CA1165759A - 7.alpha.-METHOXYCEPHALOSPORIN DERIVATIVES, PROCESS FOR THE PREPARATION THEREOF AND ANTIBACTERIAL DRUGS CONTAINING THE SAME - Google Patents
7.alpha.-METHOXYCEPHALOSPORIN DERIVATIVES, PROCESS FOR THE PREPARATION THEREOF AND ANTIBACTERIAL DRUGS CONTAINING THE SAMEInfo
- Publication number
- CA1165759A CA1165759A CA000367539A CA367539A CA1165759A CA 1165759 A CA1165759 A CA 1165759A CA 000367539 A CA000367539 A CA 000367539A CA 367539 A CA367539 A CA 367539A CA 1165759 A CA1165759 A CA 1165759A
- Authority
- CA
- Canada
- Prior art keywords
- methoxy
- cephem
- carboxylic acid
- carboxamido
- dihydroxychromone
- 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
Links
- 238000000034 method Methods 0.000 title claims abstract description 50
- 230000008569 process Effects 0.000 title claims abstract description 40
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 229940124350 antibacterial drug Drugs 0.000 title abstract description 5
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 92
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 85
- 150000001875 compounds Chemical class 0.000 claims description 79
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 63
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 49
- -1 (1-carboxymethyl-5-tetrazolyl)thio Chemical group 0.000 claims description 46
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 32
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 31
- 239000002904 solvent Substances 0.000 claims description 26
- 238000006243 chemical reaction Methods 0.000 claims description 20
- 239000000126 substance Substances 0.000 claims description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 16
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 125000004423 acyloxy group Chemical group 0.000 claims description 10
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
- 159000000000 sodium salts Chemical class 0.000 claims description 9
- SIOVKLKJSOKLIF-HJWRWDBZSA-N trimethylsilyl (1z)-n-trimethylsilylethanimidate Chemical compound C[Si](C)(C)OC(/C)=N\[Si](C)(C)C SIOVKLKJSOKLIF-HJWRWDBZSA-N 0.000 claims description 9
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 7
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 7
- 239000008055 phosphate buffer solution Substances 0.000 claims description 7
- 125000004149 thio group Chemical group *S* 0.000 claims description 7
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- VYPDUQYOLCLEGS-UHFFFAOYSA-M sodium;2-ethylhexanoate Chemical compound [Na+].CCCCC(CC)C([O-])=O VYPDUQYOLCLEGS-UHFFFAOYSA-M 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- YTQQIHUQLOZOJI-UHFFFAOYSA-N 2,3-dihydro-1,2-thiazole Chemical compound C1NSC=C1 YTQQIHUQLOZOJI-UHFFFAOYSA-N 0.000 claims description 3
- XHDRIAFCYSITRY-UHFFFAOYSA-N 6,7-dihydroxy-4-oxochromene-3-carbonyl chloride Chemical compound O1C=C(C(Cl)=O)C(=O)C2=C1C=C(O)C(O)=C2 XHDRIAFCYSITRY-UHFFFAOYSA-N 0.000 claims description 3
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 239000012442 inert solvent Substances 0.000 claims description 3
- GRWIABMEEKERFV-UHFFFAOYSA-N methanol;oxolane Chemical compound OC.C1CCOC1 GRWIABMEEKERFV-UHFFFAOYSA-N 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical group C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 claims description 2
- MBIZXFATKUQOOA-UHFFFAOYSA-N 1,3,4-thiadiazole Chemical group C1=NN=CS1 MBIZXFATKUQOOA-UHFFFAOYSA-N 0.000 claims description 2
- WAZOHTWJSBCXJV-UHFFFAOYSA-N 2-(2-sulfanylidene-3h-1,3,4-oxadiazol-5-yl)acetic acid Chemical compound OC(=O)CC1=NN=C(S)O1 WAZOHTWJSBCXJV-UHFFFAOYSA-N 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 4
- 230000036647 reaction Effects 0.000 claims 2
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims 1
- 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 claims 1
- 125000003831 tetrazolyl group Chemical group 0.000 claims 1
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 claims 1
- 241000894006 Bacteria Species 0.000 abstract description 4
- 241000192125 Firmicutes Species 0.000 abstract description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 86
- 239000000243 solution Substances 0.000 description 72
- 239000000047 product Substances 0.000 description 52
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 49
- 239000000203 mixture Substances 0.000 description 48
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 46
- 238000000862 absorption spectrum Methods 0.000 description 46
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 45
- 229940035423 ethyl ether Drugs 0.000 description 42
- 238000001914 filtration Methods 0.000 description 42
- 238000002844 melting Methods 0.000 description 42
- 230000008018 melting Effects 0.000 description 42
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 40
- 238000003756 stirring Methods 0.000 description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
- 239000002244 precipitate Substances 0.000 description 34
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 238000000354 decomposition reaction Methods 0.000 description 32
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 31
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 28
- 238000000921 elemental analysis Methods 0.000 description 24
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- 239000000725 suspension Substances 0.000 description 17
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
- 235000019341 magnesium sulphate Nutrition 0.000 description 15
- 238000004821 distillation Methods 0.000 description 14
- 239000002253 acid Substances 0.000 description 11
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 10
- 239000012153 distilled water Substances 0.000 description 10
- 239000011780 sodium chloride Substances 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 239000012141 concentrate Substances 0.000 description 9
- 235000008504 concentrate Nutrition 0.000 description 9
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
- 239000001913 cellulose Substances 0.000 description 6
- 229920002678 cellulose Polymers 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 229920001817 Agar Polymers 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000008272 agar Substances 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
- 159000000007 calcium salts Chemical class 0.000 description 4
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 4
- 239000008116 calcium stearate Substances 0.000 description 4
- 235000013539 calcium stearate Nutrition 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- JILPJDVXYVTZDQ-UHFFFAOYSA-N lithium methoxide Chemical compound [Li+].[O-]C JILPJDVXYVTZDQ-UHFFFAOYSA-N 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 238000001228 spectrum Methods 0.000 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 description 3
- SPBUACVAGUKSKS-UHFFFAOYSA-N 6,7-diacetyloxy-4-oxochromene-3-carboxylic acid Chemical compound O1C=C(C(O)=O)C(=O)C2=C1C=C(OC(=O)C)C(OC(C)=O)=C2 SPBUACVAGUKSKS-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical class 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
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 230000008023 solidification Effects 0.000 description 3
- 238000007711 solidification Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 238000001665 trituration Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- LCLYFKCQTYLFNG-UHFFFAOYSA-N (3-carbonochloridoyl-6-ethoxycarbonyloxy-4-oxochromen-7-yl) ethyl carbonate Chemical compound O1C=C(C(Cl)=O)C(=O)C2=C1C=C(OC(=O)OCC)C(OC(=O)OCC)=C2 LCLYFKCQTYLFNG-UHFFFAOYSA-N 0.000 description 2
- DQXGRWUCUWYOSX-UHFFFAOYSA-N 6,7-bis(ethoxycarbonyloxy)-4-oxochromene-3-carboxylic acid Chemical compound O1C=C(C(O)=O)C(=O)C2=C1C=C(OC(=O)OCC)C(OC(=O)OCC)=C2 DQXGRWUCUWYOSX-UHFFFAOYSA-N 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 239000003810 Jones reagent Substances 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N alpha-methyl toluene Natural products CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 229940105329 carboxymethylcellulose Drugs 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 2
- CHDFNIZLAAFFPX-UHFFFAOYSA-N ethoxyethane;oxolane Chemical compound CCOCC.C1CCOC1 CHDFNIZLAAFFPX-UHFFFAOYSA-N 0.000 description 2
- SHZIWNPUGXLXDT-UHFFFAOYSA-N ethyl hexanoate Chemical compound CCCCCC(=O)OCC SHZIWNPUGXLXDT-UHFFFAOYSA-N 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachlorophenol Chemical compound OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 2
- 239000008057 potassium phosphate buffer Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 239000000196 tragacanth Substances 0.000 description 2
- 235000010487 tragacanth Nutrition 0.000 description 2
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- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 1
- 229960002218 sodium chlorite Drugs 0.000 description 1
- YFGAFXCSLUUJRG-WCCKRBBISA-M sodium;(2s)-2-amino-5-(diaminomethylideneamino)pentanoate Chemical compound [Na+].[O-]C(=O)[C@@H](N)CCCN=C(N)N YFGAFXCSLUUJRG-WCCKRBBISA-M 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 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
- IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical compound CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000001974 tryptic soy broth Substances 0.000 description 1
- 108010050327 trypticase-soy broth Proteins 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
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
-
- 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 (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP26,112/80 | 1980-03-04 | ||
| JP2611280A JPS56122384A (en) | 1980-03-04 | 1980-03-04 | 7alpha-methoxycephalosporin derivative, its preparation and antifungal agent comprising it |
| JP92,199/80 | 1980-07-08 | ||
| JP9219980A JPS5718689A (en) | 1980-07-08 | 1980-07-08 | 7alpha-methoxycephem derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1165759A true CA1165759A (en) | 1984-04-17 |
Family
ID=26363848
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000367539A Expired CA1165759A (en) | 1980-03-04 | 1980-12-24 | 7.alpha.-METHOXYCEPHALOSPORIN DERIVATIVES, PROCESS FOR THE PREPARATION THEREOF AND ANTIBACTERIAL DRUGS CONTAINING THE SAME |
Country Status (17)
| Country | Link |
|---|---|
| US (2) | US4344944A (enExample) |
| KR (1) | KR840002162B1 (enExample) |
| AT (1) | AT373895B (enExample) |
| AU (1) | AU540042B2 (enExample) |
| CA (1) | CA1165759A (enExample) |
| CH (1) | CH643850A5 (enExample) |
| DE (1) | DE3048657A1 (enExample) |
| DK (1) | DK548380A (enExample) |
| ES (2) | ES498145A0 (enExample) |
| FR (1) | FR2477548A1 (enExample) |
| GB (1) | GB2070589B (enExample) |
| HU (1) | HU183276B (enExample) |
| IT (1) | IT8026965A0 (enExample) |
| NL (1) | NL8007011A (enExample) |
| PH (1) | PH17794A (enExample) |
| SE (1) | SE8009049L (enExample) |
| SU (3) | SU1095879A3 (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5855491A (ja) * | 1981-09-29 | 1983-04-01 | Eisai Co Ltd | ３−カルバモイルオキシメチルセフエム誘導体およびその製造法 |
| US4546176A (en) * | 1982-12-14 | 1985-10-08 | Eisai Co., Ltd. | 7-Carboxymethoxyphenylacetamido-3-cephem derivatives and antibacterial preparations containing the same |
| AU2002334987A1 (en) * | 2001-10-15 | 2003-04-28 | The Regents Of The University Of Michigan | Systems and methods for the generation of crystalline polymorphs |
| US20070036950A1 (en) * | 2005-08-15 | 2007-02-15 | Royal Brush Manufacturing, Inc. | Dry transfer lettering with separable units |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4165429A (en) * | 1976-06-28 | 1979-08-21 | Yamanouchi Pharmaceutical Co., Ltd. | 7α-METHOXY-CEPHALOSPORANIC ACID DERIVATIVES |
| US4150224A (en) * | 1977-10-04 | 1979-04-17 | Yeda Research And Development Co., Ltd. | 7[[(1-Pyrrollyl)7 acetyl]amino]cephalosporin derivatives |
| US4124762A (en) * | 1977-11-07 | 1978-11-07 | Yeda Research And Development Co., Ltd. | 7-[(Pyridylthiomethyl)phenyl]acetamido-cephalosporin derivatives |
| JPS565487A (en) * | 1979-06-26 | 1981-01-20 | Eisai Co Ltd | Cephalosporin compound, its preparation, and antimicrobial comprising it |
-
1980
- 1980-12-22 DK DK548380A patent/DK548380A/da unknown
- 1980-12-22 SE SE8009049A patent/SE8009049L/xx not_active Application Discontinuation
- 1980-12-23 AT AT0630780A patent/AT373895B/de not_active IP Right Cessation
- 1980-12-23 GB GB8041201A patent/GB2070589B/en not_active Expired
- 1980-12-23 NL NL8007011A patent/NL8007011A/nl not_active Application Discontinuation
- 1980-12-23 DE DE19803048657 patent/DE3048657A1/de not_active Withdrawn
- 1980-12-23 HU HU803106A patent/HU183276B/hu unknown
- 1980-12-24 FR FR8027482A patent/FR2477548A1/fr active Granted
- 1980-12-24 IT IT8026965A patent/IT8026965A0/it unknown
- 1980-12-24 AU AU65830/80A patent/AU540042B2/en not_active Ceased
- 1980-12-24 CA CA000367539A patent/CA1165759A/en not_active Expired
- 1980-12-24 ES ES498145A patent/ES498145A0/es active Granted
- 1980-12-24 CH CH959380A patent/CH643850A5/de not_active IP Right Cessation
- 1980-12-26 KR KR1019800004944A patent/KR840002162B1/ko not_active Expired
- 1980-12-29 US US06/220,723 patent/US4344944A/en not_active Expired - Fee Related
-
1981
- 1981-01-01 PH PH25066A patent/PH17794A/en unknown
- 1981-01-07 SU SU813226153A patent/SU1095879A3/ru active
- 1981-05-28 SU SU813288703A patent/SU1130569A1/ru active
-
1982
- 1982-01-14 ES ES508723A patent/ES8300773A1/es not_active Expired
- 1982-02-18 US US06/349,983 patent/US4415567A/en not_active Expired - Fee Related
- 1982-05-17 SU SU823436637A patent/SU1105117A3/ru active
Also Published As
| Publication number | Publication date |
|---|---|
| DK548380A (da) | 1981-09-05 |
| ES8205809A1 (es) | 1982-06-16 |
| SU1105117A3 (ru) | 1984-07-23 |
| HU183276B (en) | 1984-04-28 |
| IT8026965A0 (it) | 1980-12-24 |
| GB2070589B (en) | 1984-06-06 |
| FR2477548A1 (fr) | 1981-09-11 |
| AU540042B2 (en) | 1984-11-01 |
| DE3048657A1 (de) | 1981-10-01 |
| SU1095879A3 (ru) | 1984-05-30 |
| CH643850A5 (de) | 1984-06-29 |
| ES508723A0 (es) | 1982-11-01 |
| SE8009049L (sv) | 1981-09-05 |
| ES498145A0 (es) | 1982-06-16 |
| FR2477548B1 (enExample) | 1983-06-10 |
| NL8007011A (nl) | 1981-10-01 |
| SU1130569A1 (ru) | 1984-12-23 |
| ES8300773A1 (es) | 1982-11-01 |
| AT373895B (de) | 1984-02-27 |
| PH17794A (en) | 1984-12-13 |
| AU6583080A (en) | 1981-09-10 |
| ATA630780A (de) | 1983-07-15 |
| KR840002162B1 (ko) | 1984-11-24 |
| KR830004316A (ko) | 1983-07-09 |
| US4344944A (en) | 1982-08-17 |
| GB2070589A (en) | 1981-09-09 |
| US4415567A (en) | 1983-11-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |