DE2460537C2 - 7-β-Acylamido-3-em-4-carbonsäure-Antibiotika - Google Patents
7-β-Acylamido-3-em-4-carbonsäure-AntibiotikaInfo
- Publication number
- DE2460537C2 DE2460537C2 DE2460537A DE2460537A DE2460537C2 DE 2460537 C2 DE2460537 C2 DE 2460537C2 DE 2460537 A DE2460537 A DE 2460537A DE 2460537 A DE2460537 A DE 2460537A DE 2460537 C2 DE2460537 C2 DE 2460537C2
- Authority
- DE
- Germany
- Prior art keywords
- udf54
- udf53
- acid
- fur
- compound
- 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
- 239000003242 anti bacterial agent Substances 0.000 title claims description 14
- 229940088710 antibiotic agent Drugs 0.000 title claims description 10
- 150000001875 compounds Chemical class 0.000 claims description 85
- 239000000203 mixture Substances 0.000 claims description 56
- -1 sulpho group Chemical group 0.000 claims description 51
- 238000000034 method Methods 0.000 claims description 43
- 239000002253 acid Substances 0.000 claims description 36
- 150000003839 salts Chemical class 0.000 claims description 25
- 238000002360 preparation method Methods 0.000 claims description 20
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 18
- 150000002148 esters Chemical class 0.000 claims description 15
- 230000003115 biocidal effect Effects 0.000 claims description 14
- 239000012038 nucleophile Substances 0.000 claims description 14
- 230000008569 process Effects 0.000 claims description 13
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 10
- 150000003254 radicals Chemical class 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 9
- 238000005917 acylation reaction Methods 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 231100000252 nontoxic Toxicity 0.000 claims description 7
- 230000003000 nontoxic effect Effects 0.000 claims description 7
- 230000010933 acylation Effects 0.000 claims description 6
- NYBWUHOMYZZKOR-UHFFFAOYSA-N tes-adt Chemical class C1=C2C(C#C[Si](CC)(CC)CC)=C(C=C3C(SC=C3)=C3)C3=C(C#C[Si](CC)(CC)CC)C2=CC2=C1SC=C2 NYBWUHOMYZZKOR-UHFFFAOYSA-N 0.000 claims description 6
- 230000000903 blocking effect Effects 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- NGBCKGUDDFQTSY-MLGOLLRUSA-N (6r,7r)-3-(carbamoyloxymethyl)-7-[[2-(1-carboxycyclobutyl)oxyimino-2-(furan-2-yl)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)N)C(O)=O)C(=O)C(C=1OC=CC=1)=NOC1(C(O)=O)CCC1 NGBCKGUDDFQTSY-MLGOLLRUSA-N 0.000 claims description 2
- CDVKMCXHXCGWFH-IAQYHMDHSA-N (6r,7r)-3-(carbamoyloxymethyl)-7-[[2-(carboxymethoxyimino)-2-(furan-2-yl)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)N)C(O)=O)C(=O)C(=NOCC(O)=O)C1=CC=CO1 CDVKMCXHXCGWFH-IAQYHMDHSA-N 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 2
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 claims description 2
- 239000012964 benzotriazole Substances 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 1
- 230000021235 carbamoylation Effects 0.000 claims 1
- 125000004093 cyano group Chemical group *C#N 0.000 claims 1
- 230000020176 deacylation Effects 0.000 claims 1
- 238000005947 deacylation reaction Methods 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 101150009274 nhr-1 gene Proteins 0.000 claims 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical group C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- 239000012453 solvate Substances 0.000 claims 1
- 125000003831 tetrazolyl group Chemical group 0.000 claims 1
- 125000001113 thiadiazolyl group Chemical group 0.000 claims 1
- 125000001544 thienyl group Chemical group 0.000 claims 1
- 150000003852 triazoles Chemical class 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 180
- 239000000243 solution Substances 0.000 description 125
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 119
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 115
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 78
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 74
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 55
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 51
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 44
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 44
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 39
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 26
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 26
- 235000017557 sodium bicarbonate Nutrition 0.000 description 26
- 239000000047 product Substances 0.000 description 25
- 239000003208 petroleum Substances 0.000 description 23
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 21
- 239000007787 solid Substances 0.000 description 20
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 17
- 239000010410 layer Substances 0.000 description 17
- 238000003756 stirring Methods 0.000 description 17
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- 229940124587 cephalosporin Drugs 0.000 description 15
- 239000000284 extract Substances 0.000 description 15
- 239000006260 foam Substances 0.000 description 15
- 238000004519 manufacturing process Methods 0.000 description 15
- 150000003952 β-lactams Chemical class 0.000 description 15
- 229930186147 Cephalosporin Natural products 0.000 description 14
- 230000000694 effects Effects 0.000 description 14
- 239000008363 phosphate buffer Substances 0.000 description 14
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 14
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 13
- 239000012044 organic layer Substances 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000012267 brine Substances 0.000 description 12
- DIKBFYAXUHHXCS-UHFFFAOYSA-N bromoform Chemical compound BrC(Br)Br DIKBFYAXUHHXCS-UHFFFAOYSA-N 0.000 description 12
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 12
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 12
- 239000003921 oil Substances 0.000 description 11
- 235000019198 oils Nutrition 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 150000005690 diesters Chemical class 0.000 description 10
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 9
- 235000019441 ethanol Nutrition 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 239000002244 precipitate Substances 0.000 description 9
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
- 241000588769 Proteus <enterobacteria> Species 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 150000001780 cephalosporins Chemical class 0.000 description 8
- 229920005989 resin Polymers 0.000 description 8
- 239000011347 resin Substances 0.000 description 8
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 7
- 239000004793 Polystyrene Substances 0.000 description 7
- 241000589516 Pseudomonas Species 0.000 description 7
- 239000008346 aqueous phase Substances 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- IPZJQDSFZGZEOY-UHFFFAOYSA-N dimethylmethylene Chemical compound C[C]C IPZJQDSFZGZEOY-UHFFFAOYSA-N 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 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 6
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 6
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- 238000001665 trituration Methods 0.000 description 6
- QRNIMLMZOWZXRW-UHFFFAOYSA-N 2-(furan-2-yl)-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]iminoacetic acid Chemical compound CC(C)(C)OC(=O)CON=C(C(O)=O)C1=CC=CO1 QRNIMLMZOWZXRW-UHFFFAOYSA-N 0.000 description 5
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 5
- 239000012346 acetyl chloride Substances 0.000 description 5
- 125000005042 acyloxymethyl group Chemical group 0.000 description 5
- 150000008064 anhydrides Chemical class 0.000 description 5
- 102000006635 beta-lactamase Human genes 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 229920001429 chelating resin Polymers 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- 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 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical compound CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 4
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-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
- 235000011054 acetic acid Nutrition 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 238000006266 etherification reaction Methods 0.000 description 4
- 238000006317 isomerization reaction Methods 0.000 description 4
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 4
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 4
- 229940001584 sodium metabisulfite Drugs 0.000 description 4
- 235000010262 sodium metabisulphite Nutrition 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- JYJSCVFRYQIHJP-CXAGYDPISA-N (6r,7r)-3-(acetyloxymethyl)-7-[[2-(carboxymethoxyimino)-2-(furan-2-yl)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(=NOCC(O)=O)C1=CC=CO1 JYJSCVFRYQIHJP-CXAGYDPISA-N 0.000 description 3
- XXYOXWNGBUSXJC-UHFFFAOYSA-N 2-(furan-2-yl)-2-[2-methyl-1-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]oxyiminoacetic acid Chemical compound CC(C)(C)OC(=O)C(C)(C)ON=C(C(O)=O)C1=CC=CO1 XXYOXWNGBUSXJC-UHFFFAOYSA-N 0.000 description 3
- IXVPCJUAKDVYKX-UHFFFAOYSA-N 2-(furan-2-yl)-2-oxoacetic acid Chemical compound OC(=O)C(=O)C1=CC=CO1 IXVPCJUAKDVYKX-UHFFFAOYSA-N 0.000 description 3
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
- 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 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- AGPSFEBXCMASIE-YETOVSRYSA-N BrCC=1C[S@@]([C@H]2N(C=1C(=O)OC(C1=CC=CC=C1)C1=CC=CC=C1)C([C@H]2NC(C(C=1OC=CC=1)=NOC(C)(C)C(=O)OC(C)(C)C)=O)=O)=O Chemical compound BrCC=1C[S@@]([C@H]2N(C=1C(=O)OC(C1=CC=CC=C1)C1=CC=CC=C1)C([C@H]2NC(C(C=1OC=CC=1)=NOC(C)(C)C(=O)OC(C)(C)C)=O)=O)=O AGPSFEBXCMASIE-YETOVSRYSA-N 0.000 description 3
- 108090000204 Dipeptidase 1 Proteins 0.000 description 3
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 3
- 241000606768 Haemophilus influenzae Species 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 238000007257 deesterification reaction Methods 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 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 3
- 239000012259 ether extract Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 229940047650 haemophilus influenzae Drugs 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
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- 238000004042 decolorization Methods 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 239000011928 denatured alcohol Substances 0.000 description 1
- 239000002027 dichloromethane extract Substances 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- KCIDZIIHRGYJAE-YGFYJFDDSA-L dipotassium;[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] phosphate Chemical class [K+].[K+].OC[C@H]1O[C@H](OP([O-])([O-])=O)[C@H](O)[C@@H](O)[C@H]1O KCIDZIIHRGYJAE-YGFYJFDDSA-L 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- JNQFSQKQGRNFAA-UHFFFAOYSA-N ditert-butyl 2-bromo-2-methylpropanedioate Chemical compound CC(C)(C)OC(=O)C(C)(Br)C(=O)OC(C)(C)C JNQFSQKQGRNFAA-UHFFFAOYSA-N 0.000 description 1
- GBWGGPUIWKWJIT-UHFFFAOYSA-N ditert-butyl 2-methylpropanedioate Chemical compound CC(C)(C)OC(=O)C(C)C(=O)OC(C)(C)C GBWGGPUIWKWJIT-UHFFFAOYSA-N 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000008570 general process Effects 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 125000004993 haloalkoxycarbonyl group Chemical group 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 150000002443 hydroxylamines Chemical class 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 1
- 229940006461 iodide ion Drugs 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- HQOQSFITXGQQDM-SSDOTTSWSA-N methyl (6R)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound COC(=O)C1=CCS[C@@H]2CC(=O)N12 HQOQSFITXGQQDM-SSDOTTSWSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- JCXVPCYMKJTPEE-UHFFFAOYSA-N methyl n-hydroxyethanimidate Chemical compound COC(C)=NO JCXVPCYMKJTPEE-UHFFFAOYSA-N 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- HSZCJVZRHXPCIA-UHFFFAOYSA-N n-benzyl-n-ethylaniline Chemical compound C=1C=CC=CC=1N(CC)CC1=CC=CC=C1 HSZCJVZRHXPCIA-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 229910017464 nitrogen compound Inorganic materials 0.000 description 1
- 150000002830 nitrogen compounds Chemical class 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000005646 oximino group Chemical group 0.000 description 1
- 150000002924 oxiranes Chemical class 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 238000004816 paper chromatography Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920005990 polystyrene resin Polymers 0.000 description 1
- 229920003053 polystyrene-divinylbenzene Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 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
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-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
- 229920001592 potato starch Polymers 0.000 description 1
- 230000002335 preservative effect Effects 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
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical class CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical group C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 235000020374 simple syrup Nutrition 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- KAYQFHYRBAPSJG-KEZWHQCISA-M sodium (6R,7R)-3-(carbamoyloxymethyl)-7-[[2-(furan-2-yl)-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]iminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C(N)(=O)OCC=1CS[C@H]2N(C=1C(=O)[O-])C([C@H]2NC(C(C=1OC=CC=1)=NOCC(=O)OC(C)(C)C)=O)=O.[Na+] KAYQFHYRBAPSJG-KEZWHQCISA-M 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- AAMCVENDCXWDPJ-UHFFFAOYSA-N sulfanyl acetate Chemical class CC(=O)OS AAMCVENDCXWDPJ-UHFFFAOYSA-N 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 125000000542 sulfonic acid group Chemical group 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- SKVHPNQACYIQDC-BXKDBHETSA-N tert-butyl (6r,7r)-3-(acetyloxymethyl)-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S1CC(COC(=O)C)=C(C(=O)OC(C)(C)C)N2C(=O)[C@@H](N)[C@@H]12 SKVHPNQACYIQDC-BXKDBHETSA-N 0.000 description 1
- GWQJIVXXGBOBIN-UHFFFAOYSA-N tert-butyl 1-[[2-chloro-1-(furan-2-yl)-2-oxoethylidene]amino]oxycyclopentane-1-carboxylate Chemical compound C(C)(C)(C)OC(=O)C1(CCCC1)ON=C(C(=O)Cl)C=1OC=CC1 GWQJIVXXGBOBIN-UHFFFAOYSA-N 0.000 description 1
- LEPOFWDYYOBLGW-UHFFFAOYSA-N tert-butyl 1-bromocyclopentane-1-carboxylate Chemical compound CC(C)(C)OC(=O)C1(Br)CCCC1 LEPOFWDYYOBLGW-UHFFFAOYSA-N 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- ZPIHBLASZNAFMU-UHFFFAOYSA-N tert-butyl 2-aminooxy-2-phenylacetate Chemical compound CC(C)(C)OC(=O)C(ON)C1=CC=CC=C1 ZPIHBLASZNAFMU-UHFFFAOYSA-N 0.000 description 1
- QMOSMBHBHVHTSB-UHFFFAOYSA-N tert-butyl 2-bromo-2-phenylacetate Chemical compound CC(C)(C)OC(=O)C(Br)C1=CC=CC=C1 QMOSMBHBHVHTSB-UHFFFAOYSA-N 0.000 description 1
- KUYMVWXKHQSIAS-UHFFFAOYSA-N tert-butyl 2-chloroacetate Chemical compound CC(C)(C)OC(=O)CCl KUYMVWXKHQSIAS-UHFFFAOYSA-N 0.000 description 1
- ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229940040944 tetracyclines Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 150000003628 tricarboxylic acids Chemical class 0.000 description 1
- 150000005691 triesters Chemical class 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000002132 β-lactam antibiotic Substances 0.000 description 1
- 229940124586 β-lactam antibiotics Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB59517/73A GB1496757A (en) | 1973-12-21 | 1973-12-21 | Cephalosporin derivatives |
GB4300574 | 1974-10-03 |
Publications (2)
Publication Number | Publication Date |
---|---|
DE2460537A1 DE2460537A1 (de) | 1975-07-03 |
DE2460537C2 true DE2460537C2 (de) | 1987-01-22 |
Family
ID=26265028
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE2460537A Expired DE2460537C2 (de) | 1973-12-21 | 1974-12-20 | 7-β-Acylamido-3-em-4-carbonsäure-Antibiotika |
Country Status (15)
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3019462A1 (de) * | 1979-05-23 | 1980-12-04 | Rhone Poulenc Ind | Neue 3-vinyl-cephalosporin-derivate und verfahren zu deren herstellung |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4144393A (en) | 1973-12-21 | 1979-03-13 | Glaxo Laboratories Limited | 3-Acetoxymethyl cephalosporins having at position-7 a carboxy substituted α-etherified hydroxyiminoarylacetamido group |
US4144392A (en) | 1973-12-21 | 1979-03-13 | Glaxo Laboratories Limited | Cephalosporins having at position-7 a carboxy substituted α-etherified hydroxyimino-arylacetamido group and at position-3 the residue of a sulphur nucleophile |
GB1555471A (en) * | 1975-06-19 | 1979-11-14 | Glaxo Lab Ltd | 7 carbamoylalkoxyimino acetamido 3 em 4 carboxylic acidsand derivatives thereof |
CA1093549A (en) * | 1976-02-16 | 1981-01-13 | Michael Gregson | Cephalosporin antibiotics |
US4165430A (en) | 1976-03-19 | 1979-08-21 | Glaxo Laboratories Limited | Cephalosporins having a 7-carboxy substituted α-etherified oximinoarylacetamido) group |
US4304770A (en) | 1976-04-12 | 1981-12-08 | Fujisawa Pharmaceutical Co., Ltd. | Syn-isomer of 3,7-disubstituted-3-cephem-4-carboxylic acid compounds and processes for the preparation thereof |
US4278670A (en) * | 1976-07-12 | 1981-07-14 | Smithkline Corporation | 7-Alpha-oxyiminoacylcephalosporins |
US4066762A (en) * | 1976-07-12 | 1978-01-03 | Smithkline Corporation | Derivatives of 7-(2-substituted-2-hydroxyiminoacetamido)-3-(1-substituted tetrazol-5-ylthiomethyl-3-cephem-4-carboxylic acid |
GB1591439A (en) | 1976-10-01 | 1981-06-24 | Glaxo Operations Ltd | 7-syn (oxyimino -acylamido) cephalosporins |
GB1596278A (en) | 1976-11-30 | 1981-08-26 | Glaxo Operations Ltd | 7-(-oxyimino-acetamino)cephalosporin derivatives |
PH17188A (en) | 1977-03-14 | 1984-06-14 | Fujisawa Pharmaceutical Co | New cephem and cepham compounds and their pharmaceutical compositions and method of use |
SE439312B (sv) * | 1977-03-25 | 1985-06-10 | Roussel Uclaf | Sett att framstella nya oximderivat av 3-acetoximetyl-7-aminotiazolylacetamido cefalosporansyra |
IE49100B1 (en) * | 1978-10-27 | 1985-07-24 | Glaxo Group Ltd | Cephalosporin compounds |
FR2552432B2 (fr) * | 1983-09-27 | 1985-10-25 | Roussel Uclaf | Nouvelles oximes derivees de l'acide 2-amino thiazol- 4-yl acetique, procede de preparation |
US20040166434A1 (en) | 2003-02-21 | 2004-08-26 | Dammel Ralph R. | Photoresist composition for deep ultraviolet lithography |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3641021A (en) * | 1969-04-18 | 1972-02-08 | Lilly Co Eli | 3 7-(ring-substituted) cephalosporin compounds |
GB1348985A (en) * | 1970-06-16 | 1974-03-27 | Merck & Co Inc | Esters of cephalosporin compounds |
GB1399086A (en) * | 1971-05-14 | 1975-06-25 | Glaxo Lab Ltd | Cephalosporin compounds |
-
1974
- 1974-12-20 IL IL46302A patent/IL46302A/xx unknown
- 1974-12-20 CH CH1708674A patent/CH617703A5/de not_active IP Right Cessation
- 1974-12-20 HU HU74GA00001174A patent/HU172234B/hu unknown
- 1974-12-20 SE SE7416195A patent/SE7416195L/xx unknown
- 1974-12-20 ES ES433226A patent/ES433226A1/es not_active Expired
- 1974-12-20 JP JP49147519A patent/JPS5844675B2/ja not_active Expired
- 1974-12-20 AT AT1020174A patent/AT344888B/de not_active IP Right Cessation
- 1974-12-20 DE DE2460537A patent/DE2460537C2/de not_active Expired
- 1974-12-20 DK DK674674A patent/DK674674A/da unknown
- 1974-12-20 FI FI3713/74A patent/FI65258C/fi active
- 1974-12-20 LU LU71550A patent/LU71550A1/xx unknown
- 1974-12-20 NL NL7416665A patent/NL7416665A/xx not_active Application Discontinuation
- 1974-12-20 NO NO744621A patent/NO744621L/no unknown
- 1974-12-20 IE IE2639/74A patent/IE42144B1/en unknown
- 1974-12-23 FR FR7442541A patent/FR2255076B1/fr not_active Expired
-
1976
- 1976-09-16 ES ES451604A patent/ES451604A1/es not_active Expired
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3019462A1 (de) * | 1979-05-23 | 1980-12-04 | Rhone Poulenc Ind | Neue 3-vinyl-cephalosporin-derivate und verfahren zu deren herstellung |
Also Published As
Publication number | Publication date |
---|---|
IL46302A (en) | 1978-09-29 |
LU71550A1 (US20030199744A1-20031023-C00003.png) | 1976-04-13 |
AU7673574A (en) | 1976-06-24 |
NL7416665A (nl) | 1975-06-24 |
JPS5844675B2 (ja) | 1983-10-04 |
FR2255076B1 (US20030199744A1-20031023-C00003.png) | 1978-11-10 |
SE7416195L (sv) | 1975-09-22 |
ES433226A1 (es) | 1977-07-01 |
IE42144B1 (en) | 1980-06-18 |
FI371374A (US20030199744A1-20031023-C00003.png) | 1975-06-22 |
IL46302A0 (en) | 1975-03-13 |
ES451604A1 (es) | 1977-12-16 |
HU172234B (hu) | 1978-07-28 |
AT344888B (de) | 1978-08-10 |
CH617703A5 (en) | 1980-06-13 |
FI65258B (fi) | 1983-12-30 |
FR2255076A1 (US20030199744A1-20031023-C00003.png) | 1975-07-18 |
DK674674A (US20030199744A1-20031023-C00003.png) | 1975-09-08 |
DE2460537A1 (de) | 1975-07-03 |
JPS50105689A (US20030199744A1-20031023-C00003.png) | 1975-08-20 |
NO744621L (US20030199744A1-20031023-C00003.png) | 1975-07-21 |
FI65258C (fi) | 1984-04-10 |
IE42144L (en) | 1975-06-21 |
ATA1020174A (de) | 1977-12-15 |
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