FI63581C - Foerfarande foer framstaellning av 9-tiodeoxiclavulansyraderivat med beta-laktamasinhibitorverkan - Google Patents

Foerfarande foer framstaellning av 9-tiodeoxiclavulansyraderivat med beta-laktamasinhibitorverkan Download PDF

Info

Publication number: FI63581C
Authority: FI; Finland
Prior art keywords: solution; formula; nitrobenzyl; salt; sodium
Prior art date: 1976-01-31

Application number

FI770295A

Other languages

English (en)

Finnish (fi)

Other versions

FI770295A (ro

FI63581B (fi

Inventor

Roger John Ponsford

Original Assignee

Beecham Group Ltd

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

1976-01-31

Filing date

1977-01-28

Publication date

1983-07-11

1976-01-31 Priority claimed from GB3892/76A external-priority patent/GB1574906A/en

1977-01-28 Application filed by Beecham Group Ltd filed Critical Beecham Group Ltd

1977-08-01 Publication of FI770295A publication Critical patent/FI770295A/fi

1983-03-31 Application granted granted Critical

1983-03-31 Publication of FI63581B publication Critical patent/FI63581B/fi

1983-07-11 Publication of FI63581C publication Critical patent/FI63581C/fi

Links

150000001875 compounds Chemical class 0.000 claims description 44
-1 clavulanic acid ester Chemical class 0.000 claims description 41
150000002148 esters Chemical class 0.000 claims description 32
150000003839 salts Chemical class 0.000 claims description 31
HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 claims description 27
125000000217 alkyl group Chemical group 0.000 claims description 11
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
239000002253 acid Substances 0.000 claims description 8
238000000034 method Methods 0.000 claims description 6
229910052739 hydrogen Inorganic materials 0.000 claims description 5
239000001257 hydrogen Substances 0.000 claims description 5
238000002360 preparation method Methods 0.000 claims description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
239000003781 beta lactamase inhibitor Substances 0.000 claims description 4
229940126813 beta-lactamase inhibitor Drugs 0.000 claims description 4
230000003647 oxidation Effects 0.000 claims description 4
238000007254 oxidation reaction Methods 0.000 claims description 4
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
229960003324 clavulanic acid Drugs 0.000 claims description 3
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 2
125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 2
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
125000001072 heteroaryl group Chemical group 0.000 claims description 2
239000011968 lewis acid catalyst Substances 0.000 claims description 2
125000006502 nitrobenzyl group Chemical group 0.000 claims description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
125000003831 tetrazolyl group Chemical group 0.000 claims description 2
125000001113 thiadiazolyl group Chemical group 0.000 claims description 2
125000002769 thiazolinyl group Chemical group 0.000 claims description 2
125000001425 triazolyl group Chemical group 0.000 claims description 2
125000003545 alkoxy group Chemical group 0.000 claims 1
238000005886 esterification reaction Methods 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 123
239000000243 solution Substances 0.000 description 83
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 40
239000000203 mixture Substances 0.000 description 39
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
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 37
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 30
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
229940090805 clavulanate Drugs 0.000 description 24
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 21
238000004587 chromatography analysis Methods 0.000 description 20
NKBWMBRPILTCRD-UHFFFAOYSA-N 2-Methylheptanoic acid Chemical compound CCCCCC(C)C(O)=O NKBWMBRPILTCRD-UHFFFAOYSA-N 0.000 description 19
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
239000011734 sodium Substances 0.000 description 18
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 16
239000003921 oil Substances 0.000 description 16
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
229910052708 sodium Inorganic materials 0.000 description 15
235000017557 sodium bicarbonate Nutrition 0.000 description 15
229910000030 sodium bicarbonate Inorganic materials 0.000 description 15
159000000000 sodium salts Chemical class 0.000 description 15
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
239000007787 solid Substances 0.000 description 14
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 13
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
229910002091 carbon monoxide Inorganic materials 0.000 description 13
239000002904 solvent Substances 0.000 description 13
229960000723 ampicillin Drugs 0.000 description 12
AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
238000006243 chemical reaction Methods 0.000 description 11
229910052763 palladium Inorganic materials 0.000 description 11
239000000047 product Substances 0.000 description 11
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
102000006635 beta-lactamase Human genes 0.000 description 10
239000012230 colorless oil Substances 0.000 description 10
DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
238000005984 hydrogenation reaction Methods 0.000 description 9
238000002955 isolation Methods 0.000 description 9
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 9
229930186147 Cephalosporin Natural products 0.000 description 8
108090000204 Dipeptidase 1 Proteins 0.000 description 8
229940124587 cephalosporin Drugs 0.000 description 8
150000001780 cephalosporins Chemical class 0.000 description 8
HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 8
238000001704 evaporation Methods 0.000 description 8
230000008020 evaporation Effects 0.000 description 8
235000019371 penicillin G benzathine Nutrition 0.000 description 8
229940056360 penicillin g Drugs 0.000 description 8
239000000741 silica gel Substances 0.000 description 8
229910002027 silica gel Inorganic materials 0.000 description 8
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 7
229930182555 Penicillin Natural products 0.000 description 7
229910052744 lithium Inorganic materials 0.000 description 7
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 6
239000012267 brine Substances 0.000 description 6
239000003153 chemical reaction reagent Substances 0.000 description 6
230000007062 hydrolysis Effects 0.000 description 6
238000006460 hydrolysis reaction Methods 0.000 description 6
208000015181 infectious disease Diseases 0.000 description 6
229940049954 penicillin Drugs 0.000 description 6
241000191967 Staphylococcus aureus Species 0.000 description 5
229960003022 amoxicillin Drugs 0.000 description 5
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical group FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 5
239000006260 foam Substances 0.000 description 5
230000005764 inhibitory process Effects 0.000 description 5
229910003002 lithium salt Inorganic materials 0.000 description 5
159000000002 lithium salts Chemical class 0.000 description 5
LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 5
150000003568 thioethers Chemical class 0.000 description 5
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
LULAYUGMBFYYEX-UHFFFAOYSA-N 3-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 4
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 4
LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 4
239000002585 base Substances 0.000 description 4
AZUFHGGGPUUXKI-FLFDDASRSA-N benzyl (2r,3z,5r)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound O=C([C@@H]1N2C(=O)C[C@H]2O\C1=C/CO)OCC1=CC=CC=C1 AZUFHGGGPUUXKI-FLFDDASRSA-N 0.000 description 4
239000003814 drug Substances 0.000 description 4
239000003112 inhibitor Substances 0.000 description 4
229910052943 magnesium sulfate Inorganic materials 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
229910015900 BF3 Inorganic materials 0.000 description 3
GNWUOVJNSFPWDD-XMZRARIVSA-M Cefoxitin sodium Chemical compound [Na+].N([C@]1(OC)C(N2C(=C(COC(N)=O)CS[C@@H]21)C([O-])=O)=O)C(=O)CC1=CC=CS1 GNWUOVJNSFPWDD-XMZRARIVSA-M 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-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
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
238000002835 absorbance Methods 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
230000000844 anti-bacterial effect Effects 0.000 description 3
UENWRTRMUIOCKN-UHFFFAOYSA-N benzyl thiol Chemical compound SCC1=CC=CC=C1 UENWRTRMUIOCKN-UHFFFAOYSA-N 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
229960002682 cefoxitin Drugs 0.000 description 3
FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 3
CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
230000002401 inhibitory effect Effects 0.000 description 3
238000004949 mass spectrometry Methods 0.000 description 3
239000007800 oxidant agent Substances 0.000 description 3
239000002243 precursor Substances 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
239000000725 suspension Substances 0.000 description 3
229940124597 therapeutic agent Drugs 0.000 description 3
YXIWHUQXZSMYRE-UHFFFAOYSA-N 1,3-benzothiazole-2-thiol Chemical compound C1=CC=C2SC(S)=NC2=C1 YXIWHUQXZSMYRE-UHFFFAOYSA-N 0.000 description 2
108020004256 Beta-lactamase Proteins 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
238000010521 absorption reaction Methods 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
FPPNZSSZRUTDAP-UWFZAAFLSA-N carbenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C(C(O)=O)C1=CC=CC=C1 FPPNZSSZRUTDAP-UWFZAAFLSA-N 0.000 description 2
229960003669 carbenicillin Drugs 0.000 description 2
238000010790 dilution Methods 0.000 description 2
239000012895 dilution Substances 0.000 description 2
239000012153 distilled water Substances 0.000 description 2
125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 description 2
238000001914 filtration Methods 0.000 description 2
239000012442 inert solvent Substances 0.000 description 2
238000001802 infusion Methods 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
150000002500 ions Chemical class 0.000 description 2
239000010410 layer Substances 0.000 description 2
230000007246 mechanism Effects 0.000 description 2
150000004702 methyl esters Chemical class 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
229910001415 sodium ion Inorganic materials 0.000 description 2
238000003756 stirring Methods 0.000 description 2
230000002195 synergetic effect Effects 0.000 description 2
229960004659 ticarcillin Drugs 0.000 description 2
125000003944 tolyl group Chemical group 0.000 description 2
238000001665 trituration Methods 0.000 description 2
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
WGJCBBASTRWVJL-UHFFFAOYSA-N 1,3-thiazolidine-2-thione Chemical compound SC1=NCCS1 WGJCBBASTRWVJL-UHFFFAOYSA-N 0.000 description 1
XOHZHMUQBFJTNH-UHFFFAOYSA-N 1-methyl-2h-tetrazole-5-thione Chemical compound CN1N=NN=C1S XOHZHMUQBFJTNH-UHFFFAOYSA-N 0.000 description 1
OMAFFHIGWTVZOH-UHFFFAOYSA-N 1-methyltetrazole Chemical compound CN1C=NN=N1 OMAFFHIGWTVZOH-UHFFFAOYSA-N 0.000 description 1
ULQQGOGMQRGFFR-UHFFFAOYSA-N 2-chlorobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC=CC=C1Cl ULQQGOGMQRGFFR-UHFFFAOYSA-N 0.000 description 1
RQSCFNPNNLWQBJ-UHFFFAOYSA-N 2-methyl-1,3,4-thiadiazole Chemical compound CC1=NN=CS1 RQSCFNPNNLWQBJ-UHFFFAOYSA-N 0.000 description 1
FPFSGDXIBUDDKZ-UHFFFAOYSA-N 3-decyl-2-hydroxycyclopent-2-en-1-one Chemical compound CCCCCCCCCCC1=C(O)C(=O)CC1 FPFSGDXIBUDDKZ-UHFFFAOYSA-N 0.000 description 1
IUSDGVJFDZRIBR-UHFFFAOYSA-N 3-phenylpropane-1-thiol Chemical compound SCCCC1=CC=CC=C1 IUSDGVJFDZRIBR-UHFFFAOYSA-N 0.000 description 1
NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
PCVRSXXPGXRVEZ-UHFFFAOYSA-N 9-(chloromethyl)anthracene Chemical compound C1=CC=C2C(CCl)=C(C=CC=C3)C3=CC2=C1 PCVRSXXPGXRVEZ-UHFFFAOYSA-N 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
208000031462 Bovine Mastitis Diseases 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
241000588923 Citrobacter Species 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
241000588914 Enterobacter Species 0.000 description 1
241000588724 Escherichia coli Species 0.000 description 1
241000588915 Klebsiella aerogenes Species 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
229930195708 Penicillin V Natural products 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
241000588770 Proteus mirabilis Species 0.000 description 1
241000589516 Pseudomonas Species 0.000 description 1
241000589517 Pseudomonas aeruginosa Species 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical group [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 1
101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
229910001413 alkali metal ion Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
229910001420 alkaline earth metal ion Inorganic materials 0.000 description 1
150000003973 alkyl amines Chemical class 0.000 description 1
229960004920 amoxicillin trihydrate Drugs 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
230000001580 bacterial effect Effects 0.000 description 1
239000003899 bactericide agent Substances 0.000 description 1
239000003782 beta lactam antibiotic agent Substances 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
HRQGCQVOJVTVLU-UHFFFAOYSA-N bis(chloromethyl) ether Chemical compound ClCOCCl HRQGCQVOJVTVLU-UHFFFAOYSA-N 0.000 description 1
229910052796 boron Inorganic materials 0.000 description 1
239000000872 buffer Substances 0.000 description 1
239000006172 buffering agent Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000011575 calcium Substances 0.000 description 1
239000002775 capsule Substances 0.000 description 1
FUBBGQLTSCSAON-PBFPGSCMSA-N cefaloglycin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)COC(=O)C)C(O)=O)=CC=CC=C1 FUBBGQLTSCSAON-PBFPGSCMSA-N 0.000 description 1
229950004030 cefaloglycin Drugs 0.000 description 1
CZTQZXZIADLWOZ-CRAIPNDOSA-N cefaloridine Chemical compound O=C([C@@H](NC(=O)CC=1SC=CC=1)[C@H]1SC2)N1C(C(=O)[O-])=C2C[N+]1=CC=CC=C1 CZTQZXZIADLWOZ-CRAIPNDOSA-N 0.000 description 1
229960003866 cefaloridine Drugs 0.000 description 1
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 1
229960001139 cefazolin Drugs 0.000 description 1
MLYYVTUWGNIJIB-BXKDBHETSA-N cefazolin Chemical compound S1C(C)=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CN3N=NN=C3)[C@H]2SC1 MLYYVTUWGNIJIB-BXKDBHETSA-N 0.000 description 1
WZOZEZRFJCJXNZ-ZBFHGGJFSA-N cefoxitin Chemical compound N([C@]1(OC)C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)CC1=CC=CS1 WZOZEZRFJCJXNZ-ZBFHGGJFSA-N 0.000 description 1
ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 description 1
229940106164 cephalexin Drugs 0.000 description 1
229920001429 chelating resin Polymers 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
230000000052 comparative effect Effects 0.000 description 1
229940125898 compound 5 Drugs 0.000 description 1
238000001816 cooling Methods 0.000 description 1
229920001577 copolymer Polymers 0.000 description 1
101150084411 crn1 gene Proteins 0.000 description 1
239000012043 crude product Substances 0.000 description 1
CMKBCTPCXZNQKX-UHFFFAOYSA-N cyclohexanethiol Chemical compound SC1CCCCC1 CMKBCTPCXZNQKX-UHFFFAOYSA-N 0.000 description 1
125000005265 dialkylamine group Chemical group 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
229910001873 dinitrogen Inorganic materials 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
MYRTYDVEIRVNKP-UHFFFAOYSA-N divinylbenzene Substances C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 1
229940116441 divinylbenzene Drugs 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
239000000975 dye Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
238000010828 elution Methods 0.000 description 1
239000002702 enteric coating Substances 0.000 description 1
238000009505 enteric coating Methods 0.000 description 1
RPBAFSBGYDKNRG-NJBDSQKTSA-N epicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CCC=CC1 RPBAFSBGYDKNRG-NJBDSQKTSA-N 0.000 description 1
229960002457 epicillin Drugs 0.000 description 1
PVBRSNZAOAJRKO-UHFFFAOYSA-N ethyl 2-sulfanylacetate Chemical compound CCOC(=O)CS PVBRSNZAOAJRKO-UHFFFAOYSA-N 0.000 description 1
IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
DXVUYOAEDJXBPY-NFFDBFGFSA-N hetacillin Chemical compound C1([C@@H]2C(=O)N(C(N2)(C)C)[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 DXVUYOAEDJXBPY-NFFDBFGFSA-N 0.000 description 1
229960003884 hetacillin Drugs 0.000 description 1
150000002431 hydrogen Chemical class 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
230000002779 inactivation Effects 0.000 description 1
238000011534 incubation Methods 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
239000002054 inoculum Substances 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
229910052808 lithium carbonate Inorganic materials 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
239000000463 material Substances 0.000 description 1
FZECHKJQHUVANE-MCYUEQNJSA-N metampicillin Chemical compound C1([C@@H](N=C)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 FZECHKJQHUVANE-MCYUEQNJSA-N 0.000 description 1
229960003806 metampicillin Drugs 0.000 description 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
LGWAZBSQZYQLBB-UHFFFAOYSA-N methyl 3-(2-benzylsulfonylethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound COC(=O)C1N(C(C2)=O)C2OC1=CCS(=O)(=O)CC1=CC=CC=C1 LGWAZBSQZYQLBB-UHFFFAOYSA-N 0.000 description 1
PSLHYONYYRPVBE-UHFFFAOYSA-N methyl 7-oxo-3-(2-thiophen-2-ylethylidene)-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound COC(=O)C1N(C(C2)=O)C2OC1=CCC1=CC=CS1 PSLHYONYYRPVBE-UHFFFAOYSA-N 0.000 description 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
229960003085 meticillin Drugs 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
239000002674 ointment Substances 0.000 description 1
150000004967 organic peroxy acids Chemical class 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
229940056367 penicillin v Drugs 0.000 description 1
150000002960 penicillins Chemical class 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
229940127557 pharmaceutical product Drugs 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
BPLBGHOLXOTWMN-MBNYWOFBSA-N phenoxymethylpenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)COC1=CC=CC=C1 BPLBGHOLXOTWMN-MBNYWOFBSA-N 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
125000005633 phthalidyl group Chemical group 0.000 description 1
239000004033 plastic Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
229910001414 potassium ion Inorganic materials 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
229960003672 propicillin Drugs 0.000 description 1
HOCWPKXKMNXINF-XQERAMJGSA-N propicillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C(CC)OC1=CC=CC=C1 HOCWPKXKMNXINF-XQERAMJGSA-N 0.000 description 1
229920005989 resin Polymers 0.000 description 1
239000011347 resin Substances 0.000 description 1
210000002345 respiratory system Anatomy 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
WOGMLDNCNBLDCA-JSYANWSFSA-M sodium;(2r,3z,5r)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound [Na+].[O-]C(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 WOGMLDNCNBLDCA-JSYANWSFSA-M 0.000 description 1
210000004872 soft tissue Anatomy 0.000 description 1
239000012265 solid product Substances 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000000758 substrate Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000012085 test solution Substances 0.000 description 1
OHKOGUYZJXTSFX-KZFFXBSXSA-N ticarcillin Chemical compound C=1([C@@H](C(O)=O)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)C=CSC=1 OHKOGUYZJXTSFX-KZFFXBSXSA-N 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
229910052723 transition metal Inorganic materials 0.000 description 1
150000003624 transition metals Chemical class 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
150000003852 triazoles Chemical class 0.000 description 1
210000001635 urinary tract Anatomy 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1
239000002132 β-lactam antibiotic Substances 0.000 description 1
229940124586 β-lactam antibiotics Drugs 0.000 description 1
150000003952 β-lactams Chemical class 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
- A61K31/545—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, cefaclor, or cephalexine
- 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
- C07D503/00—Heterocyclic compounds containing 4-oxa-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. oxapenicillins, clavulanic acid derivatives; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Epidemiology (AREA)
Oncology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Communicable Diseases (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Cephalosporin Compounds (AREA)

FI770295A 1976-01-31 1977-01-28 Foerfarande foer framstaellning av 9-tiodeoxiclavulansyraderivat med beta-laktamasinhibitorverkan FI63581C (fi)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
GB3892/76A GB1574906A (en)	1976-01-31	1976-01-31	Therapeutic compounds containing - lactams
GB389276		1976-01-31
GB1900276		1976-05-08
GB1900276		1976-05-08

Publications (3)

Publication Number	Publication Date
FI770295A FI770295A (ro)	1977-08-01
FI63581B FI63581B (fi)	1983-03-31
FI63581C true FI63581C (fi)	1983-07-11

Family

ID=26238678

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
FI770295A FI63581C (fi)	1976-01-31	1977-01-28	Foerfarande foer framstaellning av 9-tiodeoxiclavulansyraderivat med beta-laktamasinhibitorverkan

Country Status (31)

Country	Link
US (2)	US4428958A (ro)
JP (1)	JPS5295689A (ro)
AR (3)	AR214306A1 (ro)
AT (1)	AT351675B (ro)
AU (1)	AU515736B2 (ro)
BG (1)	BG27751A3 (ro)
CA (1)	CA1089471A (ro)
CH (2)	CH637655A5 (ro)
CS (1)	CS196341B2 (ro)
DD (1)	DD128196A5 (ro)
DE (1)	DE2702954A1 (ro)
DK (1)	DK146940C (ro)
ES (1)	ES455404A1 (ro)
FI (1)	FI63581C (ro)
FR (1)	FR2339616A1 (ro)
GR (1)	GR62544B (ro)
HK (1)	HK69883A (ro)
IE (1)	IE44759B1 (ro)
IL (1)	IL51267A (ro)
KE (1)	KE3303A (ro)
LU (1)	LU76668A1 (ro)
MX (1)	MX4950E (ro)
NL (1)	NL7700892A (ro)
NO (1)	NO770279L (ro)
NZ (1)	NZ183117A (ro)
PH (1)	PH13924A (ro)
PT (1)	PT66071B (ro)
RO (1)	RO69712A (ro)
SE (1)	SE441359B (ro)
SU (1)	SU645583A3 (ro)
YU (1)	YU10777A (ro)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1582884A (en) *	1977-05-19	1981-01-14	Beecham Group Ltd	Clavulanic acid derivatives their preparation and use
GB2004541B (en) *	1977-09-16	1982-05-12	Beecham Group Ltd	Ethers of clavulanic acid a process for their preparation and pharmaceutical compositions containing them
ATE1550T1 (de) *	1978-09-05	1982-09-15	Beecham Group Plc	Clavulansaeurederivate, ihre herstellung und sie enthaltende pharmazeutische zusammensetzungen.
EP0018203B1 (en) *	1979-04-21	1983-03-02	Beecham Group Plc	Clavulanic acid derivatives, their preparation and use in pharmaceutical compositions
NZ193687A (en) *	1979-05-17	1982-12-21	Beecham Group Ltd	Clavulanic acid derivatives and pharmaceutical compositions
ZA804670B (en) *	1979-08-03	1981-07-29	Beecham Group Ltd	Derivatives of clavulanic acid, a process for their preparation and their use
EP0053893B1 (en) *	1980-12-09	1985-03-20	Beecham Group Plc	Derivatives of clavulanic acid, their preparation and their use
US4562182A (en) *	1980-12-23	1985-12-31	Beecham Group P.L.C.	Compounds containing beta-lactams
GB9518917D0 (en) *	1995-09-15	1995-11-15	Smithkline Beecham Plc	Compounds
US5958462A (en) *	1997-05-23	1999-09-28	Mclean; Linsey	Therapeutic bath salts and method of use

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4039673A (en)	1973-10-30	1977-08-02	Bayer Aktiengesellschaft	Penicillins and cephalosporins and their production
US3983113A (en)	1975-08-15	1976-09-28	Syntex (U.S.A.) Inc.	Cephalosporin type antibacterials

1977
- 1977-01-14 PT PT66071A patent/PT66071B/pt unknown
- 1977-01-14 IL IL51267A patent/IL51267A/xx unknown
- 1977-01-17 PH PH19356A patent/PH13924A/en unknown
- 1977-01-17 YU YU00107/77A patent/YU10777A/xx unknown
- 1977-01-18 GR GR52592A patent/GR62544B/el unknown
- 1977-01-18 NZ NZ183117A patent/NZ183117A/xx unknown
- 1977-01-20 CS CS77387A patent/CS196341B2/cs unknown
- 1977-01-24 US US05/761,712 patent/US4428958A/en not_active Expired - Lifetime
- 1977-01-25 DE DE19772702954 patent/DE2702954A1/de not_active Withdrawn
- 1977-01-26 AR AR266318A patent/AR214306A1/es active
- 1977-01-26 CH CH94177A patent/CH637655A5/de not_active IP Right Cessation
- 1977-01-26 BG BG035265A patent/BG27751A3/xx unknown
- 1977-01-27 CA CA270,533A patent/CA1089471A/en not_active Expired
- 1977-01-27 ES ES455404A patent/ES455404A1/es not_active Expired
- 1977-01-28 SU SU772447048A patent/SU645583A3/ru active
- 1977-01-28 AU AU21770/77A patent/AU515736B2/en not_active Expired
- 1977-01-28 FR FR7702402A patent/FR2339616A1/fr active Granted
- 1977-01-28 MX MX775395U patent/MX4950E/es unknown
- 1977-01-28 FI FI770295A patent/FI63581C/fi not_active IP Right Cessation
- 1977-01-28 IE IE182/77A patent/IE44759B1/en unknown
- 1977-01-28 LU LU76668A patent/LU76668A1/xx unknown
- 1977-01-28 NO NO770279A patent/NO770279L/no unknown
- 1977-01-28 SE SE7700946A patent/SE441359B/xx not_active IP Right Cessation
- 1977-01-28 AT AT53477A patent/AT351675B/de not_active IP Right Cessation
- 1977-01-28 DK DK38577A patent/DK146940C/da not_active IP Right Cessation
- 1977-01-28 DD DD7700197138A patent/DD128196A5/xx unknown
- 1977-01-28 NL NL7700892A patent/NL7700892A/xx not_active Application Discontinuation
- 1977-01-29 JP JP917077A patent/JPS5295689A/ja active Granted
- 1977-01-31 RO RO197789185A patent/RO69712A/ro unknown
- 1977-11-14 AR AR269972A patent/AR216925A1/es active
1978
- 1978-11-07 AR AR274370A patent/AR216555A1/es active
1982
- 1982-08-30 US US06/412,591 patent/US4505894A/en not_active Expired - Fee Related
- 1982-12-16 CH CH734282A patent/CH638529A5/de not_active IP Right Cessation
1983
- 1983-07-14 KE KE3303A patent/KE3303A/xx unknown
- 1983-12-15 HK HK698/83A patent/HK69883A/xx unknown

Also Published As

Publication number	Publication date
MX4950E (es)	1983-01-12
SE7700946L (sv)	1977-08-01
DD128196A5 (de)	1977-11-02
CA1089471A (en)	1980-11-11
ES455404A1 (es)	1978-05-01
US4428958A (en)	1984-01-31
FR2339616A1 (fr)	1977-08-26
NL7700892A (nl)	1977-08-02
SE441359B (sv)	1985-09-30
DK146940B (da)	1984-02-20
JPS613349B2 (ro)	1986-01-31
IE44759B1 (en)	1982-03-24
IL51267A0 (en)	1977-03-31
BG27751A3 (en)	1979-12-12
CH638529A5 (de)	1983-09-30
DK146940C (da)	1984-07-30
PH13924A (en)	1980-11-04
NO770279L (no)	1977-08-02
AU2177077A (en)	1978-08-03
JPS5295689A (en)	1977-08-11
AU515736B2 (en)	1981-04-30
IL51267A (en)	1979-12-30
YU10777A (en)	1982-06-30
IE44759L (en)	1977-07-31
US4505894A (en)	1985-03-19
PT66071A (en)	1977-02-01
RO69712A (fr)	1980-07-15
FR2339616B1 (ro)	1980-04-11
ATA53477A (de)	1979-01-15
FI770295A (ro)	1977-08-01
HK69883A (en)	1983-12-23
DE2702954A1 (de)	1977-08-04
CH637655A5 (de)	1983-08-15
AT351675B (de)	1979-08-10
AR214306A1 (es)	1979-05-31
DK38577A (da)	1977-08-01
FI63581B (fi)	1983-03-31
AR216925A1 (es)	1980-02-15
GR62544B (en)	1979-05-07
NZ183117A (en)	1979-10-25
AR216555A1 (es)	1979-12-28
PT66071B (en)	1978-06-23
LU76668A1 (ro)	1977-06-28
KE3303A (en)	1983-08-05
SU645583A3 (ru)	1979-01-30
CS196341B2 (en)	1980-03-31

Legal Events

Date	Code	Title	Description
2004-08-31	MM	Patent lapsed	Owner name: BEECHAM GROUP LIMITED

Publication	Publication Date	Title
US4201782A (en)	1980-05-06	Thiadiazolyl cephalosporin analogs
FI63581C (fi)	1983-07-11	Foerfarande foer framstaellning av 9-tiodeoxiclavulansyraderivat med beta-laktamasinhibitorverkan
SK126696A3 (en)	1997-04-09	Cephalosporin antibiotics and antibacterial agents containing them
FI82471C (fi)	1991-03-11	Foerfarande foer framstaellning av farmakologiskt aktiva 6-metylenpenemderivater.
US4447422A (en)	1984-05-08	Penicillins and compositions containing them
US4231928A (en)	1980-11-04	Antibacterial agents
FI89490C (fi)	1993-10-11	Foerfarande foer framstaellning av 2-metoximetyl-penemderivat
EP0025857A1 (en)	1981-04-01	Organic sulfoxides having a latent allyl group, process for preparing the same and pharmaceutical antibacterial composition comprising the same
US4215128A (en)	1980-07-29	Clavulanic acid derivatives their preparation and use
US4342758A (en)	1982-08-03	Allylsulfoxide enzyme inhibitors
AU760249B2 (en)	2003-05-08	Novel c-2 s/o- and s/n formaldehyde acetal derivatives of carbapenem-3-carboxylic acids and their use as antibiotics and beta-lactamase inhibitors
DE3424780A1 (de)	1985-01-17	In 7ss-stellung durch eine carbonamidogruppe, welche einen eine oxogruppe aufweisenden gesaettigten heterocyclischen ring enthaelt, substituierte 3-cephem-4-carbonsaeure-derivate
US4438036A (en)	1984-03-20	β-Lactam antibiotics their preparation and their use
GB1574906A (en)	1980-09-10	Therapeutic compounds containing - lactams
FI85272B (fi)	1991-12-13	Analogifoerfarande foer framstaellning av terapeutiskt anvaendbara 6-(1-acyl-1-hydroximetyl) penicillansyraderivat.
EP0018203B1 (en)	1983-03-02	Clavulanic acid derivatives, their preparation and use in pharmaceutical compositions
US4275067A (en)	1981-06-23	Decarboxyclavulanic acid thio ethers, their preparation and use
FI81584B (fi)	1990-07-31	Foerfarande foer framstaellning av antibakteriella 6-alfa-hydroxietyl-2-substituerad-2-penem-3-karboxylsyror.
US4372962A (en)	1983-02-08	Clavulanic acid derivatives their preparation and use
US4661480A (en)	1987-04-28	Formamido oxacephems
KR810001262B1 (ko)	1981-10-08	β-락탐함유 화합물의 제조방법
FI58332C (fi)	1981-01-12	Foerfarande foer framstaellning av estrar av klavulansyra
EP0086590A1 (en)	1983-08-24	Antibacterial agents, their preparation and use