SE438338B - 7alfa-metoxi-7beta-(1,3-ditietan-2-karboxamido)-cefalosporansyraderivat med antibakteriell verkan - Google Patents
7alfa-metoxi-7beta-(1,3-ditietan-2-karboxamido)-cefalosporansyraderivat med antibakteriell verkanInfo
- Publication number
- SE438338B SE438338B SE7806711A SE7806711A SE438338B SE 438338 B SE438338 B SE 438338B SE 7806711 A SE7806711 A SE 7806711A SE 7806711 A SE7806711 A SE 7806711A SE 438338 B SE438338 B SE 438338B
- Authority
- SE
- Sweden
- Prior art keywords
- group
- mixture
- carboxylic acid
- methoxy
- cephem
- Prior art date
Links
- 230000000844 anti-bacterial effect Effects 0.000 title description 5
- -1 4-substituted methylene-1,3-dithietan-2-yl Chemical group 0.000 claims description 101
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 63
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 49
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 40
- 150000001875 compounds Chemical class 0.000 claims description 39
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 20
- IKWLIQXIPRUIDU-ZCFIWIBFSA-N (6r)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound OC(=O)C1=CCS[C@@H]2CC(=O)N12 IKWLIQXIPRUIDU-ZCFIWIBFSA-N 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- OMAFFHIGWTVZOH-UHFFFAOYSA-N 1-methyltetrazole Chemical compound CN1C=NN=N1 OMAFFHIGWTVZOH-UHFFFAOYSA-N 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
- 125000001113 thiadiazolyl group Chemical class 0.000 claims description 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 4
- 125000003831 tetrazolyl group Chemical class 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 194
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 148
- 239000000243 solution Substances 0.000 description 124
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 111
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 105
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 78
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 75
- 239000011541 reaction mixture Substances 0.000 description 74
- 239000002904 solvent Substances 0.000 description 60
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 57
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 55
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 54
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 54
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 53
- 238000006243 chemical reaction Methods 0.000 description 49
- 239000000047 product Substances 0.000 description 49
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 45
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 44
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 39
- 239000000741 silica gel Substances 0.000 description 39
- 229910002027 silica gel Inorganic materials 0.000 description 39
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 38
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 37
- 238000001816 cooling Methods 0.000 description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
- 239000003480 eluent Substances 0.000 description 33
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 27
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 26
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 25
- 238000003756 stirring Methods 0.000 description 25
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 23
- 239000002244 precipitate Substances 0.000 description 23
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 22
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 21
- 238000001914 filtration Methods 0.000 description 21
- 239000000284 extract Substances 0.000 description 19
- 239000011780 sodium chloride Substances 0.000 description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 18
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 18
- 229920006395 saturated elastomer Polymers 0.000 description 17
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 17
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 16
- 239000002253 acid Substances 0.000 description 15
- 239000010410 layer Substances 0.000 description 14
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 14
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 13
- 239000012312 sodium hydride Substances 0.000 description 13
- 229910000104 sodium hydride Inorganic materials 0.000 description 13
- WAVQOKDKPHYRDY-GOSISDBHSA-N benzhydryl (6r)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C([C@H]1SCC=2)C(=O)N1C=2C(=O)OC(C=1C=CC=CC=1)C1=CC=CC=C1 WAVQOKDKPHYRDY-GOSISDBHSA-N 0.000 description 12
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 11
- 229910052757 nitrogen Inorganic materials 0.000 description 11
- 238000001228 spectrum Methods 0.000 description 11
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 10
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 10
- 239000005457 ice water Substances 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 9
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- MCNTVFNKNAAKPJ-UHFFFAOYSA-N potassium;2-methylpropan-2-ol;2-methylpropan-2-olate Chemical compound [K+].CC(C)(C)O.CC(C)(C)[O-] MCNTVFNKNAAKPJ-UHFFFAOYSA-N 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- QYYJXSLRNKUWLE-UHFFFAOYSA-M sodium;2,2-diiodoacetate Chemical compound [Na+].[O-]C(=O)C(I)I QYYJXSLRNKUWLE-UHFFFAOYSA-M 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- 235000019253 formic acid Nutrition 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 5
- 229930186147 Cephalosporin Natural products 0.000 description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 229940124587 cephalosporin Drugs 0.000 description 5
- 229960005215 dichloroacetic acid Drugs 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 5
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- 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 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 235000011089 carbon dioxide Nutrition 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000012259 ether extract Substances 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 3
- UYYCVBASZNFFRX-UHFFFAOYSA-N n-propan-2-ylcyclohexanamine Chemical compound CC(C)NC1CCCCC1 UYYCVBASZNFFRX-UHFFFAOYSA-N 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 3
- HDQNRAARHOPGQZ-UHFFFAOYSA-N tert-butyl 4-(2-amino-1-cyano-2-oxoethylidene)-1,3-dithietane-2-carboxylate Chemical compound CC(C)(C)OC(=O)C1SC(=C(C#N)C(N)=O)S1 HDQNRAARHOPGQZ-UHFFFAOYSA-N 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- XOHZHMUQBFJTNH-UHFFFAOYSA-N 1-methyl-2h-tetrazole-5-thione Chemical compound CN1N=NN=C1S XOHZHMUQBFJTNH-UHFFFAOYSA-N 0.000 description 2
- BQAMFNQVNXPFFH-UHFFFAOYSA-N 2,2-diiodoacetic acid Chemical compound OC(=O)C(I)I BQAMFNQVNXPFFH-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- POXIZPBFFUKMEQ-UHFFFAOYSA-N 2-cyanoethenylideneazanide Chemical group [N-]=C=[C+]C#N POXIZPBFFUKMEQ-UHFFFAOYSA-N 0.000 description 2
- KILJAPIOVXDLDO-UHFFFAOYSA-N 4-[1-(methylamino)-3-[(2-methylpropan-2-yl)oxy]-1,3-dioxopropan-2-ylidene]-1,3-dithietane-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)C(C(=O)NC)=C1SC(C(O)=O)S1 KILJAPIOVXDLDO-UHFFFAOYSA-N 0.000 description 2
- YPSAHJVIBAAQEP-UHFFFAOYSA-N 4-[1-[(2-methylpropan-2-yl)oxy]-1,3-dioxo-3-phenylpropan-2-ylidene]-1,3-dithietane-2-carboxylic acid Chemical compound S1C(C(O)=O)SC1=C(C(=O)OC(C)(C)C)C(=O)C1=CC=CC=C1 YPSAHJVIBAAQEP-UHFFFAOYSA-N 0.000 description 2
- QONOUXVTTLIKFP-UHFFFAOYSA-N 4-[1-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-ylidene]-1,3-dithietane-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)C(C)=C1SC(C(O)=O)S1 QONOUXVTTLIKFP-UHFFFAOYSA-N 0.000 description 2
- SWBNKLMVDYYRMC-UHFFFAOYSA-N 4-[1-methoxy-2-[(2-methylpropan-2-yl)oxy]-2-oxoethylidene]-1,3-dithietane-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)C(OC)=C1SC(C(O)=O)S1 SWBNKLMVDYYRMC-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- 241000588769 Proteus <enterobacteria> Species 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- ITLHXEGAYQFOHJ-UHFFFAOYSA-N [diazo(phenyl)methyl]benzene Chemical compound C=1C=CC=CC=1C(=[N+]=[N-])C1=CC=CC=C1 ITLHXEGAYQFOHJ-UHFFFAOYSA-N 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 125000005907 alkyl ester group Chemical group 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 229940043279 diisopropylamine Drugs 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000002024 ethyl acetate extract Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000002198 insoluble material Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- KDGSZJXXQWMOKP-UHFFFAOYSA-M potassium;2,2-dichloroacetate Chemical compound [K+].[O-]C(=O)C(Cl)Cl KDGSZJXXQWMOKP-UHFFFAOYSA-M 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 235000017550 sodium carbonate Nutrition 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 1
- 125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 description 1
- 125000004521 1,3,4-thiadiazol-2-yl group Chemical group S1C(=NN=C1)* 0.000 description 1
- 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 1
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 1
- HRWBGLRXDDPRSB-UHFFFAOYSA-N 1,3-dithietane-2-carboxylic acid Chemical compound OC(=O)C1SCS1 HRWBGLRXDDPRSB-UHFFFAOYSA-N 0.000 description 1
- GUSZGQOKIPANHR-UHFFFAOYSA-N 2,2-dimethylpropylsulfonyl acetate Chemical compound C(C)(=O)OS(=O)(=O)CC(C)(C)C GUSZGQOKIPANHR-UHFFFAOYSA-N 0.000 description 1
- DHQLWKZANUWLGP-UHFFFAOYSA-N 2h-pyran-6-carbaldehyde Chemical compound O=CC1=CC=CCO1 DHQLWKZANUWLGP-UHFFFAOYSA-N 0.000 description 1
- NGXAKOSHFSBAKX-UHFFFAOYSA-N 4-(1,3-dimethoxy-1,3-dioxopropan-2-ylidene)-1,3-dithietane-2-carboxylic acid Chemical compound COC(=O)C(C(=O)OC)=C1SC(C(O)=O)S1 NGXAKOSHFSBAKX-UHFFFAOYSA-N 0.000 description 1
- OZKBRTCNNQZHKI-UHFFFAOYSA-N 4-(1-amino-1,3-dioxobutan-2-ylidene)-1,3-dithietane-2-carboxylic acid Chemical compound CC(=O)C(C(N)=O)=C1SC(C(O)=O)S1 OZKBRTCNNQZHKI-UHFFFAOYSA-N 0.000 description 1
- XWXRQXCHOKQYQT-UHFFFAOYSA-N 4-(2-amino-1-cyano-2-oxoethylidene)-1,3-dithietane-2-carboxylic acid Chemical compound NC(=O)C(C#N)=C1SC(C(O)=O)S1 XWXRQXCHOKQYQT-UHFFFAOYSA-N 0.000 description 1
- YHCMKNTUMGIIKG-UHFFFAOYSA-N 4-(2-benzhydryloxy-2-oxo-1-sulfamoylethylidene)-1,3-dithietane-2-carboxylic acid Chemical compound S1C(C(O)=O)SC1=C(S(=O)(=O)N)C(=O)OC(C=1C=CC=CC=1)C1=CC=CC=C1 YHCMKNTUMGIIKG-UHFFFAOYSA-N 0.000 description 1
- PCOCFIOYWNCGBM-UHFFFAOYSA-N 4-[(2-methylpropan-2-yl)oxy]-4-oxobutanoic acid Chemical compound CC(C)(C)OC(=O)CCC(O)=O PCOCFIOYWNCGBM-UHFFFAOYSA-N 0.000 description 1
- WCIYFKGUQVSXGG-UHFFFAOYSA-N 4-[1,3-bis[(2-methylpropan-2-yl)oxy]-1,3-dioxopropan-2-ylidene]-1,3-dithietane-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)C(C(=O)OC(C)(C)C)=C1SC(C(O)=O)S1 WCIYFKGUQVSXGG-UHFFFAOYSA-N 0.000 description 1
- JRPBOTGSAJBDNX-UHFFFAOYSA-N 4-[1,4-bis[(2-methylpropan-2-yl)oxy]-1,4-dioxobutan-2-ylidene]-1,3-dithietane-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)CC(C(=O)OC(C)(C)C)=C1SC(C(O)=O)S1 JRPBOTGSAJBDNX-UHFFFAOYSA-N 0.000 description 1
- HQXYBKKFYSDDAD-UHFFFAOYSA-N 4-[1-(dimethylamino)-3-[(2-methylpropan-2-yl)oxy]-1,3-dioxopropan-2-ylidene]-1,3-dithietane-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)C(C(=O)N(C)C)=C1SC(C(O)=O)S1 HQXYBKKFYSDDAD-UHFFFAOYSA-N 0.000 description 1
- PAZAMGSRLAVTOA-UHFFFAOYSA-N 4-[1-[(2-methylpropan-2-yl)oxy]-1,3-dioxobutan-2-ylidene]-1,3-dithietane-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)C(C(=O)C)=C1SC(C(O)=O)S1 PAZAMGSRLAVTOA-UHFFFAOYSA-N 0.000 description 1
- JPRLRPJFVJZQBK-UHFFFAOYSA-N 4-[1-[(2-methylpropan-2-yl)oxy]-1-oxobutan-2-ylidene]-1,3-dithietane-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)C(CC)=C1SC(C(O)=O)S1 JPRLRPJFVJZQBK-UHFFFAOYSA-N 0.000 description 1
- HPWIIVAFSQSWBT-UHFFFAOYSA-N 4-[1-ethylsulfanyl-2-[(2-methylpropan-2-yl)oxy]-2-oxoethylidene]-1,3-dithietane-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)C(SCC)=C1SC(C(O)=O)S1 HPWIIVAFSQSWBT-UHFFFAOYSA-N 0.000 description 1
- JBJYUUZCIMJVME-UHFFFAOYSA-N 4-[2-[(2-methylpropan-2-yl)oxy]-1-methylsulfonyl-2-oxoethylidene]-1,3-dithietane-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)C(S(C)(=O)=O)=C1SC(C(O)=O)S1 JBJYUUZCIMJVME-UHFFFAOYSA-N 0.000 description 1
- ANHVSAPHVZZDQR-UHFFFAOYSA-N 4-[2-[(2-methylpropan-2-yl)oxy]-2-oxo-1-phenylethylidene]-1,3-dithietane-2-carboxylic acid Chemical compound C=1C=CC=CC=1C(C(=O)OC(C)(C)C)=C1SC(C(O)=O)S1 ANHVSAPHVZZDQR-UHFFFAOYSA-N 0.000 description 1
- MBERGHJPIMJRJM-UHFFFAOYSA-N 4-[2-[(2-methylpropan-2-yl)oxy]-2-oxo-1-pyridin-3-ylethylidene]-1,3-dithietane-2-carboxylic acid Chemical compound C=1C=CN=CC=1C(C(=O)OC(C)(C)C)=C1SC(C(O)=O)S1 MBERGHJPIMJRJM-UHFFFAOYSA-N 0.000 description 1
- HEOSKYHNHYNBNQ-UHFFFAOYSA-N 4-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethylidene]-1,3-dithietane-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)C=C1SC(C(O)=O)S1 HEOSKYHNHYNBNQ-UHFFFAOYSA-N 0.000 description 1
- VUTBELPREDJDDH-UHFFFAOYSA-N 4-amino-5-hydroxymethyl-2-methylpyrimidine Chemical compound CC1=NC=C(CO)C(N)=N1 VUTBELPREDJDDH-UHFFFAOYSA-N 0.000 description 1
- XZGLNCKSNVGDNX-UHFFFAOYSA-N 5-methyl-2h-tetrazole Chemical compound CC=1N=NNN=1 XZGLNCKSNVGDNX-UHFFFAOYSA-N 0.000 description 1
- FPVUWZFFEGYCGB-UHFFFAOYSA-N 5-methyl-3h-1,3,4-thiadiazole-2-thione Chemical compound CC1=NN=C(S)S1 FPVUWZFFEGYCGB-UHFFFAOYSA-N 0.000 description 1
- 229930184397 7-Methoxycephalosporin Natural products 0.000 description 1
- 241001421185 Anomis Species 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- GNJZBMCFBSAYQQ-UHFFFAOYSA-N C(C)(=O)OS(NC(C1=CC=CC=C1)C1=CC=CC=C1)(=O)=O Chemical compound C(C)(=O)OS(NC(C1=CC=CC=C1)C1=CC=CC=C1)(=O)=O GNJZBMCFBSAYQQ-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 206010010071 Coma Diseases 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- 241000588722 Escherichia Species 0.000 description 1
- 241000588748 Klebsiella Species 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 1
- 108091033411 PCA3 Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- UMGULAKGAOXNDK-UHFFFAOYSA-N [O-]C([S+]1SCC1)=O Chemical compound [O-]C([S+]1SCC1)=O UMGULAKGAOXNDK-UHFFFAOYSA-N 0.000 description 1
- GCPWJFKTWGFEHH-UHFFFAOYSA-N acetoacetamide Chemical compound CC(=O)CC(N)=O GCPWJFKTWGFEHH-UHFFFAOYSA-N 0.000 description 1
- MATIBSILLGNSON-UHFFFAOYSA-N acetyl 2-tert-butylbenzoate Chemical compound C(C)(=O)OC(C1=C(C=CC=C1)C(C)(C)C)=O MATIBSILLGNSON-UHFFFAOYSA-N 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 1
- 125000005036 alkoxyphenyl group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000005518 carboxamido group Chemical group 0.000 description 1
- 125000004181 carboxyalkyl group Chemical group 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 229930002875 chlorophyll Natural products 0.000 description 1
- 235000019804 chlorophyll Nutrition 0.000 description 1
- ATNHDLDRLWWWCB-AENOIHSZSA-M chlorophyll a Chemical compound C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC(C(CC)=C3C)=[N+]4C3=CC3=C(C=C)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 ATNHDLDRLWWWCB-AENOIHSZSA-M 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- YRJBXAMFOGNVCP-UHFFFAOYSA-L disodium 3-amino-2-cyano-3-oxoprop-1-ene-1,1-dithiolate Chemical compound [Na+].[Na+].NC(=O)C(C#N)=C([S-])[S-] YRJBXAMFOGNVCP-UHFFFAOYSA-L 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000006345 epimerization reaction Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 125000004464 hydroxyphenyl group Chemical group 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- SBMNMKRUXIRDFB-UHFFFAOYSA-N o-tert-butyl butanethioate Chemical compound CCCC(=S)OC(C)(C)C SBMNMKRUXIRDFB-UHFFFAOYSA-N 0.000 description 1
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 208000003383 pontocerebellar hypoplasia type 3 Diseases 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- ZUFQCVZBBNZMKD-UHFFFAOYSA-M potassium 2-ethylhexanoate Chemical compound [K+].CCCCC(CC)C([O-])=O ZUFQCVZBBNZMKD-UHFFFAOYSA-M 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
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000003507 refrigerant Substances 0.000 description 1
- 229940080263 sodium dichloroacetate Drugs 0.000 description 1
- 229910052979 sodium sulfide Inorganic materials 0.000 description 1
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
- QIDXIFUFBHTWTQ-UHFFFAOYSA-M sodium;2,2-dibromoacetate Chemical compound [Na+].[O-]C(=O)C(Br)Br QIDXIFUFBHTWTQ-UHFFFAOYSA-M 0.000 description 1
- LUPNKHXLFSSUGS-UHFFFAOYSA-M sodium;2,2-dichloroacetate Chemical compound [Na+].[O-]C(=O)C(Cl)Cl LUPNKHXLFSSUGS-UHFFFAOYSA-M 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000002195 soluble material Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- WVNZGIJOOOHIPU-UHFFFAOYSA-N tert-butyl 2,2-dibromoacetate Chemical compound CC(C)(C)OC(=O)C(Br)Br WVNZGIJOOOHIPU-UHFFFAOYSA-N 0.000 description 1
- IKSREAYYPUBCFL-UHFFFAOYSA-N tert-butyl 2-[4-[(2-methylpropan-2-yl)oxy]phenyl]acetate Chemical compound CC(C)(C)OC(=O)CC1=CC=C(OC(C)(C)C)C=C1 IKSREAYYPUBCFL-UHFFFAOYSA-N 0.000 description 1
- JSWGISCKHSCBGX-UHFFFAOYSA-N tert-butyl 2-methoxyacetate Chemical compound COCC(=O)OC(C)(C)C JSWGISCKHSCBGX-UHFFFAOYSA-N 0.000 description 1
- QROFQHQXTMKORN-UHFFFAOYSA-N tert-butyl 2-phenylacetate Chemical compound CC(C)(C)OC(=O)CC1=CC=CC=C1 QROFQHQXTMKORN-UHFFFAOYSA-N 0.000 description 1
- BARPQIZUSOWBIZ-UHFFFAOYSA-N tert-butyl 3-(dimethylamino)-3-oxopropanoate Chemical compound CN(C)C(=O)CC(=O)OC(C)(C)C BARPQIZUSOWBIZ-UHFFFAOYSA-N 0.000 description 1
- SDLADNZVJJNWKL-UHFFFAOYSA-N tert-butyl 3-(methylamino)-3-oxopropanoate Chemical compound CNC(=O)CC(=O)OC(C)(C)C SDLADNZVJJNWKL-UHFFFAOYSA-N 0.000 description 1
- JKUYRAMKJLMYLO-UHFFFAOYSA-N tert-butyl 3-oxobutanoate Chemical compound CC(=O)CC(=O)OC(C)(C)C JKUYRAMKJLMYLO-UHFFFAOYSA-N 0.000 description 1
- DOBZABBTVQPZRR-UHFFFAOYSA-N tert-butyl 4-(dicyanomethylidene)-1,3-dithietane-2-carboxylate Chemical compound CC(C)(C)OC(=O)C1SC(=C(C#N)C#N)S1 DOBZABBTVQPZRR-UHFFFAOYSA-N 0.000 description 1
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 1
- JAELLLITIZHOGQ-UHFFFAOYSA-N tert-butyl propanoate Chemical compound CCC(=O)OC(C)(C)C JAELLLITIZHOGQ-UHFFFAOYSA-N 0.000 description 1
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 238000005406 washing Methods 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
- C07D501/36—Methylene radicals, substituted by sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D339/00—Heterocyclic compounds containing rings having two sulfur atoms as the only ring hetero atoms
-
- 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
- C07D501/57—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with a further substituent in position 7, e.g. cephamycines
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Cephalosporin Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP52068699A JPS5854157B2 (ja) | 1977-06-10 | 1977-06-10 | セフアロスポリン化合物の新規誘導体ならびにその製造方法 |
| JP9077277A JPS5811956B2 (ja) | 1977-07-28 | 1977-07-28 | 新抗菌化合物 |
| JP53010772A JPS6052714B2 (ja) | 1978-02-02 | 1978-02-02 | 新規抗菌化合物 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SE7806711L SE7806711L (sv) | 1978-12-11 |
| SE438338B true SE438338B (sv) | 1985-04-15 |
Family
ID=27279078
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SE7806711A SE438338B (sv) | 1977-06-10 | 1978-06-09 | 7alfa-metoxi-7beta-(1,3-ditietan-2-karboxamido)-cefalosporansyraderivat med antibakteriell verkan |
Country Status (11)
| Country | Link |
|---|---|
| US (3) | US4263432A (de) |
| CA (1) | CA1103659A (de) |
| CH (1) | CH648317A5 (de) |
| DE (1) | DE2824559C2 (de) |
| DK (1) | DK164224C (de) |
| ES (4) | ES470689A1 (de) |
| FR (1) | FR2405952A1 (de) |
| IT (1) | IT1159721B (de) |
| MX (1) | MX5137E (de) |
| NL (2) | NL185622C (de) |
| SE (1) | SE438338B (de) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2824559C2 (de) * | 1977-06-10 | 1985-01-10 | Yamanouchi Pharmaceutical Co., Ltd., Tokio / Tokyo | 7α-Methoxy-7β-(4-substituierte-methylen-1,3-dithietan-2-yl)-carboxamido-3-Δ↑3↑-cephem-4-carbonsäuren, Verfahren zu deren Herstellung sowie ihre Verwendung |
| GB1604738A (en) * | 1977-07-28 | 1981-12-16 | Yamanouchi Pharma Co Ltd | 1,3-dithietane-2-carboxylic acid derivatives and the preparation thereof |
| EP0062118B1 (de) * | 1981-04-03 | 1986-07-09 | Nihon Nohyaku Co., Ltd. | Verfahren zur Herstellung von 1,3-Dithiol-2-yliden-malonaten |
| ATE17245T1 (de) * | 1981-04-03 | 1986-01-15 | Nihon Nohyaku Co Ltd | Verfahren zur herstellung von dialkylestern von 1,3-dithiol-2-ylidene-malonsaeure. |
| JPS6011917B2 (ja) * | 1981-04-09 | 1985-03-28 | 山之内製薬株式会社 | 新規なセファロスポリン化合物 |
| US5147871A (en) * | 1986-07-03 | 1992-09-15 | Hoffmann La-Roche, Inc. | Anti-bacterial cephalosporin compounds |
| US5336768A (en) * | 1988-05-24 | 1994-08-09 | Hoffmann-La Roche Inc. | Antibacterial cephalosporin compounds |
| CS273349B2 (en) * | 1988-03-31 | 1991-03-12 | Hoffmann La Roche | Method of cephalosporin's new derivatives production |
| US5162523A (en) * | 1989-07-21 | 1992-11-10 | Hoffmann-La Roche Inc. | Cephalosporin antibacterial compounds |
| US5159077A (en) * | 1989-07-21 | 1992-10-27 | Hoffmann-La Roche Inc. | Penam antibacterial compounds |
| JP2566680B2 (ja) | 1990-12-21 | 1996-12-25 | 塩野義製薬株式会社 | ビニルチオ酢酸誘導体 |
| JPH0713032B2 (ja) * | 1993-03-19 | 1995-02-15 | 工業技術院長 | ターシャリーブチルメチルエーテルの光脱水素二量化方法 |
| US5811419A (en) * | 1996-01-16 | 1998-09-22 | Hoffmann-La Roche Inc. | Isooxacephem-derivatives |
| US5883247A (en) * | 1996-06-10 | 1999-03-16 | Hoffmann-La Roche Inc. | Preparation of cephem and isooxacephem derivatives |
| ITMI20010964A1 (it) | 2001-05-10 | 2002-11-10 | Acs Dobfar Spa | Procedimento per l'ottenimento di composti utili per la produzione del cefotetan e nuovi composti cosi' ottenuti |
| ITMI20051085A1 (it) * | 2005-06-10 | 2006-12-11 | Acs Dobfar Spa | Metodo di purificazione del cefotetan |
| ITMI20051115A1 (it) * | 2005-06-14 | 2006-12-15 | Acs Dobfar Spa | Procedimento per l'ottenimento di cefotetan con resa elevata |
| WO2007122628A1 (en) * | 2006-04-21 | 2007-11-01 | Lupin Limited | Improved process for preparation of highly pure cefotetan disodium |
| CN102161669A (zh) * | 2011-02-21 | 2011-08-24 | 江苏济川制药有限公司 | 一种除去头孢替坦二钠中杂质△2-isomer的方法 |
| CN102250125B (zh) * | 2011-05-20 | 2013-10-16 | 海南合瑞制药股份有限公司 | 一种头孢替坦的制备方法 |
| CN106478670B (zh) * | 2016-08-30 | 2018-11-20 | 济川药业集团有限公司 | 一种头孢替坦酸的新结晶及其制备方法 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL29235A (en) | 1967-01-05 | 1971-10-20 | Bristol Myers Co | 7-(pyridylthioacetamido)cephalosporanic acid derivatives and their preparation |
| CH527215A (de) * | 1967-04-15 | 1972-08-31 | Fujisawa Pharmaceutical Co | Verfahren zur Herstellung von 3,7-disubstituierten Cephalosporinderivaten |
| AR205728A1 (es) * | 1973-11-14 | 1976-05-31 | Rhone Poulenc Sa | Procedimiento para preparar ((dihidro-5,6-oxa)-(di) tiino-1,4-il-2) acetamido)-7 cefalosporina y sus sales |
| OA05033A (fr) * | 1974-07-01 | 1980-12-31 | Rhone Poulenc Ind | Nouveaux dérivés de la céphalosporine et leur préparation. |
| JPS5119765A (en) * | 1974-08-09 | 1976-02-17 | Takeda Chemical Industries Ltd | Aminochiazoorujudotaino seizoho |
| JPS5530714B2 (de) * | 1974-08-22 | 1980-08-13 | ||
| US4182868A (en) * | 1974-10-29 | 1980-01-08 | Takeda Chemical Industries, Ltd. | 7-Methoxycephalosporin derivatives |
| US4203899A (en) * | 1974-12-19 | 1980-05-20 | Takeda Chemical Industries, Ltd. | Thiazolylacetamido compounds |
| DE2539214C2 (de) * | 1975-09-03 | 1984-03-29 | E.R. Squibb & Sons, Inc., 08540 Princeton, N.J. | 7-Methoxythienyl-ureido-cephalosporin und dieses enthaltendes Arzneimittel |
| US4299829A (en) * | 1976-03-12 | 1981-11-10 | Fujisawa Pharmaceutical Co., Ltd. | 2-Lower alkyl-7-substituted-2 or 3-cephem 4-carboxylic acid compounds |
| US4058609A (en) * | 1976-06-28 | 1977-11-15 | Smithkline Corporation | 7-Dithioacetamido cephalosporins |
| DE2824559C2 (de) * | 1977-06-10 | 1985-01-10 | Yamanouchi Pharmaceutical Co., Ltd., Tokio / Tokyo | 7α-Methoxy-7β-(4-substituierte-methylen-1,3-dithietan-2-yl)-carboxamido-3-Δ↑3↑-cephem-4-carbonsäuren, Verfahren zu deren Herstellung sowie ihre Verwendung |
| GB1604738A (en) * | 1977-07-28 | 1981-12-16 | Yamanouchi Pharma Co Ltd | 1,3-dithietane-2-carboxylic acid derivatives and the preparation thereof |
-
1978
- 1978-06-05 DE DE2824559A patent/DE2824559C2/de not_active Expired
- 1978-06-05 CH CH6107/78A patent/CH648317A5/de not_active IP Right Cessation
- 1978-06-07 NL NLAANVRAGE7806208,A patent/NL185622C/xx not_active IP Right Cessation
- 1978-06-07 US US05/913,500 patent/US4263432A/en not_active Expired - Lifetime
- 1978-06-08 CA CA305,045A patent/CA1103659A/en not_active Expired
- 1978-06-09 SE SE7806711A patent/SE438338B/sv not_active IP Right Cessation
- 1978-06-09 FR FR7817303A patent/FR2405952A1/fr active Granted
- 1978-06-09 ES ES470689A patent/ES470689A1/es not_active Expired
- 1978-06-09 DK DK258078A patent/DK164224C/da not_active IP Right Cessation
- 1978-06-12 IT IT68369/78A patent/IT1159721B/it active Protection Beyond IP Right Term
- 1978-06-12 MX MX787141U patent/MX5137E/es unknown
-
1979
- 1979-03-31 ES ES479167A patent/ES479167A1/es not_active Expired
- 1979-03-31 ES ES479166A patent/ES479166A1/es not_active Expired
- 1979-03-31 ES ES479168A patent/ES479168A1/es not_active Expired
-
1980
- 1980-11-19 US US06/208,298 patent/US4404373A/en not_active Ceased
-
1985
- 1985-04-25 US US06/727,233 patent/USRE32491E/en not_active Expired - Lifetime
-
1989
- 1989-05-02 NL NL8901120A patent/NL8901120A/nl active Search and Examination
Also Published As
| Publication number | Publication date |
|---|---|
| DE2824559A1 (de) | 1979-01-04 |
| CA1103659A (en) | 1981-06-23 |
| CH648317A5 (de) | 1985-03-15 |
| US4263432A (en) | 1981-04-21 |
| DK164224C (da) | 1992-10-19 |
| DK258078A (da) | 1979-01-23 |
| ES470689A1 (es) | 1979-09-01 |
| FR2405952A1 (fr) | 1979-05-11 |
| IT1159721B (it) | 1987-03-04 |
| DK164224B (da) | 1992-05-25 |
| SE7806711L (sv) | 1978-12-11 |
| USRE32491E (en) | 1987-09-01 |
| NL185622B (nl) | 1990-01-02 |
| NL7806208A (nl) | 1978-12-12 |
| DE2824559C2 (de) | 1985-01-10 |
| US4404373A (en) | 1983-09-13 |
| MX5137E (es) | 1983-03-28 |
| ES479167A1 (es) | 1979-07-01 |
| FR2405952B1 (de) | 1983-02-25 |
| ES479166A1 (es) | 1979-07-01 |
| NL8901120A (nl) | 1989-08-01 |
| NL185622C (nl) | 1990-06-01 |
| ES479168A1 (es) | 1979-07-01 |
| IT7868369A0 (it) | 1978-06-12 |
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