CA1041480A - 3-(substituted) carbonylamino cephem derivatives - Google Patents
3-(substituted) carbonylamino cephem derivativesInfo
- Publication number
- CA1041480A CA1041480A CA237,187A CA237187A CA1041480A CA 1041480 A CA1041480 A CA 1041480A CA 237187 A CA237187 A CA 237187A CA 1041480 A CA1041480 A CA 1041480A
- Authority
- CA
- Canada
- Prior art keywords
- cephem
- benzhydryl
- thienylacetamido
- carboxylate
- carboxylic acid
- 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
- -1 carbonylamino cephem Chemical class 0.000 title claims description 221
- 150000001875 compounds Chemical class 0.000 claims abstract description 42
- 150000002148 esters Chemical class 0.000 claims abstract description 23
- 239000000126 substance Substances 0.000 claims abstract description 21
- 238000004519 manufacturing process Methods 0.000 claims abstract description 16
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims description 79
- 238000000034 method Methods 0.000 claims description 45
- 238000006243 chemical reaction Methods 0.000 claims description 41
- 239000002253 acid Substances 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- 239000001257 hydrogen Substances 0.000 claims description 24
- 230000008569 process Effects 0.000 claims description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 19
- 238000010438 heat treatment Methods 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 125000002252 acyl group Chemical group 0.000 claims description 11
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 claims description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 10
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 10
- 150000001732 carboxylic acid derivatives Chemical group 0.000 claims description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- 150000007513 acids Chemical class 0.000 claims description 9
- 125000004185 ester group Chemical group 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 230000002633 protecting effect Effects 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 7
- JKTYGPATCNUWKN-UHFFFAOYSA-N 4-nitrobenzyl alcohol Chemical compound OCC1=CC=C([N+]([O-])=O)C=C1 JKTYGPATCNUWKN-UHFFFAOYSA-N 0.000 claims description 6
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 6
- 150000002431 hydrogen Chemical group 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 231100000252 nontoxic Toxicity 0.000 claims description 5
- 230000003000 nontoxic effect Effects 0.000 claims description 5
- 239000012434 nucleophilic reagent Substances 0.000 claims description 5
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 4
- 239000003054 catalyst Substances 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 230000009467 reduction Effects 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 2
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000004970 halomethyl group Chemical group 0.000 claims description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
- 125000006502 nitrobenzyl group Chemical group 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 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 description 2
- 125000003944 tolyl group Chemical group 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 5
- YPNVJUPWZCUTOD-UHFFFAOYSA-L disodium;2,2-dimethylpropanedioate Chemical compound [Na+].[Na+].[O-]C(=O)C(C)(C)C([O-])=O YPNVJUPWZCUTOD-UHFFFAOYSA-L 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 1
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims 1
- YGRJBPCJUMRFHF-HOINCLMKSA-N dimethyl 2-[[(6r)-2-benzhydryloxycarbonyl-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]carbamoyl]propanedioate Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)NC(=O)C(C(=O)OC)C(=O)OC)C(=O)OC(C=1C=CC=CC=1)C=1C=CC=CC=1)NC(=O)CC1=CC=CS1 YGRJBPCJUMRFHF-HOINCLMKSA-N 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 16
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 abstract description 10
- 229930186147 Cephalosporin Natural products 0.000 abstract description 9
- 229940124587 cephalosporin Drugs 0.000 abstract description 9
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 abstract description 7
- 150000001780 cephalosporins Chemical class 0.000 abstract description 7
- 239000003242 anti bacterial agent Substances 0.000 abstract description 5
- 229940088710 antibiotic agent Drugs 0.000 abstract description 5
- 230000003115 biocidal effect Effects 0.000 abstract description 5
- 125000004414 alkyl thio group Chemical group 0.000 abstract description 4
- 125000004442 acylamino group Chemical group 0.000 abstract description 3
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 abstract description 2
- 125000001261 isocyanato group Chemical group *N=C=O 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 105
- 239000000243 solution Substances 0.000 description 57
- 230000000875 corresponding effect Effects 0.000 description 38
- 229940093499 ethyl acetate Drugs 0.000 description 35
- 235000019439 ethyl acetate Nutrition 0.000 description 35
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- 239000011541 reaction mixture Substances 0.000 description 27
- 238000002360 preparation method Methods 0.000 description 25
- 239000000047 product Substances 0.000 description 25
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 20
- 101150041968 CDC13 gene Proteins 0.000 description 20
- 239000000203 mixture Substances 0.000 description 20
- 150000001782 cephems Chemical class 0.000 description 19
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 18
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 18
- 239000012267 brine Substances 0.000 description 17
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 16
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- 238000001704 evaporation Methods 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- 239000002585 base Substances 0.000 description 11
- 230000008020 evaporation Effects 0.000 description 11
- 239000012948 isocyanate Substances 0.000 description 11
- 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 10
- 125000006239 protecting group Chemical group 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- 229940086542 triethylamine Drugs 0.000 description 10
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- 229910052708 sodium Inorganic materials 0.000 description 9
- 235000017557 sodium bicarbonate Nutrition 0.000 description 9
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- 239000003960 organic solvent Substances 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- ZOOQYKLSRFWNMF-NQPNHJOESA-N (6R)-4-isocyanato-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C(=O)=NC1S[C@H]2N(C(=C1)C(=O)O)C(C2)=O ZOOQYKLSRFWNMF-NQPNHJOESA-N 0.000 description 7
- 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 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 7
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- 150000002513 isocyanates Chemical class 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 229940022663 acetate Drugs 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 238000005886 esterification reaction Methods 0.000 description 6
- OAMZXMDZZWGPMH-UHFFFAOYSA-N ethyl acetate;toluene Chemical compound CCOC(C)=O.CC1=CC=CC=C1 OAMZXMDZZWGPMH-UHFFFAOYSA-N 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- 150000003558 thiocarbamic acid derivatives Chemical class 0.000 description 6
- XSBHBYCNRIIYDF-BAFYGKSASA-N (6r)-4-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound OC(=O)C1=CC(N)S[C@@H]2CC(=O)N21 XSBHBYCNRIIYDF-BAFYGKSASA-N 0.000 description 5
- 238000006969 Curtius rearrangement reaction Methods 0.000 description 5
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Substances BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 5
- 239000007832 Na2SO4 Substances 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 5
- 150000001298 alcohols Chemical class 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 5
- 125000003277 amino group Chemical group 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- 239000002002 slurry Substances 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- OVYURQQBJSRSEQ-SSDOTTSWSA-N (6r)-3-isocyanato-5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical class S1CC(N=C=O)=CN2C(=O)C[C@H]21 OVYURQQBJSRSEQ-SSDOTTSWSA-N 0.000 description 4
- WDCWCSVXVOGANS-SSDOTTSWSA-N (6r)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-3-carbaldehyde Chemical class S1CC(C=O)=CN2C(=O)C[C@H]21 WDCWCSVXVOGANS-SSDOTTSWSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 4
- 150000001241 acetals Chemical class 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
- 150000007942 carboxylates Chemical class 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 230000008707 rearrangement Effects 0.000 description 4
- 150000003512 tertiary amines Chemical class 0.000 description 4
- 150000003573 thiols Chemical class 0.000 description 4
- KZLZXCMCARXUSX-XUNZJTMSSA-N (6r)-2-benzhydryloxycarbonyl-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-3-ene-3-carboxylic acid Chemical compound C1([C@H]2SC=C(C(N2C1=O)C(=O)OC(C=1C=CC=CC=1)C=1C=CC=CC=1)C(=O)O)NC(=O)CC1=CC=CS1 KZLZXCMCARXUSX-XUNZJTMSSA-N 0.000 description 3
- 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 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical group OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- ITLHXEGAYQFOHJ-UHFFFAOYSA-N [diazo(phenyl)methyl]benzene Chemical compound C=1C=CC=CC=1C(=[N+]=[N-])C1=CC=CC=C1 ITLHXEGAYQFOHJ-UHFFFAOYSA-N 0.000 description 3
- 230000009102 absorption Effects 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 3
- 238000005903 acid hydrolysis reaction Methods 0.000 description 3
- 238000006470 amide elimination reaction Methods 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000000845 anti-microbial effect Effects 0.000 description 3
- 239000006286 aqueous extract Substances 0.000 description 3
- 239000012300 argon atmosphere Substances 0.000 description 3
- 150000001540 azides Chemical class 0.000 description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 125000002843 carboxylic acid group Chemical group 0.000 description 3
- 150000001735 carboxylic acids Chemical class 0.000 description 3
- 150000005690 diesters Chemical class 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
- 150000004795 grignard reagents Chemical class 0.000 description 3
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 3
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 3
- 150000003141 primary amines Chemical class 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 150000003335 secondary amines Chemical class 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- UFHSNVJZECBUDN-HWZXHQHMSA-N (6R)-4-isocyanato-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylic acid Chemical compound C1[C@@H]2N(C1=O)C(C=C(S2)N=C=O)C(=O)O UFHSNVJZECBUDN-HWZXHQHMSA-N 0.000 description 2
- ITPIQUUKYMCDKH-SSDOTTSWSA-N (6r)-3-isocyanato-5-thia-1-azabicyclo[4.2.0]oct-3-en-8-one Chemical class C1C(N=C=O)=CS[C@@H]2CC(=O)N21 ITPIQUUKYMCDKH-SSDOTTSWSA-N 0.000 description 2
- HCQABJQZDYSTJH-QFSRMBNQSA-N (6r)-4-acetamido-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound OC(=O)C1=CC(NC(=O)C)S[C@@H]2CC(=O)N21 HCQABJQZDYSTJH-QFSRMBNQSA-N 0.000 description 2
- 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 2
- QITDACOZCQXYQY-BAFYGKSASA-N (6r)-7-amino-5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical class S1CC=CN2C(=O)C(N)[C@H]21 QITDACOZCQXYQY-BAFYGKSASA-N 0.000 description 2
- STBUIPVAMKHKBA-ZCFIWIBFSA-N (6r)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-3-carboxylic acid Chemical class S1CC(C(=O)O)=CN2C(=O)C[C@H]21 STBUIPVAMKHKBA-ZCFIWIBFSA-N 0.000 description 2
- PMBXCGGQNSVESQ-UHFFFAOYSA-N 1-Hexanethiol Chemical compound CCCCCCS PMBXCGGQNSVESQ-UHFFFAOYSA-N 0.000 description 2
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 2
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 2
- NWWJFMCCTZLKNT-UHFFFAOYSA-N 3,4-dihydro-2h-thiazine Chemical group C1CC=CSN1 NWWJFMCCTZLKNT-UHFFFAOYSA-N 0.000 description 2
- BGLAMXJBTZOWLK-UHFFFAOYSA-N 3-[[4-acetyl-2,3,6-trihydroxy-5-(3-methylbut-2-enyl)phenyl]methyl]-4-hydroxy-5,6-dimethylpyran-2-one Chemical compound OC1=C(C(C)=O)C(CC=C(C)C)=C(O)C(CC=2C(OC(C)=C(C)C=2O)=O)=C1O BGLAMXJBTZOWLK-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- 229910004373 HOAc Inorganic materials 0.000 description 2
- NPPQSCRMBWNHMW-UHFFFAOYSA-N Meprobamate Chemical compound NC(=O)OCC(C)(CCC)COC(N)=O NPPQSCRMBWNHMW-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- RTEXIPZMMDUXMR-UHFFFAOYSA-N benzene;ethyl acetate Chemical compound CCOC(C)=O.C1=CC=CC=C1 RTEXIPZMMDUXMR-UHFFFAOYSA-N 0.000 description 2
- MKFLFZPSOCGNJJ-PUUKEUDRSA-N benzhydryl (6r)-3-(1,3-dioxolan-2-yl)-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylate Chemical compound S([C@@H]12)C=C(C3OCCO3)C(C(=O)OC(C=3C=CC=CC=3)C=3C=CC=CC=3)N1C(=O)C2NC(=O)CC1=CC=CS1 MKFLFZPSOCGNJJ-PUUKEUDRSA-N 0.000 description 2
- MWKQSGCZBOXJPX-VCHQGTEKSA-N benzhydryl (6r)-3-[(4-nitrophenyl)methoxycarbonylamino]-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1=CC([N+](=O)[O-])=CC=C1COC(=O)NC1=C(C(=O)OC(C=2C=CC=CC=2)C=2C=CC=CC=2)N2C(=O)C(NC(=O)CC=3SC=CC=3)[C@H]2SC1 MWKQSGCZBOXJPX-VCHQGTEKSA-N 0.000 description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- MDHYEMXUFSJLGV-UHFFFAOYSA-N beta-phenethyl acetate Natural products CC(=O)OCCC1=CC=CC=C1 MDHYEMXUFSJLGV-UHFFFAOYSA-N 0.000 description 2
- 125000005997 bromomethyl group Chemical group 0.000 description 2
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
- LOCHFZBWPCLPAN-UHFFFAOYSA-N butane-2-thiol Chemical compound CCC(C)S LOCHFZBWPCLPAN-UHFFFAOYSA-N 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- FGSBWLZRBYZPAD-FYZOBXCZSA-N carbamic acid;(6r)-5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical class NC(O)=O.S1CC=CN2C(=O)C[C@H]21 FGSBWLZRBYZPAD-FYZOBXCZSA-N 0.000 description 2
- 235000013877 carbamide Nutrition 0.000 description 2
- 150000001733 carboxylic acid esters Chemical group 0.000 description 2
- XIURVHNZVLADCM-IUODEOHRSA-N cefalotin Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C(O)=O)C(=O)CC1=CC=CS1 XIURVHNZVLADCM-IUODEOHRSA-N 0.000 description 2
- 229960000603 cefalotin Drugs 0.000 description 2
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- JQVDAXLFBXTEQA-UHFFFAOYSA-N dibutylamine Chemical compound CCCCNCCCC JQVDAXLFBXTEQA-UHFFFAOYSA-N 0.000 description 2
- GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 2
- BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical compound COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 150000002483 hydrogen compounds Chemical class 0.000 description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 150000002641 lithium Chemical class 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 125000001979 organolithium group Chemical group 0.000 description 2
- JYVLIDXNZAXMDK-UHFFFAOYSA-N pentan-2-ol Chemical compound CCCC(C)O JYVLIDXNZAXMDK-UHFFFAOYSA-N 0.000 description 2
- ZUFQCVZBBNZMKD-UHFFFAOYSA-M potassium 2-ethylhexanoate Chemical compound [K+].CCCCC(CC)C([O-])=O ZUFQCVZBBNZMKD-UHFFFAOYSA-M 0.000 description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000000197 pyrolysis Methods 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 235000009518 sodium iodide Nutrition 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
- YPNHGNXITRZWIL-FBMWCMRBSA-N (4-methoxyphenyl)methyl (6r)-7-acetamido-3-isocyanato-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1=CC(OC)=CC=C1COC(=O)C1=C(N=C=O)CS[C@H]2N1C(=O)C2NC(C)=O YPNHGNXITRZWIL-FBMWCMRBSA-N 0.000 description 1
- FHXZRWVBDCAGTM-UUSAFJCLSA-N (6R)-3-(cyclohexyloxycarbonylamino)-7-[[2-(2,5-dichlorophenyl)ethanethioyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound ClC1=C(C=C(C=C1)Cl)CC(=S)NC1[C@@H]2N(C(=C(CS2)NC(=O)OC2CCCCC2)C(=O)O)C1=O FHXZRWVBDCAGTM-UUSAFJCLSA-N 0.000 description 1
- GPWLPLUTAAMJDS-ULUSZKPHSA-N (6R)-3-formyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylic acid Chemical compound C(=O)C1=CS[C@H]2N(C1C(=O)O)C(C2)=O GPWLPLUTAAMJDS-ULUSZKPHSA-N 0.000 description 1
- PBQOSGPCDPAFMN-FQNRMIAFSA-N (6R)-7-[(4-nitrophenyl)methoxycarbonylamino]-8-oxo-3-(propanoylamino)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CCC(=O)NC1=C(N2[C@@H](C(C2=O)NC(=O)OCC3=CC=C(C=C3)[N+](=O)[O-])SC1)C(=O)O PBQOSGPCDPAFMN-FQNRMIAFSA-N 0.000 description 1
- MWTYEGIFAJHYEW-NHXUYEQSSA-N (6R)-7-amino-3-(butan-2-yloxycarbonylamino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound NC1[C@@H]2N(C(=C(CS2)NC(=O)OC(C)CC)C(=O)O)C1=O MWTYEGIFAJHYEW-NHXUYEQSSA-N 0.000 description 1
- AQHOHEGLCWSKFI-GCZXYKMCSA-N (6R)-7-amino-4-[(3-methylphenyl)carbamoylamino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound NC1[C@@H]2N(C(=CC(S2)NC(=O)NC=2C=C(C=CC=2)C)C(=O)O)C1=O AQHOHEGLCWSKFI-GCZXYKMCSA-N 0.000 description 1
- CEARHYATNDCFMT-IOJJLOCKSA-N (6R)-7-amino-8-oxo-3-(propanoylamino)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound NC1[C@@H]2N(C(=C(CS2)NC(CC)=O)C(=O)O)C1=O CEARHYATNDCFMT-IOJJLOCKSA-N 0.000 description 1
- CTHONEVRBCIHRZ-RTYFJBAXSA-N (6R)-7-amino-8-oxo-4-(phenylcarbamoylamino)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C1=CC=C(C=C1)NC(=O)NC2C=C(N3[C@H](S2)C(C3=O)N)C(=O)O CTHONEVRBCIHRZ-RTYFJBAXSA-N 0.000 description 1
- FWBJZTHCBIXBAU-FBMWCMRBSA-N (6R)-8-oxo-7-[(2-phenoxyacetyl)amino]-3-(propanoylamino)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound O(C1=CC=CC=C1)CC(=O)NC1[C@@H]2N(C(=C(CS2)NC(CC)=O)C(=O)O)C1=O FWBJZTHCBIXBAU-FBMWCMRBSA-N 0.000 description 1
- VPBRWFUPRASNIU-RTYFJBAXSA-N (6R)-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2,3-dicarboxylic acid Chemical compound C1([C@@H]2N(C1=O)C(C(=CS2)C(O)=O)C(=O)O)NC(=O)CC1=CC=CS1 VPBRWFUPRASNIU-RTYFJBAXSA-N 0.000 description 1
- AOZWBOILSUIIBW-BLDCVEFLSA-N (6r)-3-(acetyloxymethyl)-7-methoxy-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylic acid Chemical compound S([C@@H]12)C=C(COC(C)=O)C(C(O)=O)N1C(=O)C2(OC)NC(=O)CC1=CC=CS1 AOZWBOILSUIIBW-BLDCVEFLSA-N 0.000 description 1
- DQTKVVVCBPRGMY-SBXXRYSUSA-N (6r)-3-(ethoxycarbonylamino)-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)NC(=O)OCC)C(O)=O)NC(=O)CC1=CC=CS1 DQTKVVVCBPRGMY-SBXXRYSUSA-N 0.000 description 1
- IKMMHGNDHPZROV-AEJJIKPWSA-N (6r)-3-[(3-ethoxy-2-ethoxycarbonyl-3-oxopropanoyl)amino]-7-[(2-formyloxy-2-phenylacetyl)amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)NC(=O)C(C(=O)OCC)C(=O)OCC)C(O)=O)NC(=O)C(OC=O)C1=CC=CC=C1 IKMMHGNDHPZROV-AEJJIKPWSA-N 0.000 description 1
- NNPFGUIBICGOMA-PVQCJRHBSA-N (6r)-3-[(3-methoxy-2-methoxycarbonyl-3-oxopropanoyl)amino]-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)NC(=O)C(C(=O)OC)C(=O)OC)C(O)=O)NC(=O)CC1=CC=CS1 NNPFGUIBICGOMA-PVQCJRHBSA-N 0.000 description 1
- QMPMLGCXMFAFCV-LRTDYKAYSA-N (6r)-3-[(4-nitrophenyl)methoxycarbonylamino]-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C1([C@H]2SCC(=C(N2C1=O)C(=O)O)NC(=O)OCC=1C=CC(=CC=1)[N+]([O-])=O)NC(=O)CC1=CC=CS1 QMPMLGCXMFAFCV-LRTDYKAYSA-N 0.000 description 1
- FUUNNFZBANIXJY-ZCFIWIBFSA-N (6r)-3-amino-5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical compound S1CC(N)=CN2C(=O)C[C@H]21 FUUNNFZBANIXJY-ZCFIWIBFSA-N 0.000 description 1
- QJJRYOGHRXARQD-FFFFSGIJSA-N (6r)-3-amino-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)N)C(O)=O)NC(=O)CC1=CC=CS1 QJJRYOGHRXARQD-FFFFSGIJSA-N 0.000 description 1
- VWKZOTOKKINGGP-GCZXYKMCSA-N (6r)-3-formyl-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylic acid Chemical compound C1([C@@H]2N(C1=O)C(C(=CS2)C=O)C(=O)O)NC(=O)CC1=CC=CS1 VWKZOTOKKINGGP-GCZXYKMCSA-N 0.000 description 1
- RHLBGAGAUSNVLN-HWZXHQHMSA-N (6r)-3-hydroxy-4-methyl-5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical class C1=C(O)C(C)S[C@@H]2CC(=O)N21 RHLBGAGAUSNVLN-HWZXHQHMSA-N 0.000 description 1
- ULFWYPUUIUGVOH-BAFYGKSASA-N (6r)-4-(carbamoylamino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound OC(=O)C1=CC(NC(=O)N)S[C@@H]2CC(=O)N21 ULFWYPUUIUGVOH-BAFYGKSASA-N 0.000 description 1
- LOLWRIYGFGQSBL-NQPNHJOESA-N (6r)-4-(hydroxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylic acid Chemical compound S1C(CO)=CC(C(O)=O)N2C(=O)C[C@H]21 LOLWRIYGFGQSBL-NQPNHJOESA-N 0.000 description 1
- VFCCKQIWSISKOY-NQPNHJOESA-N (6r)-4-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylic acid Chemical compound S1C(C)=CC(C(O)=O)N2C(=O)C[C@H]21 VFCCKQIWSISKOY-NQPNHJOESA-N 0.000 description 1
- PCXBUZDYIDVJLJ-RWWKDMOOSA-N (6r)-7-[[2-amino-2-(4-hydroxyphenyl)acetyl]amino]-8-oxo-3-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S([C@@H]1C(C(N1C=1C(O)=O)=O)NC(=O)C(N)C=2C=CC(O)=CC=2)CC=1NC(=O)CC1=CC=CC=C1 PCXBUZDYIDVJLJ-RWWKDMOOSA-N 0.000 description 1
- YTUBPWDWAUHJCB-WIXQSORDSA-N (6r)-7-acetamido-2-benzhydryloxycarbonyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-3-ene-3-carboxylic acid Chemical compound S([C@@H]1C(C(N11)=O)NC(=O)C)C=C(C(O)=O)C1C(=O)OC(C=1C=CC=CC=1)C1=CC=CC=C1 YTUBPWDWAUHJCB-WIXQSORDSA-N 0.000 description 1
- NQZLGKCDOQQESJ-JLOHTSLTSA-N (6r)-7-amino-3-(benzylsulfanylcarbonylamino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S([C@@H]1C(C(N1C=1C(O)=O)=O)N)CC=1NC(=O)SCC1=CC=CC=C1 NQZLGKCDOQQESJ-JLOHTSLTSA-N 0.000 description 1
- PDSDGDAZNQOCBI-HWZXHQHMSA-N (6r)-7-amino-3-(methoxycarbonylamino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1CC(NC(=O)OC)=C(C(O)=O)N2C(=O)C(N)[C@@H]12 PDSDGDAZNQOCBI-HWZXHQHMSA-N 0.000 description 1
- MTVIGYISURRXKV-OMNKOJBGSA-N (6r)-7-amino-3-(morpholine-4-carbonylamino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S([C@@H]1C(C(N1C=1C(O)=O)=O)N)CC=1NC(=O)N1CCOCC1 MTVIGYISURRXKV-OMNKOJBGSA-N 0.000 description 1
- XJFPKGDZTWXPMO-WCRCJTMVSA-N (6r)-7-benzamido-3-(carbamoylamino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)NC(=O)N)C(O)=O)NC(=O)C1=CC=CC=C1 XJFPKGDZTWXPMO-WCRCJTMVSA-N 0.000 description 1
- LULQMRKGOZKYFO-LWOQYNTDSA-N (6r)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2,3-dicarboxylic acid Chemical compound S1C=C(C(O)=O)C(C(=O)O)N2C(=O)C[C@H]21 LULQMRKGOZKYFO-LWOQYNTDSA-N 0.000 description 1
- ZMMRLWFGWQVVJD-UHFFFAOYSA-O (n,n-dimethylcarbamimidoyl)-dimethylazanium;azide Chemical compound [N-]=[N+]=[N-].CN(C)C(N)=[N+](C)C ZMMRLWFGWQVVJD-UHFFFAOYSA-O 0.000 description 1
- 125000001950 (p-hydroxyphenyl)glycinamido group Chemical group 0.000 description 1
- KPWDGTGXUYRARH-UHFFFAOYSA-N 2,2,2-trichloroethanol Chemical compound OCC(Cl)(Cl)Cl KPWDGTGXUYRARH-UHFFFAOYSA-N 0.000 description 1
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 1
- KLIDCXVFHGNTTM-UHFFFAOYSA-N 2,6-dimethoxyphenol Chemical group COC1=CC=CC(OC)=C1O KLIDCXVFHGNTTM-UHFFFAOYSA-N 0.000 description 1
- QUSTYFNPKBDELJ-UHFFFAOYSA-N 2-Pentanethiol Chemical compound CCCC(C)S QUSTYFNPKBDELJ-UHFFFAOYSA-N 0.000 description 1
- 125000005999 2-bromoethyl group Chemical group 0.000 description 1
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 1
- VNJOEUSYAMPBAK-UHFFFAOYSA-N 2-methylbenzenesulfonic acid;hydrate Chemical compound O.CC1=CC=CC=C1S(O)(=O)=O VNJOEUSYAMPBAK-UHFFFAOYSA-N 0.000 description 1
- XXQBDEXTKYJHHY-PUUKEUDRSA-N 2-o-benzhydryl 3-o-(2-bromoethyl) (6r)-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2,3-dicarboxylate Chemical compound C1([C@H]2SC=C(C(N2C1=O)C(=O)OC(C=1C=CC=CC=1)C=1C=CC=CC=1)C(=O)OCCBr)NC(=O)CC1=CC=CS1 XXQBDEXTKYJHHY-PUUKEUDRSA-N 0.000 description 1
- ALJACJOYTKTJOS-PUUKEUDRSA-N 2-o-benzhydryl 3-o-(2-iodoethyl) (6r)-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2,3-dicarboxylate Chemical compound C1([C@H]2SC=C(C(N2C1=O)C(=O)OC(C=1C=CC=CC=1)C=1C=CC=CC=1)C(=O)OCCI)NC(=O)CC1=CC=CS1 ALJACJOYTKTJOS-PUUKEUDRSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 1
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 1
- MSHFRERJPWKJFX-UHFFFAOYSA-N 4-Methoxybenzyl alcohol Chemical compound COC1=CC=C(CO)C=C1 MSHFRERJPWKJFX-UHFFFAOYSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- 125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 description 1
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 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 1
- NVIAYEIXYQCDAN-CLZZGJSISA-N 7beta-aminodeacetoxycephalosporanic acid Chemical compound S1CC(C)=C(C(O)=O)N2C(=O)[C@@H](N)[C@@H]12 NVIAYEIXYQCDAN-CLZZGJSISA-N 0.000 description 1
- LWRMVMBCRVWUAA-FYZOBXCZSA-N C(N)(O)=S.S1C=CCN2[C@H]1CC2=O Chemical compound C(N)(O)=S.S1C=CCN2[C@H]1CC2=O LWRMVMBCRVWUAA-FYZOBXCZSA-N 0.000 description 1
- 229910014033 C-OH Inorganic materials 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229910014570 C—OH Inorganic materials 0.000 description 1
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical class S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 101100295741 Gallus gallus COR4 gene Proteins 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 238000006644 Lossen rearrangement reaction Methods 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- WRQNANDWMGAFTP-UHFFFAOYSA-N Methylacetoacetic acid Chemical compound COC(=O)CC(C)=O WRQNANDWMGAFTP-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- GNVMUORYQLCPJZ-UHFFFAOYSA-M Thiocarbamate Chemical compound NC([S-])=O GNVMUORYQLCPJZ-UHFFFAOYSA-M 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- XAKBSHICSHRJCL-UHFFFAOYSA-N [CH2]C(=O)C1=CC=CC=C1 Chemical group [CH2]C(=O)C1=CC=CC=C1 XAKBSHICSHRJCL-UHFFFAOYSA-N 0.000 description 1
- 125000003647 acryloyl group Chemical group O=C([*])C([H])=C([H])[H] 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical group 0.000 description 1
- 125000005037 alkyl phenyl group Chemical group 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- GXLZSNTZHCLEPV-SLJLDQLWSA-N benzhydryl (6R)-3-(butanoylamino)-8-oxo-7-[(2-phenylsulfanylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1(=CC=CC=C1)SCC(=O)NC1[C@@H]2N(C(=C(CS2)NC(CCC)=O)C(=O)OC(C2=CC=CC=C2)C2=CC=CC=C2)C1=O GXLZSNTZHCLEPV-SLJLDQLWSA-N 0.000 description 1
- IJSDIZGTJFJPMI-GGYWIFMRSA-N benzhydryl (6R)-3-(butylsulfanylcarbonylamino)-7-[[2-(4-methoxyphenyl)-2-(phenylmethoxycarbonylamino)acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylate Chemical compound C(C1=CC=CC=C1)OC(=O)NC(C(=O)NC1[C@@H]2N(C(C(=CS2)NC(=O)SCCCC)C(=O)OC(C2=CC=CC=C2)C2=CC=CC=C2)C1=O)C1=CC=C(C=C1)OC IJSDIZGTJFJPMI-GGYWIFMRSA-N 0.000 description 1
- HPLNUGBKIUNYHA-IQHZPMLTSA-N benzhydryl (6R)-3-(ethoxycarbonylamino)-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S1C(=CC=C1)CC(=O)NC1[C@@H]2N(C(=C(CS2)NC(=O)OCC)C(=O)OC(C2=CC=CC=C2)C2=CC=CC=C2)C1=O HPLNUGBKIUNYHA-IQHZPMLTSA-N 0.000 description 1
- WGSNTYVIUAPGDY-GNVRUEKJSA-N benzhydryl (6R)-3-acetamido-7-[[3-[(2-methylpropan-2-yl)oxy]-3-oxo-2-phenylpropanoyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C(C)(C)(C)OC(=O)C(C(=O)NC1[C@@H]2N(C(=C(CS2)NC(C)=O)C(=O)OC(C2=CC=CC=C2)C2=CC=CC=C2)C1=O)C1=CC=CC=C1 WGSNTYVIUAPGDY-GNVRUEKJSA-N 0.000 description 1
- NRYPKZIUJYQMRW-AJEPASEPSA-N benzhydryl (6R)-3-carbonazidoyl-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylate Chemical compound S1C(=CC=C1)CC(=O)NC1[C@@H]2N(C(C(=CS2)C(=O)N=[N+]=[N-])C(=O)OC(C2=CC=CC=C2)C2=CC=CC=C2)C1=O NRYPKZIUJYQMRW-AJEPASEPSA-N 0.000 description 1
- OXCHVBHQEKCWCH-QEMNHKJVSA-N benzhydryl (6R)-8-oxo-7-[(2-phenylacetyl)amino]-4-(propan-2-ylcarbamoylamino)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1(=CC=CC=C1)CC(=O)NC1[C@@H]2N(C(=CC(S2)NC(=O)NC(C)C)C(=O)OC(C2=CC=CC=C2)C2=CC=CC=C2)C1=O OXCHVBHQEKCWCH-QEMNHKJVSA-N 0.000 description 1
- OREMAUXCVHJANR-IQHZPMLTSA-N benzhydryl (6r)-3-(carbamoylamino)-7-[[2-(2,5-dichlorophenyl)sulfanylacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)NC(=O)N)C(=O)OC(C=1C=CC=CC=1)C=1C=CC=CC=1)NC(=O)CSC1=CC(Cl)=CC=C1Cl OREMAUXCVHJANR-IQHZPMLTSA-N 0.000 description 1
- ZXLQUQGFMHZVLB-NOUYKBLCSA-N benzhydryl (6r)-3-[(4-methoxyphenyl)methoxycarbonylamino]-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1=CC(OC)=CC=C1COC(=O)NC1=C(C(=O)OC(C=2C=CC=CC=2)C=2C=CC=CC=2)N2C(=O)C(NC(=O)CC=3C=CC=CC=3)[C@H]2SC1 ZXLQUQGFMHZVLB-NOUYKBLCSA-N 0.000 description 1
- BWXKTOGKOGEFCK-ITCMONMYSA-N benzhydryl (6r)-3-acetamido-7-[(4-nitrophenyl)methoxycarbonylamino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)NC(=O)C)C(=O)OC(C=1C=CC=CC=1)C=1C=CC=CC=1)NC(=O)OCC1=CC=C([N+]([O-])=O)C=C1 BWXKTOGKOGEFCK-ITCMONMYSA-N 0.000 description 1
- QLOYSWDHYVXVNC-ITCMONMYSA-N benzhydryl (6r)-7-acetamido-3-[(4-nitrophenyl)methoxycarbonylamino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S([C@@H]1C(C(N1C=1C(=O)OC(C=2C=CC=CC=2)C=2C=CC=CC=2)=O)NC(=O)C)CC=1NC(=O)OCC1=CC=C([N+]([O-])=O)C=C1 QLOYSWDHYVXVNC-ITCMONMYSA-N 0.000 description 1
- XALZYBNNBZVOAS-XZZJRJTHSA-N benzhydryl (6r)-8-oxo-3-(phenylsulfanylcarbonylamino)-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylate Chemical compound S([C@@H]12)C=C(NC(=O)SC=3C=CC=CC=3)C(C(=O)OC(C=3C=CC=CC=3)C=3C=CC=CC=3)N1C(=O)C2NC(=O)CC1=CC=CS1 XALZYBNNBZVOAS-XZZJRJTHSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- UENWRTRMUIOCKN-UHFFFAOYSA-N benzyl thiol Chemical compound SCC1=CC=CC=C1 UENWRTRMUIOCKN-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- AOJDZKCUAATBGE-UHFFFAOYSA-N bromomethane Chemical compound Br[CH2] AOJDZKCUAATBGE-UHFFFAOYSA-N 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000006244 carboxylic acid protecting group Chemical group 0.000 description 1
- 238000001193 catalytic steam reforming Methods 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 229940117975 chromium trioxide Drugs 0.000 description 1
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 1
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000004802 cyanophenyl group Chemical group 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- JSYGRUBHOCKMGQ-UHFFFAOYSA-N dichloramine Chemical compound ClNCl JSYGRUBHOCKMGQ-UHFFFAOYSA-N 0.000 description 1
- SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 1
- FDSGHYHRLSWSLQ-UHFFFAOYSA-N dichloromethane;propan-2-one Chemical compound ClCCl.CC(C)=O FDSGHYHRLSWSLQ-UHFFFAOYSA-N 0.000 description 1
- JZUHYMSCMXKNHM-ZGKSLXBNSA-N diethyl 2-[[(6r)-2-benzhydryloxycarbonyl-8-oxo-7-(phenylmethoxycarbonylamino)-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]carbamoyl]propanedioate Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)NC(=O)C(C(=O)OCC)C(=O)OCC)C(=O)OC(C=1C=CC=CC=1)C=1C=CC=CC=1)NC(=O)OCC1=CC=CC=C1 JZUHYMSCMXKNHM-ZGKSLXBNSA-N 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 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 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- LXQXGFPPYLKKSD-UHFFFAOYSA-L disodium;2,2-diethylpropanedioate Chemical compound [Na+].[Na+].CCC(CC)(C([O-])=O)C([O-])=O LXQXGFPPYLKKSD-UHFFFAOYSA-L 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000006575 electron-withdrawing group Chemical group 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 125000006627 ethoxycarbonylamino group Chemical group 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000005059 halophenyl group Chemical group 0.000 description 1
- 125000000268 heptanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006038 hexenyl group Chemical group 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- IQPQWNKOIGAROB-UHFFFAOYSA-N isocyanate group Chemical group [N-]=C=O IQPQWNKOIGAROB-UHFFFAOYSA-N 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 229910000103 lithium hydride Inorganic materials 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 1
- LZFCBBSYZJPPIV-UHFFFAOYSA-M magnesium;hexane;bromide Chemical compound [Mg+2].[Br-].CCCCC[CH2-] LZFCBBSYZJPPIV-UHFFFAOYSA-M 0.000 description 1
- QGEFGPVWRJCFQP-UHFFFAOYSA-M magnesium;methanidylbenzene;bromide Chemical compound [Mg+2].[Br-].[CH2-]C1=CC=CC=C1 QGEFGPVWRJCFQP-UHFFFAOYSA-M 0.000 description 1
- LVKCSZQWLOVUGB-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].C[CH-]C LVKCSZQWLOVUGB-UHFFFAOYSA-M 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- ANGDWNBGPBMQHW-UHFFFAOYSA-N methyl cyanoacetate Chemical compound COC(=O)CC#N ANGDWNBGPBMQHW-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- HVAAHUDGWQAAOJ-UHFFFAOYSA-N n-benzylethanamine Chemical compound CCNCC1=CC=CC=C1 HVAAHUDGWQAAOJ-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- XHFGWHUWQXTGAT-UHFFFAOYSA-N n-methylpropan-2-amine Chemical compound CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000006501 nitrophenyl group Chemical group 0.000 description 1
- ODUCDPQEXGNKDN-UHFFFAOYSA-N nitroxyl Chemical compound O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 150000002900 organolithium compounds Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000033116 oxidation-reduction process Effects 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- SUVIGLJNEAMWEG-UHFFFAOYSA-N propane-1-thiol Chemical compound CCCS SUVIGLJNEAMWEG-UHFFFAOYSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000006894 reductive elimination reaction Methods 0.000 description 1
- IOVGROKTTNBUGK-SJCJKPOMSA-N ritodrine Chemical compound N([C@@H](C)[C@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJCJKPOMSA-N 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000002311 subsequent effect Effects 0.000 description 1
- ROALTDLWPFDGCQ-YDPRHXJPSA-N tert-butyl (6R)-7-[[2-(2,5-dichlorophenyl)sulfanylacetyl]amino]-8-oxo-4-(phenylcarbamoylamino)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound ClC1=C(C=C(C=C1)Cl)SCC(=O)NC1[C@@H]2N(C(=CC(S2)NC(=O)NC2=CC=CC=C2)C(=O)OC(C)(C)C)C1=O ROALTDLWPFDGCQ-YDPRHXJPSA-N 0.000 description 1
- LJKUASXHOMAWDB-FAFZWHIHSA-N tert-butyl (6R)-7-[[2-(2-chlorophenoxy)acetyl]amino]-3-(ethoxycarbonylamino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylate Chemical compound ClC1=C(OCC(=O)NC2[C@@H]3N(C(C(=CS3)NC(=O)OCC)C(=O)OC(C)(C)C)C2=O)C=CC=C1 LJKUASXHOMAWDB-FAFZWHIHSA-N 0.000 description 1
- JSYWTBPIWUNAEO-GZNCHQMQSA-N tert-butyl (6R)-8-oxo-4-(pentylcarbamoylamino)-7-(phenylmethoxycarbonylamino)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C(C1=CC=CC=C1)OC(=O)NC1[C@@H]2N(C(=CC(S2)NC(=O)NCCCCC)C(=O)OC(C)(C)C)C1=O JSYWTBPIWUNAEO-GZNCHQMQSA-N 0.000 description 1
- JBBRZZPSDYNXAN-LMNIDFBRSA-N tert-butyl (6r)-3-benzamido-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1([C@H]2SCC(=C(N2C1=O)C(=O)OC(C)(C)C)NC(=O)C=1C=CC=CC=1)NC(=O)CC1=CC=CS1 JBBRZZPSDYNXAN-LMNIDFBRSA-N 0.000 description 1
- OLLXOMJNKRSWLF-FFFFSGIJSA-N tert-butyl (6r)-7-amino-8-oxo-3-(propan-2-yloxycarbonylamino)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S1CC(NC(=O)OC(C)C)=C(C(=O)OC(C)(C)C)N2C(=O)C(N)[C@@H]12 OLLXOMJNKRSWLF-FFFFSGIJSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 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
- C07D501/57—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
-
- 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
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Cephalosporin Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/529,676 US4001226A (en) | 1974-12-04 | 1974-12-04 | 3-(substituted)carbonylamino cephem derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1041480A true CA1041480A (en) | 1978-10-31 |
Family
ID=24110865
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA237,187A Expired CA1041480A (en) | 1974-12-04 | 1975-10-07 | 3-(substituted) carbonylamino cephem derivatives |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US4001226A (en, 2012) |
| JP (2) | JPS6133838B2 (en, 2012) |
| BE (2) | BE836294A (en, 2012) |
| CA (1) | CA1041480A (en, 2012) |
| CH (1) | CH623825A5 (en, 2012) |
| DE (2) | DE2553914A1 (en, 2012) |
| FR (2) | FR2293206A1 (en, 2012) |
| GB (1) | GB1525739A (en, 2012) |
| IE (1) | IE41864B1 (en, 2012) |
| IL (2) | IL48284A (en, 2012) |
| NL (2) | NL7514000A (en, 2012) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4013651A (en) * | 1975-05-12 | 1977-03-22 | Eli Lilly And Company | 3-substituted amino-cephalosporins |
| US4436903A (en) | 1980-12-22 | 1984-03-13 | Ciba-Geigy Corporation | Process for the production of 7 β-substituted-3-unsubstituted-3-cephem-4-carboxylic acid compounds |
| US4521598A (en) * | 1983-09-28 | 1985-06-04 | Eli Lilly And Company | 3-Azidocephalosporins |
| US4560749A (en) * | 1983-11-18 | 1985-12-24 | Eli Lilly And Company | Cephem-3-imidates and 3-amidines |
| US6133444A (en) * | 1993-12-22 | 2000-10-17 | Perseptive Biosystems, Inc. | Synthons for the synthesis and deprotection of peptide nucleic acids under mild conditions |
| WO1996040709A1 (en) * | 1995-06-07 | 1996-12-19 | Perseptive Biosystems, Inc. | Pna-dna chimeras and pna synthons for their preparation |
| AR035728A1 (es) * | 2001-01-16 | 2004-07-07 | Merck & Co Inc | Proceso perfeccionado para la sintesis de carbapenem |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA713229B (en) * | 1970-06-16 | 1972-01-26 | Merck & Co Inc | Anti biotics and processes for their production |
-
1974
- 1974-12-04 US US05/529,676 patent/US4001226A/en not_active Expired - Lifetime
-
1975
- 1975-10-03 IE IE2173/75A patent/IE41864B1/en unknown
- 1975-10-07 CA CA237,187A patent/CA1041480A/en not_active Expired
- 1975-10-10 IL IL48284A patent/IL48284A/xx unknown
- 1975-11-05 IL IL48429A patent/IL48429A0/xx unknown
- 1975-11-27 GB GB48753/75A patent/GB1525739A/en not_active Expired
- 1975-11-27 JP JP50142153A patent/JPS6133838B2/ja not_active Expired
- 1975-11-27 JP JP50142154A patent/JPS5191285A/ja active Pending
- 1975-12-01 DE DE19752553914 patent/DE2553914A1/de active Pending
- 1975-12-01 DE DE19752553912 patent/DE2553912A1/de not_active Withdrawn
- 1975-12-01 NL NL7514000A patent/NL7514000A/xx unknown
- 1975-12-03 NL NL7514113A patent/NL7514113A/xx not_active Application Discontinuation
- 1975-12-03 CH CH1573075A patent/CH623825A5/de not_active IP Right Cessation
- 1975-12-04 BE BE1007053A patent/BE836294A/xx not_active IP Right Cessation
- 1975-12-04 BE BE1007054A patent/BE836295A/xx not_active IP Right Cessation
- 1975-12-04 FR FR7537115A patent/FR2293206A1/fr active Granted
- 1975-12-04 FR FR7537116A patent/FR2293207A1/fr active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| GB1525739A (en) | 1978-09-20 |
| JPS6133838B2 (en, 2012) | 1986-08-04 |
| IE41864B1 (en) | 1980-04-09 |
| CH623825A5 (en, 2012) | 1981-06-30 |
| BE836294A (fr) | 1976-06-04 |
| FR2293206B1 (en, 2012) | 1978-11-10 |
| IE41864L (en) | 1976-06-04 |
| IL48284A0 (en) | 1975-12-31 |
| JPS5191285A (en, 2012) | 1976-08-10 |
| DE2553912A1 (de) | 1976-06-16 |
| FR2293207B1 (en, 2012) | 1978-07-28 |
| BE836295A (fr) | 1976-06-04 |
| IL48284A (en) | 1980-09-16 |
| DE2553914A1 (de) | 1976-06-10 |
| FR2293206A1 (fr) | 1976-07-02 |
| IL48429A0 (en) | 1976-01-30 |
| JPS5176288A (en, 2012) | 1976-07-01 |
| NL7514113A (nl) | 1976-06-09 |
| US4001226A (en) | 1977-01-04 |
| NL7514000A (nl) | 1976-06-09 |
| FR2293207A1 (fr) | 1976-07-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA1039270A (en) | 3-thio-substituted cephalosporin antibiotics | |
| NZ193317A (en) | 7-(2-(2-amino-4-thiazolyl)-2-((1-carboxy-1,1-dialkyl)-alkoxyimino)-acetamido)-cephem sulphoxide derivatives and pharmaceutical compositions | |
| US3917587A (en) | Cephalosporin ethers | |
| CA1041480A (en) | 3-(substituted) carbonylamino cephem derivatives | |
| EP0002605B1 (en) | Cephalosporin compounds and formulations containing them for use in the treatment of bacterial infections and the preparation of the cephalosporin compounds | |
| US3917588A (en) | {60 -Aminoacyl cephalosporin ethers | |
| US3632850A (en) | Cephalexin synthesis | |
| US3849408A (en) | 4-substituted-delta2-cephalosporin derivatives | |
| GB2071654A (en) | Hydroxamic acid derivatives of 7-(2-amino-4-thiazolyl)oximino cephalosporins | |
| JPH04225985A (ja) | セフアロスポリン化合物 | |
| US4012380A (en) | 7-Acylamino-3-acyl-2(or 3)cephems | |
| US4018921A (en) | Substituted phenylglycylcephalosporins | |
| US4943631A (en) | Process for cephem compounds | |
| US3769280A (en) | Process for acylation of cephalosporin esters | |
| US4521598A (en) | 3-Azidocephalosporins | |
| US4560683A (en) | Cephalosporin antibiotics | |
| CA1043332A (en) | 3,4-dicarboxycephalosporins and derivatives | |
| US3853861A (en) | Cephalexin intermediate | |
| CS216938B2 (en) | Method of making the derivatives of the 7 beta-aminothiazolylycetamido-3-cefem-4-carboxyl acid | |
| US3840532A (en) | Process for cleaving cephalosporin compounds | |
| GB2165245A (en) | Chemical compounds | |
| EP0122158A2 (en) | Improvements in or relating to benzothienyl cephalosporin antibiotics | |
| US4107440A (en) | Intermediates for preparing substituted phenylglycylcephalosporins | |
| US4044047A (en) | Intermediates for preparing substituted phenylglycylcephalosporins | |
| GB2132193A (en) | Cephalosporin antibiotics |