CA1316171C - Cephalosporin derivatives - Google Patents
Cephalosporin derivativesInfo
- Publication number
- CA1316171C CA1316171C CA000280699A CA280699A CA1316171C CA 1316171 C CA1316171 C CA 1316171C CA 000280699 A CA000280699 A CA 000280699A CA 280699 A CA280699 A CA 280699A CA 1316171 C CA1316171 C CA 1316171C
- Authority
- CA
- Canada
- Prior art keywords
- ester
- syn
- formula
- carboxylic acid
- salt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 229930186147 Cephalosporin Natural products 0.000 title claims abstract description 17
- 229940124587 cephalosporin Drugs 0.000 title claims abstract description 17
- 150000001780 cephalosporins Chemical class 0.000 title claims abstract description 17
- -1 carbamoyloxy Chemical group 0.000 claims abstract description 160
- 150000003839 salts Chemical class 0.000 claims abstract description 139
- 150000002148 esters Chemical class 0.000 claims abstract description 112
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 29
- 239000001257 hydrogen Substances 0.000 claims abstract description 29
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 11
- 125000001453 quaternary ammonium group Chemical group 0.000 claims abstract description 11
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims description 165
- 238000000034 method Methods 0.000 claims description 113
- 239000011734 sodium Substances 0.000 claims description 92
- 239000000203 mixture Substances 0.000 claims description 86
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 76
- 229910052708 sodium Inorganic materials 0.000 claims description 57
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 56
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 45
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 41
- 239000000460 chlorine Substances 0.000 claims description 40
- 239000002253 acid Substances 0.000 claims description 32
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 32
- 125000000217 alkyl group Chemical group 0.000 claims description 28
- 125000000623 heterocyclic group Chemical group 0.000 claims description 23
- 125000003545 alkoxy group Chemical group 0.000 claims description 21
- 230000008569 process Effects 0.000 claims description 19
- 125000001424 substituent group Chemical group 0.000 claims description 19
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 16
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 15
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 14
- 125000006239 protecting group Chemical group 0.000 claims description 14
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 13
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 13
- 229910052794 bromium Chemical group 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 9
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- 239000011591 potassium Substances 0.000 claims description 9
- 229910052700 potassium Inorganic materials 0.000 claims description 9
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 9
- 150000003573 thiols Chemical class 0.000 claims description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 7
- 150000002431 hydrogen Chemical class 0.000 claims description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 4
- 125000003277 amino group Chemical group 0.000 claims description 4
- 230000000845 anti-microbial effect Effects 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 3
- 239000004599 antimicrobial Substances 0.000 claims description 3
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 3
- 150000001768 cations Chemical group 0.000 claims description 3
- 125000001188 haloalkyl group Chemical group 0.000 claims description 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 125000004434 sulfur atom Chemical group 0.000 claims description 3
- 239000003981 vehicle Substances 0.000 claims description 3
- 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 claims description 2
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 claims description 2
- 125000004080 3-carboxypropanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C(O[H])=O 0.000 claims description 2
- 125000004633 N-oxo-pyridyl group Chemical group 0.000 claims description 2
- 125000002339 acetoacetyl group Chemical group O=C([*])C([H])([H])C(=O)C([H])([H])[H] 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-O hydron;quinoline Chemical compound [NH+]1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-O 0.000 claims description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 229910052698 phosphorus Inorganic materials 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 9
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 4
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims 2
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims 2
- 125000003282 alkyl amino group Chemical group 0.000 claims 2
- 238000010561 standard procedure Methods 0.000 claims 2
- RXZMDWJNCIUFAR-WCRCJTMVSA-N (6R)-3-(acetyloxymethyl)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound NC=1SC=C(N=1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)COC(C)=O)C(=O)O)C1=O)=NO RXZMDWJNCIUFAR-WCRCJTMVSA-N 0.000 claims 1
- XTGYRLHGQXKRQU-PLNQYNMKSA-N (6R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-3-(carbamoyloxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N=C1SC=C(N1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)COC(N)=O)C(=O)O)C1=O)=NO XTGYRLHGQXKRQU-PLNQYNMKSA-N 0.000 claims 1
- WMYKYUYFKKFXRX-LESKNEHBSA-N (6R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound NC=1SC=C(N=1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)CSC2=NN=NN2C)C(=O)O)C1=O)=NO WMYKYUYFKKFXRX-LESKNEHBSA-N 0.000 claims 1
- SCNOPTQROMQNHU-WCRCJTMVSA-N (6R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-3-[(3-methyl-1,2,4-thiadiazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N=C1SC=C(N1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)CSC2=NC(=NS2)C)C(=O)O)C1=O)=NO SCNOPTQROMQNHU-WCRCJTMVSA-N 0.000 claims 1
- AUYJNWSBDCLAFY-LNUXAPHWSA-N (6R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-3-[(4,5-dimethyl-1,2,4-triazol-3-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N=C1SC=C(N1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)CSC=2N(C(=NN=2)C)C)C(=O)O)C1=O)=NO AUYJNWSBDCLAFY-LNUXAPHWSA-N 0.000 claims 1
- KPBOAJBQSCOKHD-WCRCJTMVSA-N (6R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-3-[(4-methyl-1,2,4-triazol-3-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N=C1SC=C(N1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)CSC2=NN=CN2C)C(=O)O)C1=O)=NO KPBOAJBQSCOKHD-WCRCJTMVSA-N 0.000 claims 1
- QSNNGYKGPAOZKX-WCRCJTMVSA-N (6R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-3-[(5-methyl-1,3,4-oxadiazol-2-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N=C1SC=C(N1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)CSC2=NN=C(O2)C)C(=O)O)C1=O)=NO QSNNGYKGPAOZKX-WCRCJTMVSA-N 0.000 claims 1
- APVOWJJCTNSILR-WCRCJTMVSA-N (6R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-3-[[1-(2-hydroxyethyl)tetrazol-5-yl]sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N=C1SC=C(N1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)CSC2=NN=NN2CCO)C(=O)O)C1=O)=NO APVOWJJCTNSILR-WCRCJTMVSA-N 0.000 claims 1
- GBWAXAMERQBSMC-WCRCJTMVSA-N (6R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-3-[[5-(hydroxymethyl)-1,3,4-thiadiazol-2-yl]sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N=C1SC=C(N1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)CSC2=NN=C(S2)CO)C(=O)O)C1=O)=NO GBWAXAMERQBSMC-WCRCJTMVSA-N 0.000 claims 1
- SLYKFULQWCCURV-LNUXAPHWSA-N (6R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-3-[[5-(hydroxymethyl)-4-methyl-1,2,4-triazol-3-yl]sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N=C1SC=C(N1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)CSC=2N(C(=NN=2)CO)C)C(=O)O)C1=O)=NO SLYKFULQWCCURV-LNUXAPHWSA-N 0.000 claims 1
- LVAIYFOEIOXERM-LNUXAPHWSA-N (6R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-3-[[5-(methoxymethyl)-1,3,4-thiadiazol-2-yl]sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N=C1SC=C(N1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)CSC2=NN=C(S2)COC)C(=O)O)C1=O)=NO LVAIYFOEIOXERM-LNUXAPHWSA-N 0.000 claims 1
- FMPXXFJEIVCXCL-PLNQYNMKSA-N (6R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CC=1CS[C@H]2N(C=1C(=O)O)C(C2NC(C(=NO)C=1N=C(SC=1)N)=O)=O FMPXXFJEIVCXCL-PLNQYNMKSA-N 0.000 claims 1
- DRKMALUDOKILMZ-LESKNEHBSA-N (6R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-8-oxo-3-(1,3,4-thiadiazol-2-ylsulfanylmethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N=C1SC=C(N1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)CSC=2SC=NN=2)C(=O)O)C1=O)=NO DRKMALUDOKILMZ-LESKNEHBSA-N 0.000 claims 1
- OVBDWAMFZKFJPT-WCRCJTMVSA-N (6R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-8-oxo-3-(2H-triazol-4-ylsulfanylmethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N=C1SC=C(N1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)CSC=2N=NNC=2)C(=O)O)C1=O)=NO OVBDWAMFZKFJPT-WCRCJTMVSA-N 0.000 claims 1
- 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 claims 1
- 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 claims 1
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 claims 1
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 claims 1
- 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 claims 1
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims 1
- 125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 claims 1
- 125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 claims 1
- 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 claims 1
- LHGNZAPCNCSDTE-MNWKQKBLSA-N 1-ethoxycarbonyloxyethyl (6R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-3-(carbamoyloxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound N=C1SC=C(N1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)COC(N)=O)C(=O)OC(C)OC(=O)OCC)C1=O)=NO LHGNZAPCNCSDTE-MNWKQKBLSA-N 0.000 claims 1
- XOHZHMUQBFJTNH-UHFFFAOYSA-N 1-methyl-2h-tetrazole-5-thione Chemical compound CN1N=NN=C1S XOHZHMUQBFJTNH-UHFFFAOYSA-N 0.000 claims 1
- JSZZAMPHCQQBOE-JOPIAHFSSA-N 2,2-dimethylpropanoyloxymethyl (6R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-3-(carbamoyloxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound N=C1SC=C(N1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)COC(N)=O)C(=O)OCOC(C(C)(C)C)=O)C1=O)=NO JSZZAMPHCQQBOE-JOPIAHFSSA-N 0.000 claims 1
- VCCRCPDEMYOPOL-LRHAYUFXSA-N 2,2-dimethylpropanoyloxymethyl (6R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound N=C1SC=C(N1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)CSC2=NN=C(S2)C)C(=O)OCOC(C(C)(C)C)=O)C1=O)=NO VCCRCPDEMYOPOL-LRHAYUFXSA-N 0.000 claims 1
- UOTQEHLQKASWQO-UHFFFAOYSA-N 2-(5-sulfanylidene-2h-tetrazol-1-yl)acetic acid Chemical compound OC(=O)CN1N=NN=C1S UOTQEHLQKASWQO-UHFFFAOYSA-N 0.000 claims 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims 1
- 125000004848 alkoxyethyl group Chemical group 0.000 claims 1
- 125000004849 alkoxymethyl group Chemical group 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000002883 imidazolyl group Chemical group 0.000 claims 1
- 150000003951 lactams Chemical class 0.000 claims 1
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 claims 1
- 125000002098 pyridazinyl group Chemical group 0.000 claims 1
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 1
- DNQKIMKGKFFXBR-SXMPBOCKSA-M sodium (6R)-3-(acetyloxymethyl)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound N=C1SC=C(N1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)COC(C)=O)C(=O)[O-])C1=O)=NO.[Na+] DNQKIMKGKFFXBR-SXMPBOCKSA-M 0.000 claims 1
- 125000004149 thio group Chemical class *S* 0.000 abstract description 3
- 239000003242 anti bacterial agent Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 102
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 81
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 78
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 66
- CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical group C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 description 65
- 239000000243 solution Substances 0.000 description 63
- 238000004519 manufacturing process Methods 0.000 description 58
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 56
- 238000005481 NMR spectroscopy Methods 0.000 description 55
- 238000006243 chemical reaction Methods 0.000 description 50
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 42
- 239000000843 powder Substances 0.000 description 42
- 239000000047 product Substances 0.000 description 42
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 40
- 239000011541 reaction mixture Substances 0.000 description 39
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 34
- 239000002904 solvent Substances 0.000 description 33
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 28
- 238000001914 filtration Methods 0.000 description 27
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 26
- 229940073584 methylene chloride Drugs 0.000 description 25
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 24
- 238000000921 elemental analysis Methods 0.000 description 21
- 238000001816 cooling Methods 0.000 description 20
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 20
- 235000017557 sodium bicarbonate Nutrition 0.000 description 20
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 20
- 239000007864 aqueous solution Substances 0.000 description 19
- 125000004432 carbon atom Chemical group C* 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 238000011161 development Methods 0.000 description 18
- 239000011259 mixed solution Substances 0.000 description 17
- 229920001429 chelating resin Polymers 0.000 description 16
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 15
- 238000004440 column chromatography Methods 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 15
- 229920006395 saturated elastomer Polymers 0.000 description 15
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 15
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- 244000052769 pathogen Species 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940007042 proteus vulgaris Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- FBBHPHRBJLLIFM-UHFFFAOYSA-N pyridin-1-ium-1-carboxylate Chemical compound [O-]C(=O)[N+]1=CC=CC=C1 FBBHPHRBJLLIFM-UHFFFAOYSA-N 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-O pyridin-1-ium-3-carboxylic acid Chemical compound OC(=O)C1=CC=C[NH+]=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-O 0.000 description 1
- VFQXVTODMYMSMJ-UHFFFAOYSA-O pyridin-1-ium-4-carboxamide Chemical compound NC(=O)C1=CC=[NH+]C=C1 VFQXVTODMYMSMJ-UHFFFAOYSA-O 0.000 description 1
- TWBYWOBDOCUKOW-UHFFFAOYSA-O pyridin-1-ium-4-carboxylic acid Chemical compound OC(=O)C1=CC=[NH+]C=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-O 0.000 description 1
- PTWLOSARXIJRRJ-UHFFFAOYSA-N pyridin-1-ium-4-sulfonate Chemical compound OS(=O)(=O)C1=CC=NC=C1 PTWLOSARXIJRRJ-UHFFFAOYSA-N 0.000 description 1
- DFPAKSUCGFBDDF-UHFFFAOYSA-O pyridine-3-carbonylazanium Chemical compound NC(=O)C1=CC=C[NH+]=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-O 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 208000020029 respiratory tract infectious disease Diseases 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- ALNPIWZUHLVKSW-SXMPBOCKSA-M sodium (6R)-3-[[1-(2-amino-2-oxoethyl)tetrazol-5-yl]sulfanylmethyl]-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound N=C1SC=C(N1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)CSC2=NN=NN2CC(N)=O)C(=O)[O-])C1=O)=NO.[Na+] ALNPIWZUHLVKSW-SXMPBOCKSA-M 0.000 description 1
- OXWMKOWFJCLNBZ-QFBOXNNLSA-M sodium (6R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-8-oxo-3-(1,3,4-thiadiazol-2-ylsulfanylmethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound N=C1SC=C(N1)C(C(=O)NC1[C@@H]2N(C(=C(CS2)CSC=2SC=NN=2)C(=O)[O-])C1=O)=NO.[Na+] OXWMKOWFJCLNBZ-QFBOXNNLSA-M 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000005415 substituted alkoxy group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000004964 sulfoalkyl group Chemical group 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Inorganic materials O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 125000002769 thiazolinyl group Chemical group 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 125000005289 uranyl group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/24—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with hydrocarbon radicals, substituted by hetero atoms or hetero rings, attached in position 3
- C07D501/26—Methylene radicals, substituted by oxygen atoms; Lactones thereof with the 2-carboxyl group
- C07D501/34—Methylene radicals, substituted by oxygen atoms; Lactones thereof with the 2-carboxyl group with the 7-amino radical acylated by carboxylic acids containing hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/24—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with hydrocarbon radicals, substituted by hetero atoms or hetero rings, attached in position 3
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Cephalosporin Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP108101/76 | 1976-09-08 | ||
| JP51108101A JPS6011713B2 (ja) | 1976-09-08 | 1976-09-08 | セフアロスポリン誘導体およびその製造法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1316171C true CA1316171C (en) | 1993-04-13 |
Family
ID=14475887
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000280699A Expired - Fee Related CA1316171C (en) | 1976-09-08 | 1977-06-16 | Cephalosporin derivatives |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US4264595A (en, 2012) |
| JP (1) | JPS6011713B2 (en, 2012) |
| AT (1) | AT352277B (en, 2012) |
| AU (1) | AU508551B2 (en, 2012) |
| BE (1) | BE856045A (en, 2012) |
| CA (1) | CA1316171C (en, 2012) |
| CH (4) | CH629813A5 (en, 2012) |
| DE (3) | DE2727753A1 (en, 2012) |
| DK (2) | DK159783C (en, 2012) |
| ES (2) | ES460124A1 (en, 2012) |
| FI (1) | FI67384C (en, 2012) |
| FR (1) | FR2408612A1 (en, 2012) |
| GB (1) | GB1587941A (en, 2012) |
| GR (1) | GR63635B (en, 2012) |
| HU (1) | HU182053B (en, 2012) |
| MX (1) | MX5198E (en, 2012) |
| NL (1) | NL189354C (en, 2012) |
| NO (1) | NO772170L (en, 2012) |
| PH (2) | PH15144A (en, 2012) |
| PT (1) | PT66735B (en, 2012) |
| SE (1) | SE464581B (en, 2012) |
| ZA (1) | ZA773775B (en, 2012) |
Families Citing this family (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5760345B2 (en, 2012) * | 1974-12-19 | 1982-12-18 | Takeda Chemical Industries Ltd | |
| SE440655B (sv) | 1976-01-23 | 1985-08-12 | Roussel Uclaf | Sett att framstella nya oximderivat av 7-amino-tiazolyl-acetamido-cefalosporansyra |
| DE2760123C2 (de) * | 1976-01-23 | 1986-04-30 | Roussel-Uclaf, Paris | 7-Aminothiazolyl-syn-oxyiminoacetamidocephalosporansäuren, ihre Herstellung und sie enthaltende pharmazeutische Zusammensetzungen |
| US4963542A (en) * | 1976-09-08 | 1990-10-16 | Takeda Chemical Industries, Ltd. | Cephalosporin derivatives |
| PH17188A (en) * | 1977-03-14 | 1984-06-14 | Fujisawa Pharmaceutical Co | New cephem and cepham compounds and their pharmaceutical compositions and method of use |
| SE439312B (sv) * | 1977-03-25 | 1985-06-10 | Roussel Uclaf | Sett att framstella nya oximderivat av 3-acetoximetyl-7-aminotiazolylacetamido cefalosporansyra |
| DE2714880A1 (de) * | 1977-04-02 | 1978-10-26 | Hoechst Ag | Cephemderivate und verfahren zu ihrer herstellung |
| US5089490A (en) * | 1977-04-02 | 1992-02-18 | Hoechst Aktiengesellschaft | Cephem derivatives |
| FR2410655A1 (fr) | 1977-12-05 | 1979-06-29 | Roussel Uclaf | Nouvelles oximes derivees de l'acide 3-substitue 7-amino thiazolyl acetamido cephalosporanique, leur procede de preparation et leur application comme medicaments |
| FR2387235A1 (fr) * | 1978-01-23 | 1978-11-10 | Fujisawa Pharmaceutical Co | Procede de preparation de composes d'acide 3,7-disubstitue-3-cephem-4-carboxylique et nouveaux produits ainsi obtenus, ayant une forte activite antibacterienne |
| US4341775A (en) * | 1978-09-11 | 1982-07-27 | Fujisawa Pharmaceutical Co., Ltd. | Cephem compounds |
| EP0048504B1 (en) * | 1978-09-12 | 1988-08-17 | Fujisawa Pharmaceutical Co., Ltd. | Intermediate compounds for preparing cephem compounds; processes for their preparation and processes for preparing cephem compounds |
| US4379922A (en) * | 1978-09-12 | 1983-04-12 | Fujisawa Pharmaceutical Co., Ltd. | Cepham compounds |
| DE2945248A1 (de) * | 1978-11-13 | 1980-05-22 | Fujisawa Pharmaceutical Co | Cephem-verbindungen, verfahren zu ihrer herstellung und sie enthaltende antibakterielle pharmazeutische mittel |
| DK222180A (da) * | 1979-05-23 | 1980-11-24 | Rhone Poulenc Ind | Fremgangsmaade til fremstilling af 3-thiovinylcephalosporiner |
| FR2476087A1 (fr) * | 1980-02-18 | 1981-08-21 | Roussel Uclaf | Nouvelles oximes derivees de l'acide 3-alkyloxy ou 3-alkyl-thiomethyl 7-amino thiazolyl acetamido cephalosporanique, leur procede de preparation et leur application comme medicaments |
| JPS56125392A (en) * | 1980-03-06 | 1981-10-01 | Fujisawa Pharmaceut Co Ltd | Cepham and cephem compound and preparation thereof |
| IT1141286B (it) * | 1980-04-17 | 1986-10-01 | Dob Far Spa | Esteri delle desacetossi cefalosporine loro sali e procedimenti per il loro ottenimento |
| JPS5759894A (en) * | 1980-09-30 | 1982-04-10 | Sankyo Co Ltd | Cephalosporin for oral administration |
| DK379581A (da) * | 1980-10-06 | 1982-04-07 | Hoffmann La Roche | Fremgangsmaade til fremstilling af acylderivater |
| US4431642A (en) * | 1980-12-01 | 1984-02-14 | Fujisawa Pharmaceutical Co., Ltd. | Cephem compounds |
| EP0061234A3 (en) * | 1981-03-05 | 1983-11-16 | Beecham Group Plc | Cephalosporin derivatives, process for their preparation and pharmaceutical preparations containing them |
| US4336253A (en) * | 1981-03-11 | 1982-06-22 | Eli Lilly And Company | Cephalosporin antibiotics |
| DE3118732A1 (de) * | 1981-05-12 | 1982-12-02 | Hoechst Ag, 6000 Frankfurt | Cephalosporinderivate und verfahren zu ihrer herstellung |
| FR2508458A1 (fr) * | 1981-06-29 | 1982-12-31 | Sandoz Sa | Nouveaux derives de l'acide cephalosporanique, leur preparation et leur application comme medicaments |
| US4406898A (en) * | 1981-09-08 | 1983-09-27 | Eli Lilly And Company | Oxazole and oxadiazole cephalosporins |
| US4396620A (en) * | 1981-09-08 | 1983-08-02 | Eli Lilly And Company | Cephalosporin quinolinium betaines |
| US4396619A (en) * | 1981-09-08 | 1983-08-02 | Eli Lilly And Company | Cephalosporin betaines |
| US4576938A (en) * | 1981-12-08 | 1986-03-18 | Tanabe Seiyaku Co., Ltd. | Cephalosporin compound and process for preparing the same |
| GB8323034D0 (en) * | 1983-08-26 | 1983-09-28 | Fujisawo Pharmaceutical Co Ltd | 7-substituted-3-vinyl-3-cephem compounds |
| US4761409A (en) * | 1984-08-16 | 1988-08-02 | Sumitomo Pharmaceuticals Company, Limited | Cephem derivatives |
| DE3587997D1 (de) * | 1984-12-27 | 1995-04-06 | Banyu Pharma Co Ltd | Isoindolinderivate. |
| GB8519606D0 (en) * | 1985-08-05 | 1985-09-11 | Fujisawa Pharmaceutical Co | 3 7-d substituted-3-cephem compounds |
| NO862910L (no) * | 1985-08-05 | 1987-02-06 | Fujisawa Pharmaceutical Co | Fremgangsmaate for fremstilling av 3,7-disubstituerte-3-cefemforbindelser. |
| US4814328A (en) * | 1986-03-19 | 1989-03-21 | Banyu Pharmaceutical Co., Ltd. | Cephalosporin derivatives, and antibacterial agents |
| JPS6417892A (en) * | 1987-07-14 | 1989-01-20 | Totoku Electric | Iron coated composite material and production thereof |
| JPH01230547A (ja) * | 1988-01-14 | 1989-09-14 | Takeda Chem Ind Ltd | ３−オキソ酪酸第三ブチルの製造法及びその用途 |
| DE3804841A1 (de) * | 1988-02-17 | 1989-08-31 | Hoechst Ag | Cephalosporinderivate und verfahren zu ihrer herstellung |
| EP0333082A3 (en) * | 1988-03-15 | 1991-05-02 | Takeda Chemical Industries, Ltd. | Cephem compounds, their production and use |
| JPH0347187A (ja) * | 1989-04-12 | 1991-02-28 | Yamanouchi Pharmaceut Co Ltd | 新規なセファロスポリン誘導体 |
| DE3919259A1 (de) * | 1989-06-13 | 1990-12-20 | Hoechst Ag | Kristalline cephem-saeureadditionssalze und verfahren zu ihrer herstellung |
| CA2054126A1 (en) * | 1990-10-26 | 1992-04-27 | Michiyuki Sendai | Cephem compounds, their production and use |
| IL99898A (en) | 1990-11-09 | 1996-10-31 | Eisai Co Ltd | 7-Acyl-3-substituted carbamoyloxy cephem compounds their preparation and antibacterial compositions containing them |
| YU48484B (sh) * | 1991-05-24 | 1998-09-18 | Hoechst Aktiengesellschaft | Kristalne kiselinske adicione soli diastereomerno čistih 1-(2,2-dimetilpropioniloksi)-etilestara 3-cefem-4-karbonske kiseline |
| ES2215161T3 (es) * | 1991-09-07 | 2004-10-01 | Aventis Pharma Deutschland Gmbh | Diastereoisomero del ester 1-(isopropoxicarboniloxi)-etilico del acido 3-cefem-4-carboxilico y procedimiento para su preparacion. |
| TW212181B (en, 2012) * | 1992-02-14 | 1993-09-01 | Hoechst Ag | |
| DE59308295D1 (de) * | 1992-05-21 | 1998-04-30 | Hoechst Ag | Verfahren zur Spaltung von Cephalosporin Prodrugestern zu 7-Amino-3-methoxymethylceph-3-em-4-carbonsäure |
| WO2009049086A1 (en) | 2007-10-09 | 2009-04-16 | Larry Sutton | Broad spectrum beta-lactamase inhibitors |
| US8802387B2 (en) | 2008-04-30 | 2014-08-12 | Nanyang Technological University | Methods and compounds for detecting beta-lactamase activity |
| WO2010118361A1 (en) * | 2009-04-09 | 2010-10-14 | Sopharmia, Inc. | Beta lactamase inhibitors |
| EP2968352B1 (en) | 2013-03-12 | 2018-09-26 | Gladius Pharmaceuticals Corporation | Derivatized 3-styryl-cephalosporins |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4024134A (en) * | 1971-01-29 | 1977-05-17 | Glaxo Laboratories Limited | Syn isomers of cephalosporins having α-hydroximino- or α-acyloxyiminoacylamido groups at position-7 |
| US4093803A (en) * | 1971-05-14 | 1978-06-06 | Glaxo Laboratories Limited | 7β-[2-Etherified oximino-2-(thienyl-, furyl- or pyridylacetamido)] cephalosporins |
| US4033950A (en) * | 1971-05-14 | 1977-07-05 | Glaxo Laboratories Limited | 3-Hydroxymethyl-7β-(2-alkoxy-or benzyloxyimino-2-arylacetamido)ceph-3-em-4-carboxylic acids and salts thereof |
| US4091209A (en) * | 1971-05-14 | 1978-05-23 | Glaxo Laboratories Limited | 7β-[2-Etherified oximino-2-(phenyl or naphthylacetamido)]cephalosporins having a 2-haloalkylcarbamoyloxymethyl group at the 3-position |
| US4024137A (en) * | 1971-05-14 | 1977-05-17 | Glaxo Laboratories Limited | 7β-[2-Etherified oximino-2-(phenyl- or naphthylacetamido)] cephalosporins |
| JPS5119765A (en) * | 1974-08-09 | 1976-02-17 | Takeda Chemical Industries Ltd | Aminochiazoorujudotaino seizoho |
| DK154939C (da) | 1974-12-19 | 1989-06-12 | Takeda Chemical Industries Ltd | Analogifremgangsmaade til fremstilling af thiazolylacetamido-cephemforbindelser eller farmaceutisk acceptable salte eller estere deraf |
| FR2346014A1 (fr) * | 1976-01-23 | 1977-10-28 | Roussel Uclaf | Nouvelles oximes derivees de l'acide 7-amino thiazolyl acetamido cephalosporanique, leur procede de preparation et leur application comme medicaments |
| FR2361894A2 (fr) * | 1976-01-23 | 1978-03-17 | Roussel Uclaf | Nouvelles oximes derivees de l'acide 7-aminothiazolyl acetamido cephalosporanique, leur procede de preparation et leur application comme medicaments |
| DE2760123C2 (de) * | 1976-01-23 | 1986-04-30 | Roussel-Uclaf, Paris | 7-Aminothiazolyl-syn-oxyiminoacetamidocephalosporansäuren, ihre Herstellung und sie enthaltende pharmazeutische Zusammensetzungen |
| FR2383188A2 (fr) * | 1976-01-23 | 1978-10-06 | Roussel Uclaf | Nouvelles oximes derivees de l'acide 7-amino thiazolyl acetamido cephalosporanique, leur procede de preparation et leur application comme medicaments |
| FR2361893A2 (fr) * | 1976-01-23 | 1978-03-17 | Roussel Uclaf | Nouvelles oximes derivees de l'acide 7-amino thiazolyl acetamido cephalosporanique, leur procede de preparation et leur application comme medicaments |
-
1976
- 1976-09-08 JP JP51108101A patent/JPS6011713B2/ja not_active Expired
-
1977
- 1977-06-16 CA CA000280699A patent/CA1316171C/en not_active Expired - Fee Related
- 1977-06-17 DK DK270377A patent/DK159783C/da active
- 1977-06-17 US US05/807,409 patent/US4264595A/en not_active Expired - Lifetime
- 1977-06-20 GR GR53748A patent/GR63635B/el unknown
- 1977-06-20 NO NO772170A patent/NO772170L/no unknown
- 1977-06-20 GB GB25739/77A patent/GB1587941A/en not_active Expired
- 1977-06-21 DE DE19772727753 patent/DE2727753A1/de active Granted
- 1977-06-21 DE DE2760271A patent/DE2760271C2/de not_active Expired
- 1977-06-21 DE DE2760448A patent/DE2760448C2/de not_active Expired
- 1977-06-21 AU AU26271/77A patent/AU508551B2/en not_active Expired
- 1977-06-21 SE SE7707176A patent/SE464581B/xx not_active IP Right Cessation
- 1977-06-22 FI FI771951A patent/FI67384C/fi not_active IP Right Cessation
- 1977-06-22 AT AT442477A patent/AT352277B/de not_active IP Right Cessation
- 1977-06-22 HU HU77TA1446A patent/HU182053B/hu unknown
- 1977-06-23 FR FR7719340A patent/FR2408612A1/fr active Granted
- 1977-06-23 ZA ZA00773775A patent/ZA773775B/xx unknown
- 1977-06-23 BE BE178725A patent/BE856045A/xx not_active IP Right Cessation
- 1977-06-24 CH CH779977A patent/CH629813A5/de not_active IP Right Cessation
- 1977-06-27 PH PH19915A patent/PH15144A/en unknown
- 1977-06-27 NL NLAANVRAGE7707129,A patent/NL189354C/xx not_active IP Right Cessation
- 1977-06-27 ES ES460124A patent/ES460124A1/es not_active Expired
- 1977-06-28 PT PT66735A patent/PT66735B/pt unknown
- 1977-07-23 MX MX775834U patent/MX5198E/es unknown
-
1978
- 1978-06-14 ES ES470782A patent/ES470782A1/es not_active Expired
-
1981
- 1981-07-16 CH CH468381A patent/CH630386A5/de not_active IP Right Cessation
- 1981-07-16 CH CH468481A patent/CH630923A5/de not_active IP Right Cessation
-
1982
- 1982-01-13 CH CH18882A patent/CH634578A5/de not_active IP Right Cessation
- 1982-05-11 PH PH27261A patent/PH19543A/en unknown
-
1989
- 1989-12-08 DK DK621189A patent/DK161081C/da active
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