FI63581C - Foerfarande foer framstaellning av 9-tiodeoxiclavulansyraderivat med beta-laktamasinhibitorverkan - Google Patents
Foerfarande foer framstaellning av 9-tiodeoxiclavulansyraderivat med beta-laktamasinhibitorverkan Download PDFInfo
- Publication number
- FI63581C FI63581C FI770295A FI770295A FI63581C FI 63581 C FI63581 C FI 63581C FI 770295 A FI770295 A FI 770295A FI 770295 A FI770295 A FI 770295A FI 63581 C FI63581 C FI 63581C
- Authority
- FI
- Finland
- Prior art keywords
- solution
- formula
- nitrobenzyl
- salt
- sodium
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- 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
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- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 15
- 159000000000 sodium salts Chemical class 0.000 description 15
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- 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
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- 238000006243 chemical reaction Methods 0.000 description 11
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- 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
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- 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
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- 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
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- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 230000007062 hydrolysis Effects 0.000 description 6
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- 241000191967 Staphylococcus aureus Species 0.000 description 5
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- 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
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- 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
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- 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)
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 (de) | 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 (de) |
| JP (1) | JPS5295689A (de) |
| AR (3) | AR214306A1 (de) |
| AT (1) | AT351675B (de) |
| AU (1) | AU515736B2 (de) |
| BG (1) | BG27751A3 (de) |
| CA (1) | CA1089471A (de) |
| CH (2) | CH637655A5 (de) |
| CS (1) | CS196341B2 (de) |
| DD (1) | DD128196A5 (de) |
| DE (1) | DE2702954A1 (de) |
| DK (1) | DK146940C (de) |
| ES (1) | ES455404A1 (de) |
| FI (1) | FI63581C (de) |
| FR (1) | FR2339616A1 (de) |
| GR (1) | GR62544B (de) |
| HK (1) | HK69883A (de) |
| IE (1) | IE44759B1 (de) |
| IL (1) | IL51267A (de) |
| KE (1) | KE3303A (de) |
| LU (1) | LU76668A1 (de) |
| MX (1) | MX4950E (de) |
| NL (1) | NL7700892A (de) |
| NO (1) | NO770279L (de) |
| NZ (1) | NZ183117A (de) |
| PH (1) | PH13924A (de) |
| PT (1) | PT66071B (de) |
| RO (1) | RO69712A (de) |
| SE (1) | SE441359B (de) |
| SU (1) | SU645583A3 (de) |
| YU (1) | YU10777A (de) |
Families Citing this family (10)
| 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 |
| EP0008899B1 (de) * | 1978-09-05 | 1982-09-15 | Beecham Group Plc | Clavulansäurederivate, ihre Herstellung und sie enthaltende pharmazeutische Zusammensetzungen |
| EP0018203B1 (de) * | 1979-04-21 | 1983-03-02 | Beecham Group Plc | Clavulansäure-Derivate, ihre Herstellung und Verwendung in Arzneimitteln |
| 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 (de) * | 1980-12-09 | 1985-03-20 | Beecham Group Plc | Clavulansäure-Derivate, ihre Herstellung und ihre Verwendung |
| NZ199200A (en) * | 1980-12-23 | 1984-07-31 | Beecham Group Ltd | Clavulanic acid derivatives and pharmaceutical compositions |
| 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)
| 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 IL IL51267A patent/IL51267A/xx unknown
- 1977-01-14 PT PT66071A patent/PT66071B/pt unknown
- 1977-01-17 YU YU00107/77A patent/YU10777A/xx unknown
- 1977-01-17 PH PH19356A patent/PH13924A/en unknown
- 1977-01-18 NZ NZ183117A patent/NZ183117A/xx unknown
- 1977-01-18 GR GR52592A patent/GR62544B/el 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 CH CH94177A patent/CH637655A5/de not_active IP Right Cessation
- 1977-01-26 AR AR266318A patent/AR214306A1/es active
- 1977-01-26 BG BG035265A patent/BG27751A3/xx unknown
- 1977-01-27 ES ES455404A patent/ES455404A1/es not_active Expired
- 1977-01-27 CA CA270,533A patent/CA1089471A/en not_active Expired
- 1977-01-28 DD DD7700197138A patent/DD128196A5/de unknown
- 1977-01-28 DK DK38577A patent/DK146940C/da not_active IP Right Cessation
- 1977-01-28 SU SU772447048A patent/SU645583A3/ru active
- 1977-01-28 FR FR7702402A patent/FR2339616A1/fr active Granted
- 1977-01-28 MX MX775395U patent/MX4950E/es unknown
- 1977-01-28 NL NL7700892A patent/NL7700892A/xx not_active Application Discontinuation
- 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 NO NO770279A patent/NO770279L/no unknown
- 1977-01-28 LU LU76668A patent/LU76668A1/xx unknown
- 1977-01-28 SE SE7700946A patent/SE441359B/xx not_active IP Right Cessation
- 1977-01-28 AU AU21770/77A patent/AU515736B2/en not_active Expired
- 1977-01-28 AT AT53477A patent/AT351675B/de not_active IP Right Cessation
- 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
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: BEECHAM GROUP LIMITED |