BE823861A - Derives de cephalosporine - Google Patents
Derives de cephalosporineInfo
- Publication number
- BE823861A BE823861A BE1006358A BE1006358A BE823861A BE 823861 A BE823861 A BE 823861A BE 1006358 A BE1006358 A BE 1006358A BE 1006358 A BE1006358 A BE 1006358A BE 823861 A BE823861 A BE 823861A
- Authority
- BE
- Belgium
- Prior art keywords
- emi
- group
- compound
- compound according
- formula
- Prior art date
Links
- 229930186147 Cephalosporin Natural products 0.000 title description 21
- 229940124587 cephalosporin Drugs 0.000 title description 21
- 150000001780 cephalosporins Chemical class 0.000 title description 20
- 150000001875 compounds Chemical class 0.000 claims description 122
- -1 amino, mercapto, hydroxyl Chemical group 0.000 claims description 96
- 238000000034 method Methods 0.000 claims description 83
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 61
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 47
- 238000006243 chemical reaction Methods 0.000 claims description 43
- 239000002253 acid Substances 0.000 claims description 42
- 229910052757 nitrogen Inorganic materials 0.000 claims description 35
- 230000008569 process Effects 0.000 claims description 32
- 150000003839 salts Chemical class 0.000 claims description 25
- 125000000217 alkyl group Chemical group 0.000 claims description 24
- 150000002148 esters Chemical class 0.000 claims description 19
- 238000004519 manufacturing process Methods 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- 125000003282 alkyl amino group Chemical group 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 239000001301 oxygen Substances 0.000 claims description 8
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 claims description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 238000007363 ring formation reaction Methods 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 239000011593 sulfur Substances 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 125000004423 acyloxy group Chemical group 0.000 claims description 5
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Chemical group 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000006239 protecting group Chemical group 0.000 claims description 5
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 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 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 230000000694 effects Effects 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 3
- 125000004434 sulfur atom Chemical group 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 3
- 125000004442 acylamino group Chemical group 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 230000008878 coupling Effects 0.000 claims description 2
- 238000010168 coupling process Methods 0.000 claims description 2
- 238000005859 coupling reaction Methods 0.000 claims description 2
- 125000002720 diazolyl group Chemical group 0.000 claims description 2
- 230000008030 elimination Effects 0.000 claims description 2
- 238000003379 elimination reaction Methods 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
- 125000001271 cephalosporin group Chemical group 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims 1
- 238000012986 modification Methods 0.000 claims 1
- 230000004048 modification Effects 0.000 claims 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims 1
- 125000001715 oxadiazolyl group Chemical group 0.000 claims 1
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims 1
- 230000035943 smell Effects 0.000 claims 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 1
- 150000004867 thiadiazoles Chemical class 0.000 claims 1
- 125000001113 thiadiazolyl group Chemical group 0.000 claims 1
- 125000001425 triazolyl group Chemical group 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 84
- 239000000243 solution Substances 0.000 description 79
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 70
- 239000000203 mixture Substances 0.000 description 59
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 58
- 239000000047 product Substances 0.000 description 45
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 35
- 235000017557 sodium bicarbonate Nutrition 0.000 description 35
- 239000013078 crystal Substances 0.000 description 34
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- 239000002904 solvent Substances 0.000 description 30
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 29
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 28
- 239000011541 reaction mixture Substances 0.000 description 26
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 239000007864 aqueous solution Substances 0.000 description 24
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- 238000001816 cooling Methods 0.000 description 21
- 239000011734 sodium Substances 0.000 description 21
- 229910052708 sodium Inorganic materials 0.000 description 21
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- 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 18
- 238000001914 filtration Methods 0.000 description 17
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 14
- 239000002585 base Substances 0.000 description 14
- 229920001429 chelating resin Polymers 0.000 description 13
- 238000004587 chromatography analysis Methods 0.000 description 13
- 238000004821 distillation Methods 0.000 description 13
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 229920005990 polystyrene resin Polymers 0.000 description 12
- 239000011780 sodium chloride Substances 0.000 description 12
- 238000001228 spectrum Methods 0.000 description 12
- 229910052783 alkali metal Inorganic materials 0.000 description 11
- 230000008014 freezing Effects 0.000 description 11
- 238000007710 freezing Methods 0.000 description 11
- 238000010438 heat treatment Methods 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- 239000011259 mixed solution Substances 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 238000002844 melting Methods 0.000 description 9
- 230000008018 melting Effects 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 150000003573 thiols Chemical class 0.000 description 9
- 239000012141 concentrate Substances 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 238000000967 suction filtration Methods 0.000 description 8
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 7
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 7
- 150000001340 alkali metals Chemical class 0.000 description 7
- 230000000844 anti-bacterial effect Effects 0.000 description 7
- 238000000354 decomposition reaction Methods 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- 239000008055 phosphate buffer solution Substances 0.000 description 7
- 239000011591 potassium Substances 0.000 description 7
- 229960003975 potassium Drugs 0.000 description 7
- 229910052700 potassium Inorganic materials 0.000 description 7
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 6
- HSHGZXNAXBPPDL-HZGVNTEJSA-N 7beta-aminocephalosporanic acid Chemical compound S1CC(COC(=O)C)=C(C([O-])=O)N2C(=O)[C@@H]([NH3+])[C@@H]12 HSHGZXNAXBPPDL-HZGVNTEJSA-N 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 5
- 238000002814 agar dilution Methods 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 238000002329 infrared spectrum Methods 0.000 description 5
- 239000008363 phosphate buffer Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 150000008064 anhydrides Chemical class 0.000 description 4
- 230000000845 anti-microbial effect Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical compound C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- WASQWSOJHCZDFK-UHFFFAOYSA-N diketene Chemical compound C=C1CC(=O)O1 WASQWSOJHCZDFK-UHFFFAOYSA-N 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000000921 elemental analysis Methods 0.000 description 3
- 239000002024 ethyl acetate extract Substances 0.000 description 3
- 230000001747 exhibiting effect Effects 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
- 239000011736 potassium bicarbonate Substances 0.000 description 3
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 3
- 235000015497 potassium bicarbonate Nutrition 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 235000011181 potassium carbonates Nutrition 0.000 description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 235000017550 sodium carbonate Nutrition 0.000 description 3
- JPJKQVVKHIZICB-FYZOBXCZSA-M sodium;(6r)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound [Na+].[O-]C(=O)C1=CCS[C@@H]2CC(=O)N12 JPJKQVVKHIZICB-FYZOBXCZSA-M 0.000 description 3
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 3
- CFGDUGSIBUXRMR-UHFFFAOYSA-N 1,2-dihydropyrrol-2-ide Chemical compound C=1C=[C-]NC=1 CFGDUGSIBUXRMR-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- XOHZHMUQBFJTNH-UHFFFAOYSA-N 1-methyl-2h-tetrazole-5-thione Chemical compound CN1N=NN=C1S XOHZHMUQBFJTNH-UHFFFAOYSA-N 0.000 description 2
- DWRAHCQFYGIIOW-UHFFFAOYSA-N 2-(2-oxo-3h-1,3-thiazol-4-yl)acetic acid Chemical compound OC(=O)CC1=CSC(=O)N1 DWRAHCQFYGIIOW-UHFFFAOYSA-N 0.000 description 2
- VKONPNAILGGMSR-UHFFFAOYSA-N 2-(2-sulfanylidene-3h-1,3-thiazol-4-yl)acetic acid Chemical compound OC(=O)CC1=CSC(=S)N1 VKONPNAILGGMSR-UHFFFAOYSA-N 0.000 description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- PDQAZBWRQCGBEV-UHFFFAOYSA-N Ethylenethiourea Chemical compound S=C1NCCN1 PDQAZBWRQCGBEV-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- 241000588772 Morganella morganii Species 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
- 241000588767 Proteus vulgaris Species 0.000 description 2
- ATPFRGQBOVFFQM-WJIDAKASSA-N [(1s,3r,7r,8r,8as)-3-(hydroxymethyl)-8-[2-[(2r,4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] 2,2-dimethylbutanoate Chemical compound C([C@@H]1[C@H](C)C=CC2=C[C@H](CO)C[C@@H]([C@@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 ATPFRGQBOVFFQM-WJIDAKASSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- YNNGZCVDIREDDK-UHFFFAOYSA-N aminocarbamodithioic acid Chemical compound NNC(S)=S YNNGZCVDIREDDK-UHFFFAOYSA-N 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- HOKIDJSKDBPKTQ-GLXFQSAKSA-N cephalosporin C Chemical compound S1CC(COC(=O)C)=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CCC[C@@H](N)C(O)=O)[C@@H]12 HOKIDJSKDBPKTQ-GLXFQSAKSA-N 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- MJEMIOXXNCZZFK-UHFFFAOYSA-N ethylone Chemical compound CCNC(C)C(=O)C1=CC=C2OCOC2=C1 MJEMIOXXNCZZFK-UHFFFAOYSA-N 0.000 description 2
- 239000012456 homogeneous solution Substances 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 229910052500 inorganic mineral Chemical class 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 2
- 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 2
- 239000011707 mineral Chemical class 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 229940007042 proteus vulgaris Drugs 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
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- 230000037396 body weight Effects 0.000 description 1
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- GNVMUORYQLCPJZ-UHFFFAOYSA-N carbamothioic s-acid Chemical compound NC(S)=O GNVMUORYQLCPJZ-UHFFFAOYSA-N 0.000 description 1
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- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
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- CXHHBNMLPJOKQD-UHFFFAOYSA-N methyl hydrogen carbonate Chemical compound COC(O)=O CXHHBNMLPJOKQD-UHFFFAOYSA-N 0.000 description 1
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- 230000000813 microbial effect Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000006011 modification reaction Methods 0.000 description 1
- 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 125000005447 octyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
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- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 239000002798 polar 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
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 1
- 229940116357 potassium thiocyanate Drugs 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000012048 reactive intermediate Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 150000003585 thioureas Chemical class 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 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
- 210000001635 urinary tract Anatomy 0.000 description 1
- 208000019206 urinary tract infection Diseases 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
-
- 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
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 (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP741521A JPS57873B2 (en, 2012) | 1973-12-25 | 1973-12-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BE823861A true BE823861A (fr) | 1975-06-24 |
Family
ID=11503790
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BE1006358A BE823861A (fr) | 1973-12-25 | 1974-12-24 | Derives de cephalosporine |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JPS57873B2 (en, 2012) |
| BE (1) | BE823861A (en, 2012) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4025626A (en) | 1975-12-09 | 1977-05-24 | Smithkline Corporation | 7-Acyl-3-(ureidoalkyl substituted tetrazolylthiomethyl)-cephalosporins |
| US4079134A (en) | 1976-09-24 | 1978-03-14 | Smithkline Corporation | 7-Acylamino-3-(5-sulfomethyl-1,3,4-thiadiazol-2-ylthiomethyl)-3-cephem-4-carboxylic acids |
| US4083975A (en) | 1976-09-24 | 1978-04-11 | Smithkline Corporation | 7-Acylamino-3-(3-sulfomethyl-1,2,4-triazol-5-ylthiomethyl)-3-cephem-4-carboxylic acids |
| US4112088A (en) * | 1976-03-11 | 1978-09-05 | Smithkline Corporation | 7-Acyl-3-(sulfoalkyl substituted oxadiazolylthiomethyl) cephalosporins |
| US4118490A (en) | 1976-05-19 | 1978-10-03 | Smithkline Corporation | 7-Acyl-3-(sulfonic acid and sulfamoyl substituted tetrazolyl thiomethyl)cephalosporins and pharmaceutical compositions containing them |
| US4161527A (en) * | 1976-08-31 | 1979-07-17 | Takeda Chemical Industries, Ltd. | Antibiotic compositions |
| US4286089A (en) | 1974-12-27 | 1981-08-25 | Smithkline Corporation | 7-Acyl-3-(substituted tetrazolyl thiomethyl)cephalosporins |
| US4576937A (en) * | 1984-02-29 | 1986-03-18 | Smithkline Beckman Corporation | 7-D-Mandelamido-3(1-sulfomethyltetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid monosodium salt |
-
1973
- 1973-12-25 JP JP741521A patent/JPS57873B2/ja not_active Expired
-
1974
- 1974-12-24 BE BE1006358A patent/BE823861A/fr not_active IP Right Cessation
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4286089A (en) | 1974-12-27 | 1981-08-25 | Smithkline Corporation | 7-Acyl-3-(substituted tetrazolyl thiomethyl)cephalosporins |
| US4096256A (en) | 1975-12-09 | 1978-06-20 | Smithkline Corporation | 7-Acyl-3-(ureidoalkyl substituted tetrazolylthiomethyl) cephalosporins, antibacterial compositions containing them, and methods of treating bacterial infections using them |
| US4066761A (en) | 1975-12-09 | 1978-01-03 | Smithkline Corporation | 7-Acyl-3-(ureidoalkyl substituted tetrazolylthiomethyl)cephalosporins |
| US4068073A (en) | 1975-12-09 | 1978-01-10 | Smithkline Corporation | 7-Amino intermediates for preparing 7-acyl-3-(ureidoalkyl substituted tetrazolylthiomethyl)-cephalosporins |
| US4025626A (en) | 1975-12-09 | 1977-05-24 | Smithkline Corporation | 7-Acyl-3-(ureidoalkyl substituted tetrazolylthiomethyl)-cephalosporins |
| US4130644A (en) | 1976-03-11 | 1978-12-19 | Smithkline Corporation | 7-Acylamine-3-(sulfoalkyl substituted oxadiazolylthiomethyl) cephalosporins and pharmaceutical compositions containing them |
| US4112088A (en) * | 1976-03-11 | 1978-09-05 | Smithkline Corporation | 7-Acyl-3-(sulfoalkyl substituted oxadiazolylthiomethyl) cephalosporins |
| US4138556A (en) | 1976-03-11 | 1979-02-06 | Smithkline Corporation | 7-Amino-3-(sulfoalkyl substituted oxadiazolylthiomethyl) cephalosporins |
| US4118490A (en) | 1976-05-19 | 1978-10-03 | Smithkline Corporation | 7-Acyl-3-(sulfonic acid and sulfamoyl substituted tetrazolyl thiomethyl)cephalosporins and pharmaceutical compositions containing them |
| US4161527A (en) * | 1976-08-31 | 1979-07-17 | Takeda Chemical Industries, Ltd. | Antibiotic compositions |
| US4241057A (en) * | 1976-08-31 | 1980-12-23 | Takeda Chemical Industries, Ltd. | Antibiotic compositions |
| US4128722A (en) | 1976-09-24 | 1978-12-05 | Smithkline Corporation | 7-Trifluoromethylthioacetamido-3-(3-sulfomethyl-1,2,4-triazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid |
| US4083975A (en) | 1976-09-24 | 1978-04-11 | Smithkline Corporation | 7-Acylamino-3-(3-sulfomethyl-1,2,4-triazol-5-ylthiomethyl)-3-cephem-4-carboxylic acids |
| US4079134A (en) | 1976-09-24 | 1978-03-14 | Smithkline Corporation | 7-Acylamino-3-(5-sulfomethyl-1,3,4-thiadiazol-2-ylthiomethyl)-3-cephem-4-carboxylic acids |
| US4576937A (en) * | 1984-02-29 | 1986-03-18 | Smithkline Beckman Corporation | 7-D-Mandelamido-3(1-sulfomethyltetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid monosodium salt |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS57873B2 (en, 2012) | 1982-01-08 |
| AU7648874A (en) | 1976-06-17 |
| JPS5095293A (en, 2012) | 1975-07-29 |
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| Date | Code | Title | Description |
|---|---|---|---|
| RE20 | Patent expired |
Owner name: TAKEDA CHEMICAL INDUSTRIES LTD Effective date: 19941224 |