CA1129408A - Cephalosporine - Google Patents

Cephalosporine

Info

Publication number: CA1129408A
Authority: CA; Canada
Prior art keywords: formula; ceph; group; oxyimino; carboxylate
Prior art date: 1978-05-26
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

Application number

CA328,416A

Other languages

English (en)

Inventor

Barry E. Ayres

David G.H. Livermore

Cynthia H. O'callaghan

Christopher E. Newall

Niall G. Weir

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Glaxo Group Ltd

Original Assignee

Glaxo Group Ltd

Priority date (The priority date 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 date listed.)

1978-05-26

Filing date

1979-05-25

Publication date

1982-08-10

1978-05-26 Priority claimed from GB23041/78A external-priority patent/GB1604723A/en

1978-05-30 Priority claimed from GB24042/78A external-priority patent/GB1586846A/en

1979-05-25 Application filed by Glaxo Group Ltd filed Critical Glaxo Group Ltd

1982-08-10 Application granted granted Critical

1982-08-10 Publication of CA1129408A publication Critical patent/CA1129408A/fr

Status Expired legal-status Critical Current

Links

229940124587 cephalosporin Drugs 0.000 title claims abstract description 26
229930186147 Cephalosporin Natural products 0.000 title claims abstract description 25
150000001780 cephalosporins Chemical class 0.000 title claims abstract description 21
239000003242 anti bacterial agent Substances 0.000 title claims abstract description 20
229940088710 antibiotic agent Drugs 0.000 title claims abstract description 18
150000001875 compounds Chemical class 0.000 claims abstract description 146
-1 1-methylpyridinium-4-yl Chemical group 0.000 claims abstract description 75
238000002360 preparation method Methods 0.000 claims abstract description 44
150000003839 salts Chemical class 0.000 claims abstract description 42
238000000034 method Methods 0.000 claims abstract description 39
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims abstract description 29
150000002148 esters Chemical class 0.000 claims abstract description 26
231100000252 nontoxic Toxicity 0.000 claims abstract description 26
230000003000 nontoxic effect Effects 0.000 claims abstract description 26
230000003115 biocidal effect Effects 0.000 claims abstract description 23
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 18
229910052799 carbon Inorganic materials 0.000 claims abstract description 14
239000005864 Sulphur Substances 0.000 claims abstract description 12
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 12
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 10
229910052705 radium Inorganic materials 0.000 claims abstract description 10
229910052701 rubidium Inorganic materials 0.000 claims abstract description 10
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract 3
239000002253 acid Substances 0.000 claims description 48
238000006243 chemical reaction Methods 0.000 claims description 33
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 32
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 24
230000000903 blocking effect Effects 0.000 claims description 22
239000007858 starting material Substances 0.000 claims description 16
239000012038 nucleophile Substances 0.000 claims description 13
239000003795 chemical substances by application Substances 0.000 claims description 12
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 10
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
125000001424 substituent group Chemical group 0.000 claims description 10
AXSKLZVLVONUIC-UHFFFAOYSA-N 1-methylpyridine-4-thione Chemical compound CN1C=CC(=S)C=C1 AXSKLZVLVONUIC-UHFFFAOYSA-N 0.000 claims description 9
239000002168 alkylating agent Substances 0.000 claims description 9
229940100198 alkylating agent Drugs 0.000 claims description 9
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 8
235000009518 sodium iodide Nutrition 0.000 claims description 8
125000000623 heterocyclic group Chemical group 0.000 claims description 7
125000004076 pyridyl group Chemical group 0.000 claims description 7
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical class [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 6
150000004820 halides Chemical class 0.000 claims description 6
125000005843 halogen group Chemical group 0.000 claims description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
SXBDXXFTJVHSAF-ZCFIWIBFSA-N (6r)-5-thia-1-azabicyclo[4.2.0]oct-3-en-8-one Chemical compound S1C=CCN2C(=O)C[C@H]21 SXBDXXFTJVHSAF-ZCFIWIBFSA-N 0.000 claims description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
125000004423 acyloxy group Chemical group 0.000 claims description 4
125000002883 imidazolyl group Chemical group 0.000 claims description 4
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 4
125000003226 pyrazolyl group Chemical group 0.000 claims description 4
125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
125000003277 amino group Chemical group 0.000 claims description 3
150000001450 anions Chemical class 0.000 claims description 3
239000001257 hydrogen Substances 0.000 claims description 3
229910052739 hydrogen Inorganic materials 0.000 claims description 3
230000007935 neutral effect Effects 0.000 claims description 3
JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 claims description 3
PQBAWAQIRZIWIV-UHFFFAOYSA-N N-methylpyridinium Chemical compound C[N+]1=CC=CC=C1 PQBAWAQIRZIWIV-UHFFFAOYSA-N 0.000 claims description 2
239000000126 substance Substances 0.000 claims description 2
XOZLFQBXKQOGMD-FEVILBRWSA-N (6r,7r)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-(1-carboxycyclobutyl)oxyiminoacetyl]amino]-3-[(1-methylpyridin-1-ium-4-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1=C[N+](C)=CC=C1SCC1=C(C([O-])=O)N2C(=O)[C@@H](NC(=O)C(=N/OC3(CCC3)C(O)=O)\C=3N=C(N)SC=3)[C@H]2SC1 XOZLFQBXKQOGMD-FEVILBRWSA-N 0.000 claims 4
239000012022 methylating agents‎ Substances 0.000 claims 3
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 2
JLAAGXGGKQWWBG-YBNQUCTASA-M [Br-].N[C@H]1[C@@H]2N(C(=C(CS2)CSC2=CC=[N+](C=C2)C)C(=O)OC(C2=CC=CC=C2)C2=CC=CC=C2)C1=O Chemical compound [Br-].N[C@H]1[C@@H]2N(C(=C(CS2)CSC2=CC=[N+](C=C2)C)C(=O)OC(C2=CC=CC=C2)C2=CC=CC=C2)C1=O JLAAGXGGKQWWBG-YBNQUCTASA-M 0.000 claims 2
239000007864 aqueous solution Substances 0.000 claims 2
SNTBRKHKMPCPPU-VHSHMJAOSA-N (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(1-carboxycyclobutyl)oxyiminoacetyl]amino]-8-oxo-3-(pyridin-4-ylsulfanylmethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1C(N)=NC(C(=N\OC2(CCC2)C(O)=O)\C(=O)N[C@@H]2C(N3C(=C(CSC=4C=CN=CC=4)CS[C@@H]32)C(O)=O)=O)=C1 SNTBRKHKMPCPPU-VHSHMJAOSA-N 0.000 claims 1
YWJLSGRPSYHXGF-LGAWNBMASA-N (6r,7r)-3-(acetyloxymethyl)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-(2-carboxypropan-2-yloxyimino)acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C(O)=O)C(=O)C(=N/OC(C)(C)C(O)=O)\C1=CSC(N)=N1 YWJLSGRPSYHXGF-LGAWNBMASA-N 0.000 claims 1
HMZMTHSQPIBOOC-QSRJMCJDSA-N BrCC=1CS[C@H]2N(C=1C(=O)OC(C1=CC=CC=C1)C1=CC=CC=C1)C([C@H]2NC(\C(\C=1N=C(SC=1)NC(C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1)=N/OC1(CCC1)C(=O)OC(C)(C)C)=O)=O Chemical compound BrCC=1CS[C@H]2N(C=1C(=O)OC(C1=CC=CC=C1)C1=CC=CC=C1)C([C@H]2NC(\C(\C=1N=C(SC=1)NC(C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1)=N/OC1(CCC1)C(=O)OC(C)(C)C)=O)=O HMZMTHSQPIBOOC-QSRJMCJDSA-N 0.000 claims 1
CMVYMHYBKKPWMW-IZXJIOGHSA-M C(C)(=O)OCC=1CS[C@H]2N(C=1C(=O)[O-])C([C@H]2NC(\C(=N/OC1(CCC1)C(=O)O)\C=1N=C(SC=1)N)=O)=O.[Na+] Chemical compound C(C)(=O)OCC=1CS[C@H]2N(C=1C(=O)[O-])C([C@H]2NC(\C(=N/OC1(CCC1)C(=O)O)\C=1N=C(SC=1)N)=O)=O.[Na+] CMVYMHYBKKPWMW-IZXJIOGHSA-M 0.000 claims 1
DIQDHIOKDQJJOG-KVEFNJFISA-N C(C)(C)(C)OC(=O)C(C)(C)O\N=C(/C(=O)N[C@H]1[C@@H]2N(C(=C(CS2)CBr)C(=O)OC(C2=CC=CC=C2)C2=CC=CC=C2)C1=O)\C=1N=C(SC=1)NC(C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 Chemical compound C(C)(C)(C)OC(=O)C(C)(C)O\N=C(/C(=O)N[C@H]1[C@@H]2N(C(=C(CS2)CBr)C(=O)OC(C2=CC=CC=C2)C2=CC=CC=C2)C1=O)\C=1N=C(SC=1)NC(C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 DIQDHIOKDQJJOG-KVEFNJFISA-N 0.000 claims 1
RAXXELZNTBOGNW-UHFFFAOYSA-O Imidazolium Chemical compound C1=C[NH+]=CN1 RAXXELZNTBOGNW-UHFFFAOYSA-O 0.000 claims 1
WTKZEGDFNFYCGP-UHFFFAOYSA-O Pyrazolium Chemical compound C1=CN[NH+]=C1 WTKZEGDFNFYCGP-UHFFFAOYSA-O 0.000 claims 1
JUQQTDBBACSOMR-RWFDSMMDSA-M [Na+].NC=1SC=C(N=1)/C(/C(=O)N[C@H]1[C@@H]2N(C(=C(CS2)CSC2=CC=[N+](C=C2)C)C(=O)[O-])C1=O)=N/OC(C)(C)C(=O)[O-] Chemical compound [Na+].NC=1SC=C(N=1)/C(/C(=O)N[C@H]1[C@@H]2N(C(=C(CS2)CSC2=CC=[N+](C=C2)C)C(=O)[O-])C1=O)=N/OC(C)(C)C(=O)[O-] JUQQTDBBACSOMR-RWFDSMMDSA-M 0.000 claims 1
CZPWVGJYEJSRLH-UHFFFAOYSA-O hydron;pyrimidine Chemical compound C1=CN=C[NH+]=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-O 0.000 claims 1
230000001035 methylating effect Effects 0.000 claims 1
230000011987 methylation Effects 0.000 claims 1
238000007069 methylation reaction Methods 0.000 claims 1
GWNVGKQZNVUCRS-QYVLQNAGSA-N tert-butyl 2-[(z)-[2-chloro-2-oxo-1-[2-(tritylamino)-1,3-thiazol-4-yl]ethylidene]amino]oxy-2-methylpropanoate Chemical compound CC(C)(C)OC(=O)C(C)(C)O\N=C(/C(Cl)=O)C1=CSC(NC(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 GWNVGKQZNVUCRS-QYVLQNAGSA-N 0.000 claims 1
239000000203 mixture Substances 0.000 abstract description 68
230000000694 effects Effects 0.000 abstract description 13
125000002373 5 membered heterocyclic group Chemical group 0.000 abstract description 4
125000004070 6 membered heterocyclic group Chemical group 0.000 abstract description 4
230000000844 anti-bacterial effect Effects 0.000 abstract description 4
241000589516 Pseudomonas Species 0.000 abstract description 3
230000001225 therapeutic effect Effects 0.000 abstract description 3
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 112
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 96
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 79
239000000243 solution Substances 0.000 description 67
239000000047 product Substances 0.000 description 64
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 63
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
239000007787 solid Substances 0.000 description 43
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 41
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 26
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 25
150000007513 acids Chemical class 0.000 description 23
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 18
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
239000002585 base Substances 0.000 description 16
239000006260 foam Substances 0.000 description 15
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 15
229910000030 sodium bicarbonate Inorganic materials 0.000 description 13
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
239000000872 buffer Substances 0.000 description 12
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
239000000843 powder Substances 0.000 description 12
235000017557 sodium bicarbonate Nutrition 0.000 description 12
239000000460 chlorine Substances 0.000 description 11
239000002244 precipitate Substances 0.000 description 11
229960001407 sodium bicarbonate Drugs 0.000 description 11
239000010410 layer Substances 0.000 description 10
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
238000005917 acylation reaction Methods 0.000 description 9
238000006073 displacement reaction Methods 0.000 description 9
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 9
125000004055 thiomethyl group Chemical class [H]SC([H])([H])* 0.000 description 9
241000282414 Homo sapiens Species 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
229960000583 acetic acid Drugs 0.000 description 8
125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 8
238000003756 stirring Methods 0.000 description 8
239000000725 suspension Substances 0.000 description 8
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 7
125000000217 alkyl group Chemical group 0.000 description 7
239000012044 organic layer Substances 0.000 description 7
229920005989 resin Polymers 0.000 description 7
239000011347 resin Substances 0.000 description 7
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 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
230000010933 acylation Effects 0.000 description 6
229920001429 chelating resin Polymers 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
235000019253 formic acid Nutrition 0.000 description 6
230000000269 nucleophilic effect Effects 0.000 description 6
239000003960 organic solvent Substances 0.000 description 6
229910000027 potassium carbonate Inorganic materials 0.000 description 6
HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 6
239000004296 sodium metabisulphite Substances 0.000 description 6
235000010262 sodium metabisulphite Nutrition 0.000 description 6
239000002904 solvent Substances 0.000 description 6
125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 description 6
FZEVMBJWXHDLDB-ZCFIWIBFSA-N (6r)-5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical compound S1CC=CN2C(=O)C[C@H]21 FZEVMBJWXHDLDB-ZCFIWIBFSA-N 0.000 description 5
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 5
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
150000008064 anhydrides Chemical class 0.000 description 5
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
238000001704 evaporation Methods 0.000 description 5
230000008020 evaporation Effects 0.000 description 5
239000000284 extract Substances 0.000 description 5
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 4
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 4
239000012346 acetyl chloride Substances 0.000 description 4
150000001408 amides Chemical class 0.000 description 4
229910052794 bromium Inorganic materials 0.000 description 4
DIKBFYAXUHHXCS-UHFFFAOYSA-N bromoform Chemical compound BrC(Br)Br DIKBFYAXUHHXCS-UHFFFAOYSA-N 0.000 description 4
229910052801 chlorine Inorganic materials 0.000 description 4
238000001816 cooling Methods 0.000 description 4
PWAPCRSSMCLZHG-UHFFFAOYSA-N cyclopentylidene Chemical group [C]1CCCC1 PWAPCRSSMCLZHG-UHFFFAOYSA-N 0.000 description 4
229960001760 dimethyl sulfoxide Drugs 0.000 description 4
238000006266 etherification reaction Methods 0.000 description 4
238000001914 filtration Methods 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
239000012429 reaction media Substances 0.000 description 4
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 3
101150041968 CDC13 gene Proteins 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
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JWEQRJSCTFBRSI-PCLIKHOPSA-N rboxylate Chemical compound COC(=O)C1C(N2C3=O)C4=CC=CC=C4OC1(C)N=C2S\C3=C\C(C=1)=CC=C(OC)C=1COC1=CC=CC=C1C JWEQRJSCTFBRSI-PCLIKHOPSA-N 0.000 description 1
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239000012312 sodium hydride Substances 0.000 description 1
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235000010288 sodium nitrite Nutrition 0.000 description 1
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IGVNJALYNQVQIT-UHFFFAOYSA-N tert-butyl 2-bromo-2-methylpropanoate Chemical compound CC(C)(C)OC(=O)C(C)(C)Br IGVNJALYNQVQIT-UHFFFAOYSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
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238000002560 therapeutic procedure Methods 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
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125000003396 thiol group Chemical group [H]S* 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
125000005490 tosylate group Chemical group 0.000 description 1
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125000001425 triazolyl group Chemical group 0.000 description 1
125000001874 trioxidanyl group Chemical group [*]OOO[H] 0.000 description 1
JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 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
238000005866 tritylation reaction Methods 0.000 description 1
208000019206 urinary tract infection Diseases 0.000 description 1

Landscapes

Cephalosporin Compounds (AREA)

CA328,416A 1978-05-26 1979-05-25 Cephalosporine Expired CA1129408A (fr)

Applications Claiming Priority (8)

Application Number	Priority Date	Filing Date	Title
GB23041/78		1978-05-26
GB24042/78		1978-05-26
GB23041/78A GB1604723A (en)	1978-05-26	1978-05-26	7-(2-aminothiazol-4-yl)-2-oxyimino-acetamido)-cephem derivatives
GB24042/78A GB1586846A (en)	1977-06-30	1978-05-30	Signal analysis arrangement for a communications transmission system
GB42166/78		1978-10-27
GB7842196		1978-10-27
GB7842166		1978-10-27
GB42196/78		1978-10-27

Publications (1)

Publication Number	Publication Date
CA1129408A true CA1129408A (fr)	1982-08-10

Family

ID=27448576

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA328,416A Expired CA1129408A (fr)	1978-05-26	1979-05-25	Cephalosporine

Country Status (1)

Country	Link
CA (1)	CA1129408A (fr)

1979
- 1979-05-25 CA CA328,416A patent/CA1129408A/fr not_active Expired

Legal Events

Date	Code	Title	Description
1999-08-10	MKEX	Expiry

Publication	Publication Date	Title
US4258041A (en)	1981-03-24	(6R,7R)-7-[(Z)-2-(2-Aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-(1-pyridiniummethyl)-ceph-3-em-4-carboxylate and salts thereof
US4621081A (en)	1986-11-04	Cephalosporin antibiotics
CA1132538A (fr)	1982-09-28	Cephalosporine
US4464368A (en)	1984-08-07	Cephalosporin antibiotics
CA1130280A (fr)	1982-08-24	Cephalosporines
US4315005A (en)	1982-02-09	Cephalosporin antibiotics
US4504477A (en)	1985-03-12	Cephalosporin antibiotics
US4427675A (en)	1984-01-24	Cephalosporin antibiotics
CA1131618A (fr)	1982-09-14	Composes de cephalosporine
KR830001130B1 (ko)	1983-06-14	세팔로스포린 항생제의 제조방법
CA1129408A (fr)	1982-08-10	Cephalosporine
GB2046261A (en)	1980-11-12	Cephalosporin antibiotics
US4560683A (en)	1985-12-24	Cephalosporin antibiotics
GB2027691A (en)	1980-02-27	Cephalosporin Antibiotics
GB1604724A (en)	1981-12-16	7-(2-aminothiazol-4-yl)-2-oxymino-acedamido)-cephem derivatives
GB2036738A (en)	1980-07-02	Cephalosporin antibiotics
GB2037281A (en)	1980-07-09	7-( alpha -(2-amino.4-thiazolyl)- alpha - hydroximino-acetamido)- cephalosporins
KR830001592B1 (ko)	1983-08-16	세팔로스포린 항생제의 제조방법
CA1122973A (fr)	1982-05-04	Cephalosporines
IE49171B1 (en)	1985-08-21	Cephalosporin antibiotics
IE49174B1 (en)	1985-08-21	Cephalosporin antibiotics
EP0095329A2 (fr)	1983-11-30	Céphalosporines antibiotiques
GB2062624A (en)	1981-05-28	Cephalosporin Antibiotics
GB2123415A (en)	1984-02-01	Cephalosporin antibiotics
GB2029824A (en)	1980-03-26	7-( alpha -oximino- alpha -2-amino-4-thiazolyl-acetamido)-cephens