AP832A - 3-Tetrahydrofuran and tetrohydropyrinol ephynolsporens and analogues. - Google Patents

3-Tetrahydrofuran and tetrohydropyrinol ephynolsporens and analogues. Download PDF

Info

Publication number: AP832A
Authority: AP; ARIPO
Prior art keywords: carboxylate; tetrahydrofuran; ceph; compound; aminothiazol
Prior art date: 1990-07-24

Application number

APAP/P/1991/000305A

Other languages

English (en)

Other versions

AP9100305A0 (en

Inventor

John Hargreaves Bateson

Stephen Christopher Martin Fell

George Burton

Original Assignee

Beecham Group Plc

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1990-07-24

Filing date

1991-07-22

Publication date

2000-05-03

1990-07-24 Priority claimed from GB909016189A external-priority patent/GB9016189D0/en

1991-05-02 Priority claimed from GB919109540A external-priority patent/GB9109540D0/en

1991-07-22 Application filed by Beecham Group Plc filed Critical Beecham Group Plc

1991-07-31 Publication of AP9100305A0 publication Critical patent/AP9100305A0/xx

2000-05-03 Application granted granted Critical

2000-05-03 Publication of AP832A publication Critical patent/AP832A/en

Links

WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 title description 35
-1 formamido Chemical group 0.000 claims abstract description 69
150000003839 salts Chemical class 0.000 claims abstract description 39
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 16
150000001875 compounds Chemical class 0.000 claims description 150
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 claims description 32
229910052708 sodium Inorganic materials 0.000 claims description 32
239000011734 sodium Substances 0.000 claims description 32
239000002253 acid Substances 0.000 claims description 31
150000002148 esters Chemical class 0.000 claims description 31
238000000034 method Methods 0.000 claims description 31
238000001727 in vivo Methods 0.000 claims description 29
125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 25
238000002360 preparation method Methods 0.000 claims description 12
239000003814 drug Substances 0.000 claims description 11
238000005917 acylation reaction Methods 0.000 claims description 10
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 6
230000010933 acylation Effects 0.000 claims description 5
239000003781 beta lactamase inhibitor Substances 0.000 claims description 5
229940126813 beta-lactamase inhibitor Drugs 0.000 claims description 5
125000003277 amino group Chemical group 0.000 claims description 4
150000004292 cyclic ethers Chemical group 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 3
125000006239 protecting group Chemical group 0.000 claims description 3
125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
229940126085 β‑Lactamase Inhibitor Drugs 0.000 claims description 3
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
MYJSNLKUTOLHSV-SVLLLCHKSA-N tert-butyl (6r,7r)-7-amino-8-oxo-3-(oxolan-2-yl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound O=C([C@@H](N)[C@H]1SC2)N1C(C(=O)OC(C)(C)C)=C2C1CCCO1 MYJSNLKUTOLHSV-SVLLLCHKSA-N 0.000 claims description 2
MOMMCCDMOQXKGH-NZMWDFQUSA-N 1-propan-2-yloxycarbonyloxyethyl (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-8-oxo-3-[(2S)-oxolan-2-yl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound NC=1SC=C(N=1)/C(/C(=O)N[C@H]1[C@@H]2N(C(=C(CS2)[C@H]2OCCC2)C(=O)OC(C)OC(=O)OC(C)C)C1=O)=N/OC MOMMCCDMOQXKGH-NZMWDFQUSA-N 0.000 claims 1
FMSUTPHWDFNQNO-MBVQEMHOSA-N 2,2-dimethylpropanoyloxymethyl (6r,7r)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-8-oxo-3-[(2r)-oxolan-2-yl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S([C@@H]1[C@@H](C(N1C=1C(=O)OCOC(=O)C(C)(C)C)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1[C@H]1CCCO1 FMSUTPHWDFNQNO-MBVQEMHOSA-N 0.000 claims 1
FMSUTPHWDFNQNO-NBXBADPDSA-N 2,2-dimethylpropanoyloxymethyl (6r,7r)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-8-oxo-3-[(2s)-oxolan-2-yl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S([C@@H]1[C@@H](C(N1C=1C(=O)OCOC(=O)C(C)(C)C)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1[C@@H]1CCCO1 FMSUTPHWDFNQNO-NBXBADPDSA-N 0.000 claims 1
230000001580 bacterial effect Effects 0.000 claims 1
229910052739 hydrogen Inorganic materials 0.000 abstract description 14
239000001257 hydrogen Substances 0.000 abstract description 12
208000035143 Bacterial infection Diseases 0.000 abstract description 8
208000022362 bacterial infectious disease Diseases 0.000 abstract description 8
125000001424 substituent group Chemical group 0.000 abstract description 5
125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 4
241001465754 Metazoa Species 0.000 abstract description 3
239000003782 beta lactam antibiotic agent Substances 0.000 abstract description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 abstract description 2
125000002252 acyl group Chemical group 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 252
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 113
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 108
229940093499 ethyl acetate Drugs 0.000 description 84
235000019439 ethyl acetate Nutrition 0.000 description 84
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 76
239000000203 mixture Substances 0.000 description 72
239000000243 solution Substances 0.000 description 67
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 54
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
238000001819 mass spectrum Methods 0.000 description 49
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 45
150000002500 ions Chemical class 0.000 description 41
239000006260 foam Substances 0.000 description 31
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 28
239000012267 brine Substances 0.000 description 27
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
125000000217 alkyl group Chemical group 0.000 description 24
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 24
239000011541 reaction mixture Substances 0.000 description 24
239000000741 silica gel Substances 0.000 description 24
229910002027 silica gel Inorganic materials 0.000 description 24
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 23
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 22
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 21
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 21
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
238000003818 flash chromatography Methods 0.000 description 20
238000006243 chemical reaction Methods 0.000 description 19
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 18
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 16
PJUIMOJAAPLTRJ-UHFFFAOYSA-N monothioglycerol Chemical compound OCC(O)CS PJUIMOJAAPLTRJ-UHFFFAOYSA-N 0.000 description 16
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 16
239000000047 product Substances 0.000 description 16
239000002904 solvent Substances 0.000 description 16
229940035024 thioglycerol Drugs 0.000 description 16
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 16
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
229910052943 magnesium sulfate Inorganic materials 0.000 description 15
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 13
125000000623 heterocyclic group Chemical group 0.000 description 12
229910000027 potassium carbonate Inorganic materials 0.000 description 12
239000007787 solid Substances 0.000 description 12
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 11
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 11
239000003921 oil Substances 0.000 description 11
235000019198 oils Nutrition 0.000 description 11
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
239000001632 sodium acetate Substances 0.000 description 11
235000017281 sodium acetate Nutrition 0.000 description 11
238000003756 stirring Methods 0.000 description 11
CWNPOQFCIIFQDM-UHFFFAOYSA-N 3-nitrobenzyl alcohol Chemical compound OCC1=CC=CC([N+]([O-])=O)=C1 CWNPOQFCIIFQDM-UHFFFAOYSA-N 0.000 description 10
125000003545 alkoxy group Chemical group 0.000 description 10
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 10
125000003118 aryl group Chemical group 0.000 description 10
150000001780 cephalosporins Chemical class 0.000 description 10
239000003795 chemical substances by application Substances 0.000 description 10
229910052736 halogen Inorganic materials 0.000 description 10
150000002367 halogens Chemical class 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
229930186147 Cephalosporin Natural products 0.000 description 9
229910052786 argon Inorganic materials 0.000 description 9
229940124587 cephalosporin Drugs 0.000 description 9
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 9
235000017557 sodium bicarbonate Nutrition 0.000 description 9
229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 8
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 8
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 8
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 8
238000010626 work up procedure Methods 0.000 description 8
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 7
XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 7
238000004587 chromatography analysis Methods 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
150000002431 hydrogen Chemical class 0.000 description 7
239000012074 organic phase Substances 0.000 description 7
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
238000000746 purification Methods 0.000 description 7
239000003981 vehicle Substances 0.000 description 7
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 6
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 6
229910021529 ammonia Inorganic materials 0.000 description 6
MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical class O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 description 6
150000001782 cephems Chemical class 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
239000007858 starting material Substances 0.000 description 6
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 5
238000004458 analytical method Methods 0.000 description 5
239000002585 base Substances 0.000 description 5
125000004432 carbon atom Chemical group C* 0.000 description 5
239000006071 cream Substances 0.000 description 5
125000004185 ester group Chemical group 0.000 description 5
235000019441 ethanol Nutrition 0.000 description 5
150000004820 halides Chemical class 0.000 description 5
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 5
229910052757 nitrogen Inorganic materials 0.000 description 5
239000000725 suspension Substances 0.000 description 5
TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 5
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
239000005711 Benzoic acid Substances 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
125000004453 alkoxycarbonyl group Chemical group 0.000 description 4
150000008064 anhydrides Chemical class 0.000 description 4
239000003242 anti bacterial agent Substances 0.000 description 4
235000010233 benzoic acid Nutrition 0.000 description 4
230000003115 biocidal effect Effects 0.000 description 4
125000000753 cycloalkyl group Chemical group 0.000 description 4
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 4
239000000284 extract Substances 0.000 description 4
229910000042 hydrogen bromide Inorganic materials 0.000 description 4
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
229910000041 hydrogen chloride Inorganic materials 0.000 description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
239000012442 inert solvent Substances 0.000 description 4
239000000543 intermediate Substances 0.000 description 4
239000007788 liquid Substances 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
JWEQRJSCTFBRSI-PCLIKHOPSA-N rboxylate Chemical compound COC(=O)C1C(N2C3=O)C4=CC=CC=C4OC1(C)N=C2S\C3=C\C(C=1)=CC=C(OC)C=1COC1=CC=CC=C1C JWEQRJSCTFBRSI-PCLIKHOPSA-N 0.000 description 4
229920006395 saturated elastomer Polymers 0.000 description 4
229940124597 therapeutic agent Drugs 0.000 description 4
IAWVHZJZHDSEOC-UHFFFAOYSA-M 3,3-dimethyl-2-oxobutanoate Chemical compound CC(C)(C)C(=O)C([O-])=O IAWVHZJZHDSEOC-UHFFFAOYSA-M 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
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
241000588724 Escherichia coli Species 0.000 description 3
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 3
241000400611 Eucalyptus deanei Species 0.000 description 3
241000282412 Homo Species 0.000 description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
239000012359 Methanesulfonyl chloride Substances 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
125000002947 alkylene group Chemical group 0.000 description 3
239000000908 ammonium hydroxide Substances 0.000 description 3
229940088710 antibiotic agent Drugs 0.000 description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
239000011230 binding agent Substances 0.000 description 3
ACBDNFPUXYGKPT-UHFFFAOYSA-N bromomethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCBr ACBDNFPUXYGKPT-UHFFFAOYSA-N 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
125000001309 chloro group Chemical group Cl* 0.000 description 3
238000001816 cooling Methods 0.000 description 3
238000010828 elution Methods 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
235000019253 formic acid Nutrition 0.000 description 3
238000009472 formulation Methods 0.000 description 3
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
239000003755 preservative agent Substances 0.000 description 3
229910052705 radium Inorganic materials 0.000 description 3
229910052701 rubidium Inorganic materials 0.000 description 3
235000009518 sodium iodide Nutrition 0.000 description 3
239000000600 sorbitol Substances 0.000 description 3
235000010356 sorbitol Nutrition 0.000 description 3
239000006188 syrup Substances 0.000 description 3
235000020357 syrup Nutrition 0.000 description 3
239000003826 tablet Substances 0.000 description 3
125000003396 thiol group Chemical class [H]S* 0.000 description 3
150000003573 thiols Chemical class 0.000 description 3
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QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 1
WHMDPDGBKYUEMW-UHFFFAOYSA-N pyridine-2-thiol Chemical compound SC1=CC=CC=N1 WHMDPDGBKYUEMW-UHFFFAOYSA-N 0.000 description 1
150000003222 pyridines Chemical class 0.000 description 1
MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
239000012048 reactive intermediate Substances 0.000 description 1
238000007142 ring opening reaction Methods 0.000 description 1
125000006413 ring segment Chemical group 0.000 description 1
238000007789 sealing Methods 0.000 description 1
238000000926 separation method Methods 0.000 description 1
238000007086 side reaction Methods 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 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
159000000000 sodium salts Chemical class 0.000 description 1
QRIBXVGHDLFNNE-DQJGWHCYSA-M sodium;(6r,7r)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-8-oxo-3-(oxolan-2-yl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound [Na+].S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1C1CCCO1 QRIBXVGHDLFNNE-DQJGWHCYSA-M 0.000 description 1
QRIBXVGHDLFNNE-PEMQHITISA-M sodium;(6r,7r)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-8-oxo-3-[(2r)-oxolan-2-yl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound [Na+].S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1[C@H]1CCCO1 QRIBXVGHDLFNNE-PEMQHITISA-M 0.000 description 1
GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
235000010199 sorbic acid Nutrition 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
238000001228 spectrum Methods 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
125000003638 stannyl group Chemical group [H][Sn]([H])([H])* 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
238000004659 sterilization and disinfection Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000002511 suppository base Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
239000002278 tabletting lubricant Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
GAMMOYWIGOUVQR-MDLDFJCZSA-N tert-butyl (6r,7r)-7-amino-3-(oxan-2-yl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound O=C([C@@H](N)[C@H]1SC2)N1C(C(=O)OC(C)(C)C)=C2C1CCCCO1 GAMMOYWIGOUVQR-MDLDFJCZSA-N 0.000 description 1
VDIBVAKPTLIVJC-QHNQYTFYSA-N tert-butyl (6r,7r)-8-oxo-3-(oxolan-2-yl)-7-[(2-phenoxyacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound N([C@H]1[C@H]2SCC(=C(N2C1=O)C(=O)OC(C)(C)C)C1OCCC1)C(=O)COC1=CC=CC=C1 VDIBVAKPTLIVJC-QHNQYTFYSA-N 0.000 description 1
MTOYIDLPMZXRBE-HJSRJYPHSA-N tert-butyl 2-chloro-2-[(2r,3r)-2-[2-(oxan-2-yl)-2-oxoethyl]sulfanyl-4-oxo-3-[(2-phenylacetyl)amino]azetidin-1-yl]acetate Chemical compound S([C@H]1N(C([C@H]1NC(=O)CC=1C=CC=CC=1)=O)C(Cl)C(=O)OC(C)(C)C)CC(=O)C1CCCCO1 MTOYIDLPMZXRBE-HJSRJYPHSA-N 0.000 description 1
YCXJNMHYSAAGSG-ITYAMSQCSA-N tert-butyl 2-hydroxy-2-[(2r,3r)-2-[2-(oxan-2-yl)-2-oxoethyl]sulfanyl-4-oxo-3-[(2-phenylacetyl)amino]azetidin-1-yl]acetate Chemical compound S([C@H]1N(C([C@H]1NC(=O)CC=1C=CC=CC=1)=O)C(O)C(=O)OC(C)(C)C)CC(=O)C1CCCCO1 YCXJNMHYSAAGSG-ITYAMSQCSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
125000005556 thienylene group Chemical group 0.000 description 1
239000012049 topical pharmaceutical composition Substances 0.000 description 1
230000002110 toxicologic effect Effects 0.000 description 1
231100000759 toxicological effect Toxicity 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
125000004665 trialkylsilyl group Chemical group 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
GYNCCYBVXKBGJL-UHFFFAOYSA-N tributyl(oxolan-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1CCCO1 GYNCCYBVXKBGJL-UHFFFAOYSA-N 0.000 description 1
DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical group CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 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
DGIJAZGPLFOQJE-UHFFFAOYSA-N trimethylsilyl n-trimethylsilylcarbamate Chemical compound C[Si](C)(C)NC(=O)O[Si](C)(C)C DGIJAZGPLFOQJE-UHFFFAOYSA-N 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
238000010792 warming Methods 0.000 description 1
150000003952 β-lactams Chemical class 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
- 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
- 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
- C07D463/00—Heterocyclic compounds containing 1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbacephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D463/10—Heterocyclic compounds containing 1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbacephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
- C07D463/14—Heterocyclic compounds containing 1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbacephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2 with hetero atoms directly attached in position 7
- C07D463/16—Nitrogen atoms
- C07D463/18—Nitrogen atoms further acylated by radicals derived from carboxylic acids or by nitrogen or sulfur analogues thereof
- C07D463/20—Nitrogen atoms further acylated by radicals derived from carboxylic acids or by nitrogen or sulfur analogues thereof with the acylating radicals further substituted by hetero atoms or by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D463/22—Nitrogen atoms further acylated by radicals derived from carboxylic acids or by nitrogen or sulfur analogues thereof with the acylating radicals further substituted by hetero atoms or by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen further substituted by nitrogen atoms
- 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)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

APAP/P/1991/000305A 1990-07-24 1991-07-22 3-Tetrahydrofuran and tetrohydropyrinol ephynolsporens and analogues. AP832A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB909016189A GB9016189D0 (en)	1990-07-24	1990-07-24	Novel compounds
GB919109540A GB9109540D0 (en)	1991-05-02	1991-05-02	Novel compounds

Publications (2)

Publication Number	Publication Date
AP9100305A0 AP9100305A0 (en)	1991-07-31
AP832A true AP832A (en)	2000-05-03

Family

ID=26297372

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
APAP/P/1991/000305A AP832A (en)	1990-07-24	1991-07-22	3-Tetrahydrofuran and tetrohydropyrinol ephynolsporens and analogues.

Country Status (26)

Country	Link
EP (2)	EP0540606A1 (de)
JP (2)	JP2851428B2 (de)
KR (1)	KR100189075B1 (de)
CN (2)	CN1061046C (de)
AP (1)	AP832A (de)
AT (1)	ATE185567T1 (de)
AU (1)	AU648329B2 (de)
CA (2)	CA2359744C (de)
CZ (1)	CZ6493A3 (de)
DE (2)	DE122006000065I2 (de)
DK (1)	DK0540609T3 (de)
ES (1)	ES2137162T3 (de)
FI (1)	FI930270A7 (de)
GR (1)	GR3031711T3 (de)
HU (1)	HUT63628A (de)
IE (1)	IE912569A1 (de)
IL (1)	IL98909A0 (de)
LU (1)	LU91290I2 (de)
MX (1)	MX9100317A (de)
MY (1)	MY106399A (de)
NL (1)	NL300249I2 (de)
NO (1)	NO930226L (de)
NZ (1)	NZ239061A (de)
PT (1)	PT98426A (de)
WO (2)	WO1992001696A1 (de)
YU (1)	YU129691A (de)

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GB9125645D0 (en) *	1991-12-03	1992-01-29	Smithkline Beecham Plc	Novel compounds
JPH07503460A (ja) *	1992-01-22	1995-04-13	ファイザー・インコーポレイテッド	２−イソセフェムおよびオキサセファム誘導体，それらの製法，その中間体および抗菌剤としての使用
GB9212609D0 (en) *	1992-06-13	1992-07-29	Smithkline Beecham Plc	Novel compounds
GB9213567D0 (en) *	1992-06-26	1992-08-12	Smithkline Beecham Plc	Novel compounds
GB9424847D0 (en) *	1994-12-09	1995-02-08	Smithkline Beecham Plc	Novel process
GB2300856A (en) *	1995-05-16	1996-11-20	Pfizer Ltd	Beta-lactam preparation
AU4398297A (en) *	1996-10-02	1998-04-24	Daiichi Pharmaceutical Co., Ltd.	Method for esterifying carboxylic compounds
FR2776292B1 (fr)	1998-03-20	2004-09-10	Oncopharm	Cephalotaxanes porteurs de chaine laterale et leur procede de synthese
GB0019124D0 (en)	2000-08-03	2000-09-27	Pfizer	Novel process
ES2257471T3 (es) *	2000-12-04	2006-08-01	Pfizer Products Inc.	Procedimiento y derivados esteres utiles para la preparacion de cefalosporinas.
KR100526379B1 (ko) *	2000-12-04	2005-11-08	화이자 프로덕츠 인크.	세팔로스포린 제조에 유용한 커플링법 및 중간체
US7378408B2 (en) *	2001-11-30	2008-05-27	Pfizer Inc.	Methods of treatment and formulations of cephalosporin
KR100710555B1 (ko)	2001-12-04	2007-04-24	에스케이 주식회사	광학적으로 순수한 (ｒ)-폼 또는 (ｓ)-폼의테트라히드로퓨라닐 케톤의 제조방법
UA117095C2 (uk)	2011-12-22	2018-06-25	Аліос Біофарма, Інк.	Нуклеозидна сполука або її фармацевтично прийнятна сіль
USRE48171E1 (en)	2012-03-21	2020-08-25	Janssen Biopharma, Inc.	Substituted nucleosides, nucleotides and analogs thereof
US9441007B2 (en)	2012-03-21	2016-09-13	Alios Biopharma, Inc.	Substituted nucleosides, nucleotides and analogs thereof
SG11201407336PA (en)	2012-05-25	2015-03-30	Janssen Sciences Ireland Uc	Uracyl spirooxetane nucleosides
KR102788773B1 (ko)	2012-12-21	2025-03-28	얀센 바이오파마, 인코퍼레이트.	치환된 뉴클레오사이드, 뉴클레오타이드 및 그것의 유사체
CN105254648B (zh) *	2015-11-13	2018-04-03	广东温氏大华农生物科技有限公司	一种头孢维星及其钠盐的合成方法
GB2575261B (en)	2018-07-02	2022-03-09	Norbrook Lab Ltd	Intermediates in the synthesis of C3-substituted cephalosporins
SG11202101429YA (en)	2018-08-23	2021-03-30	Seagen Inc	Anti-tigit antibodies
BR112022010924A2 (pt)	2019-12-06	2022-09-06	Vertex Pharma	Tetra-hidrofuranos substituídos como moduladores de canais de sódio
CN115135383B (zh)	2020-02-18	2024-06-11	吉利德科学公司	抗病毒化合物
TWI874791B (zh)	2020-02-18	2025-03-01	美商基利科學股份有限公司	抗病毒化合物
TWI883391B (zh)	2020-02-18	2025-05-11	美商基利科學股份有限公司	抗病毒化合物
CN111620893B (zh) *	2020-06-08	2021-12-14	重庆医药高等专科学校	C-3位四氢呋喃取代的头孢菌素-铁载体耦合物及其制备方法和应用
CA3216162A1 (en)	2021-04-16	2022-10-20	Gilead Sciences, Inc.	Methods of preparing carbanucleosides using amides
KR20240031300A (ko)	2021-06-04	2024-03-07	버텍스 파마슈티칼스 인코포레이티드	나트륨 채널 조절제로서의 n-(하이드록시알킬 (헤테로)아릴) 테트라하이드로푸란 카르복스아미드
CA3228162A1 (en)	2021-08-18	2023-02-23	Gilead Sciences, Inc.	Phospholipid compounds and methods of making and using the same
CN121181574A (zh) *	2025-11-24	2025-12-23	重庆汉佩生物科技有限公司	一种头孢维星衍生物和应用以及制备方法
CN121181573A (zh) *	2025-11-24	2025-12-23	重庆汉佩生物科技有限公司	一种含c-3位四氢呋喃头孢菌素衍生物和应用

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GB1385831A (en) *	1972-05-05	1975-03-05	Hoechst Ag	Acylamino-cephem-carboxylic acids and process for their preparation
EP0075805A1 (de) *	1981-09-18	1983-04-06	Kyowa Hakko Kogyo Co., Ltd	Beta-Lactam-Verbindung und eine diese Verbindung enthaltende pharmazeutische Zusammensetzung

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FR2197573A1 (en) *	1972-09-07	1974-03-29	Roussel Uclaf	7-substd-phenylacetamido-cephalosporin derivs - - antibiotics active against streptococci and staphylococci
BE791161A (fr) *	1972-01-03	1973-05-09	Beecham Group Ltd	Procede pour la preparation d'analogues des cephalosporines
BE791160A (fr) *	1972-01-03	1973-05-09	Beecham Group Ltd	Nouveaux cephemes substitues
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ATE171705T1 (de) *	1989-03-30	1998-10-15	Pfizer	Cephalosporine und ihre homologen, verfahren zu ihrer herstellung und pharmazeutische präparate

1991
- 1991-07-16 MY MYPI91001321A patent/MY106399A/en unknown
- 1991-07-22 WO PCT/GB1991/001228 patent/WO1992001696A1/en not_active Ceased
- 1991-07-22 EP EP91913545A patent/EP0540606A1/de not_active Withdrawn
- 1991-07-22 CA CA002359744A patent/CA2359744C/en not_active Expired - Lifetime
- 1991-07-22 AP APAP/P/1991/000305A patent/AP832A/en active
- 1991-07-22 DK DK91913583T patent/DK0540609T3/da active
- 1991-07-22 KR KR1019930700216A patent/KR100189075B1/ko not_active Expired - Lifetime
- 1991-07-22 FI FI930270A patent/FI930270A7/fi unknown
- 1991-07-22 AU AU82224/91A patent/AU648329B2/en not_active Expired
- 1991-07-22 WO PCT/GB1991/001227 patent/WO1992001695A1/en not_active Ceased
- 1991-07-22 NZ NZ239061A patent/NZ239061A/en not_active IP Right Cessation
- 1991-07-22 IE IE256991A patent/IE912569A1/en not_active IP Right Cessation
- 1991-07-22 EP EP91913583A patent/EP0540609B1/de not_active Expired - Lifetime
- 1991-07-22 MX MX9100317A patent/MX9100317A/es unknown
- 1991-07-22 DE DE200612000065 patent/DE122006000065I2/de active Active
- 1991-07-22 JP JP3512368A patent/JP2851428B2/ja not_active Expired - Lifetime
- 1991-07-22 AT AT91913583T patent/ATE185567T1/de active
- 1991-07-22 CZ CS9364A patent/CZ6493A3/cs unknown
- 1991-07-22 CA CA002087967A patent/CA2087967C/en not_active Expired - Lifetime
- 1991-07-22 ES ES91913583T patent/ES2137162T3/es not_active Expired - Lifetime
- 1991-07-22 JP JP3512255A patent/JPH05509089A/ja active Pending
- 1991-07-22 IL IL98909A patent/IL98909A0/xx unknown
- 1991-07-22 HU HU93177A patent/HUT63628A/hu unknown
- 1991-07-22 DE DE69131714T patent/DE69131714T2/de not_active Expired - Lifetime
- 1991-07-23 PT PT98426A patent/PT98426A/pt not_active Application Discontinuation
- 1991-07-23 YU YU129691A patent/YU129691A/sh unknown
- 1991-07-24 CN CN91105783A patent/CN1061046C/zh not_active Expired - Lifetime
1993
- 1993-01-22 NO NO93930226A patent/NO930226L/no unknown
1998
- 1998-11-14 CN CN98122407A patent/CN1111410C/zh not_active Expired - Lifetime
1999
- 1999-11-03 GR GR990402803T patent/GR3031711T3/el unknown
2006
- 2006-11-22 LU LU91290C patent/LU91290I2/fr unknown
- 2006-11-27 NL NL300249C patent/NL300249I2/en unknown

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Also Published As

Publication number	Publication date
LU91290I2 (fr)	2007-01-22
IL98909A0 (en)	1992-07-15
FI930270L (fi)	1993-03-22
IE912569A1 (en)	1992-01-29
CA2359744C (en)	2007-02-13
CN1223859A (zh)	1999-07-28
MY106399A (en)	1995-05-30
CA2087967A1 (en)	1992-01-25
PT98426A (pt)	1992-05-29
ATE185567T1 (de)	1999-10-15
FI930270A0 (fi)	1993-01-22
JP2851428B2 (ja)	1999-01-27
DE69131714D1 (de)	1999-11-18
WO1992001695A1 (en)	1992-02-06
AP9100305A0 (en)	1991-07-31
DE122006000065I2 (de)	2007-09-13
NO930226D0 (no)	1993-01-22
CN1111410C (zh)	2003-06-18
YU129691A (sh)	1994-01-20
CA2359744A1 (en)	1992-02-06
EP0540609A1 (de)	1993-05-12
DE69131714T2 (de)	2000-02-24
NL300249I1 (nl)	2007-02-01
DE122006000065I1 (de)	2007-03-01
GR3031711T3 (en)	2000-02-29
NO930226L (no)	1993-03-23
NL300249I2 (en)	2007-02-01
DK0540609T3 (da)	1999-12-27
CZ6493A3 (en)	1994-04-13
HU9300177D0 (en)	1993-04-28
EP0540606A1 (de)	1993-05-12
JPH05509089A (ja)	1993-12-16
CN1061046C (zh)	2001-01-24
EP0540609B1 (de)	1999-10-13
CN1060469A (zh)	1992-04-22
JPH05509305A (ja)	1993-12-22
NZ239061A (en)	1993-11-25
AU8222491A (en)	1992-02-18
CA2087967C (en)	2002-09-10
MX9100317A (es)	1992-02-28
KR100189075B1 (ko)	1999-06-01
KR930701456A (ko)	1993-06-11
HUT63628A (en)	1993-09-28
ES2137162T3 (es)	1999-12-16
FI930270A7 (fi)	1993-03-22
WO1992001696A1 (en)	1992-02-06
AU648329B2 (en)	1994-04-21

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EP0548186B1 (de)	1997-03-05	Cephalosporin-derivate und deren homologe
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EP0287734A1 (de)	1988-10-26	2-Beta-substituiertes-methyl-penamderivate
US6080855A (en)	2000-06-27	2-isocephem and oxacephem derivatives and use as antibacterial agents
EP0644886A1 (de)	1995-03-29	3.substituierte carbacepheme
EP0416810A2 (de)	1991-03-13	Cephalosporinderivate, Verfahren zu ihrer Herstellung, pharmazeutische Präparate und Zwischenverbindungen
US5602117A (en)	1997-02-11	Cephalosporin compounds
EP0293532A1 (de)	1988-12-07	6- oder 7-beta-[2-[4-(substituiertes)-2,3-Dioxopiperazin-1-yl-carbonylamino]-(substituiertes)acetamido]-Penicillin und Cephalosporin-Derivate
EP0354757A2 (de)	1990-02-14	Cephalosporine und homologe Verbindungen, Verfahren zu ihrer Herstellung und sie enthaltende pharmazeutische Präparate
AP199A (en)	1992-06-30	Novel B-Lactam and a novel class cephalosporins.
EP0308559A2 (de)	1989-03-29	Cephalosporinen, Verfahren zu ihrer Herstellung, sie enthaltende pharmazeutische Präparate und Zwischenverbindungen
EP0689540A1 (de)	1996-01-03	Carbacephalosporine, verfahren zu deren herstellung und anwendung
EP0389178A2 (de)	1990-09-26	Acrylamidopenizillansäure-Derivate
IE904401A1 (en)	1991-06-19	Novel compounds