may be substituted by halogen, hydroxy or nitro; R.sup.6 represents a hydrogen atom; each pair of R.sup.2 and R.sup.3 are linked to the same carbon atom, and each R.sup.2 and R.sup.3 of m pairs of R.sup.2 and R.sup.3, which may be the same or different, represent individually a hydrogen atom, methyl, ethyl, propyl, or phenyl; A represents hydrogen, methyl, ethyl, propyl, vinyl, propenyl, benzyl or phenyl, any of which may be optionally substituted by a halogen atom; R.sup.4 represents acetoxy, carbamoyloxy or (1-methyl-1,2,3,4-tetrazolyl)thio groups; and R.sup.1 is a hydrogen atom, a conventional cephalosporin cation capable of forming a pharmaceutically acceptable non-toxic salt or a conventional cephalosporin ester forming group capable of being easily removed by enzymes in a living body.
- 36. A compound of claim 34, wherein R.sup.5 represents phenyl or 4-hydroxyphenyl; R.sup.6 represents hydrogen; each pair of R.sup.2 and R.sup.3 are linked to the same carbon atom, and each R.sup.2 and R.sup.3 of m pairs of R.sup.2 and R.sup.3, which may be the same or different, are individually a hydrogen atom or methyl; A represents methyl or ethyl; R.sup.4 represents acetoxy or (1-methoxy-1,2,3,4-tetrazolyl)thio groups; and R.sup.1 is a hydrogen atom, or a conventional cephlosporin cation capable of forming a pharamceutically acceptable non-toxic salt.
- 37. The compound of claim 36, which is 7-D(-)-.alpha.-(4-ethyl-2,3-dioxo-1-piperazinocarbonylamino)-p-hydroxyphenylacetamide]-3-[5-(1-methyl-1,2,3,4-tetrazolyl)thiomethyl]-.DELTA..sup.3 -cephem-4-carboxylic acid of the formula, ##STR627## or its sodium salt.
- 38. A D(-)-isomer of a compound of ##STR628## wherein Y is hydrogen, R.sup.1 is hydrogen or halogen, R.sup.2 is lower alkyl and R.sup.3 is hydrogen or lower alkyl,and pharmaceutically acceptable salts thereof.
- 39. A compound as claimed in claim 38, wherein the pharmaceutically acceptable salt is an alkali metal salt.
- 40. A compound as claimed in claim 38, wherein the pharmaceutically acceptable salt is the sodium or potassium salt.
- 41. A pharmaceutical composition having antibacterial activity which comprises an effective amount of a compound as claimed in claim 38 and a pharmaceutically acceptable carrier therefor.
- 42. A D(-)-isomer of a compound of the formula (I): ##STR629## wherein Y is hydrogen, R.sup.1 is hydrogen, R.sup.2 is lower alkyl and R.sup.3 is hydrogen or lower alkyl, and pharmaceutically acceptable salts thereof.
- 43. A compound as claimed in claim 42, wherein the pharmaceutically acceptable salt is an alkali metal salt.
- 44. A compound as claimed in claim 42, wherein the pharmaceutically acceptable salt is the sodium or potassium salt.
- 45. 7-[D(-)-.alpha.-(4-ethyl-2,3-dioxopiperazin-1-yl-carbonylamino)-p-hydroxyphenylacetamido]-3-(1,3,4-thiadiazol-2-yl-thiomethyl)-3-cephem-4-carboxylic acid as claimed in claim 42.
- 46. 7-[D(-)-.alpha.-(4-ethyl-2,3-dioxopiperazin-1-yl-carbonylamino)-p-hydroxyphenylacetamido]-3-(5-methyl-1,3,4-thiadiazol-2-yl-thiomethyl)-3-cephem-4-carboxylic acid as claimed in claim 42.
- 47. A pharmaceutical composition having antibacterial activity which comprises an effective amount of a compound as claimed in claim 42 and a pharmaceutically acceptable carrier therefor.
Priority Claims (7)
Number |
Date |
Country |
Kind |
54-50663 |
May 1974 |
JPX |
|
49-52254 |
May 1974 |
JPX |
|
49-60787 |
May 1974 |
JPX |
|
49-91996 |
Aug 1974 |
JPX |
|
49-109954 |
Sep 1974 |
JPX |
|
49-142499 |
Dec 1974 |
JPX |
|
50-37207 |
Mar 1975 |
JPX |
|
CROSS-REFERENCES TO RELATED APPLICATIONS
This application is a division of application Ser. No. 654,060 filed Jan. 30, 1976, now U.S. Pat. No. 4,112,090, which is a continuation-in-part of application Ser. No. 571,479 filed Apr. 24, 1975, now U.S. Pat. No. 4,087,424.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
4103008 |
Toshiyasu et al. |
Jul 1978 |
|
Divisions (1)
|
Number |
Date |
Country |
Parent |
654060 |
Jan 1976 |
|
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
571479 |
Apr 1975 |
|