CH634073A5 - 1,1-Dioxides of penicillanic acid and its esters which are useful as beta-lactamase inhibitors - Google Patents
1,1-Dioxides of penicillanic acid and its esters which are useful as beta-lactamase inhibitors Download PDFInfo
- Publication number
- CH634073A5 CH634073A5 CH618078A CH618078A CH634073A5 CH 634073 A5 CH634073 A5 CH 634073A5 CH 618078 A CH618078 A CH 618078A CH 618078 A CH618078 A CH 618078A CH 634073 A5 CH634073 A5 CH 634073A5
- Authority
- CH
- Switzerland
- Prior art keywords
- penicillanate
- dioxide
- oxide
- acid
- penicillanic acid
- Prior art date
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- RBKMMJSQKNKNEV-RITPCOANSA-N penicillanic acid Chemical compound OC(=O)[C@H]1C(C)(C)S[C@@H]2CC(=O)N21 RBKMMJSQKNKNEV-RITPCOANSA-N 0.000 title claims description 90
- 150000002148 esters Chemical class 0.000 title description 31
- 239000003781 beta lactamase inhibitor Substances 0.000 title description 3
- 229940126813 beta-lactamase inhibitor Drugs 0.000 title description 3
- -1 3-phthalidyl Chemical group 0.000 claims description 130
- 150000001875 compounds Chemical class 0.000 claims description 106
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 30
- 238000000034 method Methods 0.000 claims description 25
- 125000004432 carbon atom Chemical group C* 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 13
- 230000003647 oxidation Effects 0.000 claims description 12
- 238000007254 oxidation reaction Methods 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 239000011734 sodium Substances 0.000 claims description 5
- 229910052708 sodium Inorganic materials 0.000 claims description 5
- 150000003457 sulfones Chemical class 0.000 claims description 4
- 150000003462 sulfoxides Chemical class 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims 1
- 230000001131 transforming effect Effects 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 207
- 239000000203 mixture Substances 0.000 description 57
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 57
- 239000000243 solution Substances 0.000 description 47
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 40
- 239000000047 product Substances 0.000 description 40
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 38
- 238000001727 in vivo Methods 0.000 description 29
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- 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 27
- 230000009102 absorption Effects 0.000 description 26
- 238000010521 absorption reaction Methods 0.000 description 26
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 25
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- 239000002904 solvent Substances 0.000 description 23
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 21
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 21
- 239000002132 β-lactam antibiotic Substances 0.000 description 21
- 229940124586 β-lactam antibiotics Drugs 0.000 description 21
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 20
- 239000012071 phase Substances 0.000 description 19
- FKENQMMABCRJMK-RITPCOANSA-N sulbactam Chemical compound O=S1(=O)C(C)(C)[C@H](C(O)=O)N2C(=O)C[C@H]21 FKENQMMABCRJMK-RITPCOANSA-N 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- OSORMYZMWHVFOZ-UHFFFAOYSA-N phenethyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCCC1=CC=CC=C1 OSORMYZMWHVFOZ-UHFFFAOYSA-N 0.000 description 18
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 17
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 17
- 230000000844 anti-bacterial effect Effects 0.000 description 17
- 239000002253 acid Substances 0.000 description 16
- 244000005700 microbiome Species 0.000 description 16
- 229930182555 Penicillin Natural products 0.000 description 15
- 125000006239 protecting group Chemical group 0.000 description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 14
- 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 13
- 229960000723 ampicillin Drugs 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- 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 13
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical compound O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 description 12
- 239000008346 aqueous phase Substances 0.000 description 11
- 238000001704 evaporation Methods 0.000 description 11
- 230000008020 evaporation Effects 0.000 description 11
- 229910052938 sodium sulfate Inorganic materials 0.000 description 11
- 235000011152 sodium sulphate Nutrition 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- 239000001257 hydrogen Substances 0.000 description 10
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 10
- 108020004256 Beta-lactamase Proteins 0.000 description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000003242 anti bacterial agent Substances 0.000 description 9
- 102000006635 beta-lactamase Human genes 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 9
- 229940049954 penicillin Drugs 0.000 description 9
- 229940056360 penicillin g Drugs 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- 101150041968 CDC13 gene Proteins 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- 238000007796 conventional method Methods 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 150000004820 halides Chemical class 0.000 description 8
- 229930186147 Cephalosporin Natural products 0.000 description 7
- 241000606768 Haemophilus influenzae Species 0.000 description 7
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 7
- 241000191967 Staphylococcus aureus Species 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 229960003669 carbenicillin Drugs 0.000 description 7
- 229940124587 cephalosporin Drugs 0.000 description 7
- 150000001780 cephalosporins Chemical class 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 241000606124 Bacteroides fragilis Species 0.000 description 6
- 241000588747 Klebsiella pneumoniae Species 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- 230000003115 biocidal effect Effects 0.000 description 6
- 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 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
- 229960001139 cefazolin Drugs 0.000 description 6
- 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 6
- 238000007256 debromination reaction Methods 0.000 description 6
- 238000002329 infrared spectrum Methods 0.000 description 6
- 150000002960 penicillins Chemical class 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 150000003254 radicals Chemical class 0.000 description 6
- 150000003952 β-lactams Chemical group 0.000 description 6
- 241000282412 Homo Species 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 239000012298 atmosphere Substances 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 229940047650 haemophilus influenzae Drugs 0.000 description 5
- 239000007800 oxidant agent Substances 0.000 description 5
- 238000007911 parenteral administration Methods 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- 125000005846 1-(alkanoyloxy)ethyl group Chemical group 0.000 description 4
- CLMSHAWYULIVFQ-UHFFFAOYSA-N 3-bromo-3h-2-benzofuran-1-one Chemical compound C1=CC=C2C(Br)OC(=O)C2=C1 CLMSHAWYULIVFQ-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 125000002619 bicyclic group Chemical group 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- YGBFLZPYDUKSPT-MRVPVSSYSA-N cephalosporanic acid Chemical class S1CC(COC(=O)C)=C(C(O)=O)N2C(=O)C[C@H]21 YGBFLZPYDUKSPT-MRVPVSSYSA-N 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 230000032050 esterification Effects 0.000 description 4
- 238000005886 esterification reaction Methods 0.000 description 4
- 229960003750 ethyl chloride Drugs 0.000 description 4
- 238000007327 hydrogenolysis reaction Methods 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 238000007912 intraperitoneal administration Methods 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 230000001590 oxidative effect Effects 0.000 description 4
- 239000012286 potassium permanganate Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 238000007738 vacuum evaporation Methods 0.000 description 4
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 3
- VOLRSQPSJGXRNJ-UHFFFAOYSA-N 4-nitrobenzyl bromide Chemical compound [O-][N+](=O)C1=CC=C(CBr)C=C1 VOLRSQPSJGXRNJ-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 208000035143 Bacterial infection Diseases 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 229930195708 Penicillin V Natural products 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 208000022362 bacterial infectious disease Diseases 0.000 description 3
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 150000004678 hydrides Chemical class 0.000 description 3
- 150000004679 hydroxides Chemical class 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 150000004967 organic peroxy acids Chemical class 0.000 description 3
- 235000019371 penicillin G benzathine Nutrition 0.000 description 3
- 229940056367 penicillin v Drugs 0.000 description 3
- 150000004965 peroxy acids Chemical class 0.000 description 3
- 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 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- VYPDUQYOLCLEGS-UHFFFAOYSA-M sodium;2-ethylhexanoate Chemical compound [Na+].CCCCC(CC)C([O-])=O VYPDUQYOLCLEGS-UHFFFAOYSA-M 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- RDMHXWZYVFGYSF-LNTINUHCSA-N (z)-4-hydroxypent-3-en-2-one;manganese Chemical compound [Mn].C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O RDMHXWZYVFGYSF-LNTINUHCSA-N 0.000 description 2
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 2
- 125000005848 1-(alkoxycarbonyloxy)ethyl group Chemical group 0.000 description 2
- 125000005847 1-methyl-1-(alkanoyloxy)-ethyl group Chemical group 0.000 description 2
- 125000005849 1-methyl-1-(alkoxycarbonyloxy)ethyl group Chemical group 0.000 description 2
- ODQLAECNMKXOBI-UHFFFAOYSA-N 2-bromo-2h-furan-5-one Chemical compound BrC1OC(=O)C=C1 ODQLAECNMKXOBI-UHFFFAOYSA-N 0.000 description 2
- YNJSNEKCXVFDKW-UHFFFAOYSA-N 3-(5-amino-1h-indol-3-yl)-2-azaniumylpropanoate Chemical compound C1=C(N)C=C2C(CC(N)C(O)=O)=CNC2=C1 YNJSNEKCXVFDKW-UHFFFAOYSA-N 0.000 description 2
- SRXYQTZEGZGPCA-UHFFFAOYSA-N 5-bromooxolan-2-one Chemical compound BrC1CCC(=O)O1 SRXYQTZEGZGPCA-UHFFFAOYSA-N 0.000 description 2
- WYUIPMUZDFHKMP-UHFFFAOYSA-N 5-chloro-1,3-dihydropyrrolo[3,2-b]pyridin-2-one Chemical compound ClC1=CC=C2NC(=O)CC2=N1 WYUIPMUZDFHKMP-UHFFFAOYSA-N 0.000 description 2
- NVIAYEIXYQCDAN-CLZZGJSISA-N 7beta-aminodeacetoxycephalosporanic acid Chemical compound S1CC(C)=C(C(O)=O)N2C(=O)[C@@H](N)[C@@H]12 NVIAYEIXYQCDAN-CLZZGJSISA-N 0.000 description 2
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- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
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- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 239000005909 Kieselgur Substances 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 2
- 241000588652 Neisseria gonorrhoeae Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 125000004423 acyloxy group Chemical group 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 125000005206 alkoxycarbonyloxymethyl group Chemical group 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 125000003460 beta-lactamyl group Chemical group 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
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- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
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- 239000011591 potassium Substances 0.000 description 1
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- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
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- 239000000843 powder Substances 0.000 description 1
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- 150000003141 primary amines Chemical class 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
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- 230000009257 reactivity Effects 0.000 description 1
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- 230000007017 scission Effects 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000010802 sludge Substances 0.000 description 1
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 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
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- HWEXKRHYVOGVDA-UHFFFAOYSA-M sodium;3-trimethylsilylpropane-1-sulfonate Chemical compound [Na+].C[Si](C)(C)CCCS([O-])(=O)=O HWEXKRHYVOGVDA-UHFFFAOYSA-M 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
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- 239000008174 sterile solution Substances 0.000 description 1
- 229960005256 sulbactam Drugs 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- NRTLTGGGUQIRRT-UHFFFAOYSA-N triethylazanium;bromide Chemical compound [Br-].CC[NH+](CC)CC NRTLTGGGUQIRRT-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
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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
- A61K31/54—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic 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; 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
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- 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
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
-
- 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)
- Health & Medical 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)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US80432077A | 1977-06-07 | 1977-06-07 | |
| US87938178A | 1978-02-21 | 1978-02-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH634073A5 true CH634073A5 (en) | 1983-01-14 |
Family
ID=27122691
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH618078A CH634073A5 (en) | 1977-06-07 | 1978-06-06 | 1,1-Dioxides of penicillanic acid and its esters which are useful as beta-lactamase inhibitors |
Country Status (35)
| Country | Link |
|---|---|
| AR (1) | AR224111A1 (en, 2012) |
| AT (2) | AT360649B (en, 2012) |
| AU (1) | AU513636B2 (en, 2012) |
| BE (1) | BE867859A (en, 2012) |
| BG (2) | BG34615A3 (en, 2012) |
| CH (1) | CH634073A5 (en, 2012) |
| CS (1) | CS208472B2 (en, 2012) |
| DD (2) | DD140888A5 (en, 2012) |
| DE (2) | DE2857263C3 (en, 2012) |
| DK (1) | DK155740C (en, 2012) |
| EG (1) | EG13869A (en, 2012) |
| FI (1) | FI66003C (en, 2012) |
| FR (2) | FR2393804A1 (en, 2012) |
| GB (1) | GB2000138B (en, 2012) |
| GR (1) | GR72255B (en, 2012) |
| HK (1) | HK13184A (en, 2012) |
| HU (1) | HU180042B (en, 2012) |
| IE (1) | IE47079B1 (en, 2012) |
| IL (2) | IL54867A (en, 2012) |
| IN (1) | IN149747B (en, 2012) |
| IT (1) | IT1096381B (en, 2012) |
| KE (1) | KE3355A (en, 2012) |
| LU (1) | LU79774A1 (en, 2012) |
| MY (1) | MY8500092A (en, 2012) |
| NL (2) | NL180009C (en, 2012) |
| NO (2) | NO151746C (en, 2012) |
| NZ (1) | NZ187476A (en, 2012) |
| OA (1) | OA05964A (en, 2012) |
| PH (3) | PH26810A (en, 2012) |
| PL (1) | PL114501B1 (en, 2012) |
| PT (1) | PT68146A (en, 2012) |
| SE (2) | SE436206B (en, 2012) |
| SG (1) | SG65383G (en, 2012) |
| SU (1) | SU860706A1 (en, 2012) |
| YU (1) | YU41829B (en, 2012) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| LU77306A1 (en, 2012) * | 1977-05-09 | 1979-01-18 | ||
| DE2912511C2 (de) * | 1977-06-07 | 1982-06-24 | Pfizer Inc., 10017 New York, N.Y. | Pharmazeutische Zusammensetzung, enthaltend Penicillansäure |
| DK155942C (da) * | 1977-12-23 | 1989-10-23 | Pfizer | Analogifremgangsmaade til fremstilling af 6-aminopenicillansyre-1,1-dioxid og fysiologisk acceptable syreadditions- og basesalte deraf. |
| JPS54126735A (en) * | 1978-03-24 | 1979-10-02 | Toyama Chem Co Ltd | Bactericidal composition for medical use |
| US4241050A (en) * | 1978-09-01 | 1980-12-23 | Pfizer Inc. | Penam 1,1-dioxides as beta-lactamase inhibitors |
| CA1158639A (en) * | 1978-12-11 | 1983-12-13 | Eric M. Gordon | 6-bromopenicillanic acid sulfone |
| IE49880B1 (en) * | 1979-02-13 | 1986-01-08 | Leo Pharm Prod Ltd | Penicillin derivatives |
| US4714761A (en) * | 1979-03-05 | 1987-12-22 | Pfizer Inc. | 6,6-dihalopenicillanic acid 1,1-dioxides and process |
| US4420426A (en) | 1979-03-05 | 1983-12-13 | Pfizer Inc. | 6-Alpha-halopenicillanic acid 1,1-dioxides |
| SE449103B (sv) * | 1979-03-05 | 1987-04-06 | Pfizer | Sett att framstella penicillansyra-1,1-dioxid samt estrar derav |
| GB2045236A (en) * | 1979-03-26 | 1980-10-29 | Hoechst Uk Ltd | Oxapenem derivatives |
| US4309347A (en) | 1979-05-16 | 1982-01-05 | Pfizer Inc. | Penicillanoyloxymethyl penicillanate 1,1,1',1'-tetraoxide |
| US4377524A (en) | 1979-05-16 | 1983-03-22 | Pfizer Inc. | Bis-esters of methanediol with penicillins and penicillanic acid 1,1-dioxide |
| US4244951A (en) | 1979-05-16 | 1981-01-13 | Pfizer Inc. | Bis-esters of methanediol with penicillins and penicillanic acid 1,1-dioxide |
| IL59948A0 (en) * | 1979-05-21 | 1980-06-30 | Rech Applications Therap | Penicillanic acid derivatives,their production and pharmaceutical compositions containing them |
| DE3051044C2 (en, 2012) * | 1979-06-19 | 1989-03-30 | Leo Pharmaceutical Products Ltd. A/S (Loevens Kemiske Fabrik Produktionsaktieselskab), Ballerup, Dk | |
| US4256733A (en) * | 1979-09-26 | 1981-03-17 | Pfizer Inc. | Acetoxymethyl penam compounds as β-lactamase inhibitors |
| US4432970A (en) * | 1979-11-23 | 1984-02-21 | Pfizer Inc. | 6-beta-Halopenicillanic acid 1,1-dioxides as beta-lactamase inhibitors |
| IL61880A (en) * | 1980-01-21 | 1984-11-30 | Bristol Myers Co | 2beta-chloromethyl-2alpha-methylpenam-3alpha-carboxylic acid sulfone derivatives,their preparation and pharmaceutical compositions containing them |
| US4488994A (en) * | 1980-09-08 | 1984-12-18 | Pfizer Inc. | Bis-esters of methanediol with penicillins and penicillanic acid 1,1-dioxide |
| US4432903A (en) * | 1980-09-08 | 1984-02-21 | Pfizer Inc. | Bis-esters of methanediol with penicillins and penicillanic acid 1,1-dioxide |
| US4474698A (en) * | 1980-12-11 | 1984-10-02 | Pfizer Inc. | Process for preparing esters of penicillanic acid sulfone |
| US4419284A (en) * | 1981-03-23 | 1983-12-06 | Pfizer Inc. | Preparation of halomethyl esters (and related esters) of penicillanic acid 1,1-dioxide |
| DE3261759D1 (en) * | 1981-07-15 | 1985-02-14 | Kanebo Ltd | Novel ester of 1,1-dioxopenicillanic acid, process for production thereof, and use thereof as beta-lactamase inhibitor |
| PT76527B (en) * | 1982-04-19 | 1985-12-09 | Gist Brocades Nv | A process for the preparation of penicillanic acid 1,1-dioxide and derivatives thereof |
| US4502988A (en) * | 1983-08-08 | 1985-03-05 | Eli Lilly And Company | Oxidation process |
| EP0139047A1 (en) * | 1983-10-18 | 1985-05-02 | Gist-Brocades N.V. | Process for the preparation of 6,6-dibromopenicillanic acid 1,1-dioxide |
| US4647457A (en) * | 1983-12-16 | 1987-03-03 | Hoffmann-La Roche Inc. | Penicillanic acid derivatives |
| WO1987006230A1 (en) * | 1986-04-10 | 1987-10-22 | Leo Pharmaceutical Products Ltd. A/S | Method for preparing penicillanic acid derivatives |
| GB8808701D0 (en) * | 1988-04-13 | 1988-05-18 | Erba Carlo Spa | Beta-lactam derivatives |
| CN102977120B (zh) * | 2012-12-14 | 2015-05-27 | 江西富祥药业股份有限公司 | 一种舒巴坦匹酯制备及结晶方法 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3197466A (en) * | 1961-10-30 | 1965-07-27 | Smith Kline French Lab | Penicillin sulfoxides and process |
| LU77306A1 (en, 2012) * | 1977-05-09 | 1979-01-18 | ||
| JPS5439090A (en) * | 1977-07-13 | 1979-03-24 | Glaxo Group Ltd | Betaalactam compound and its preparation |
-
1978
- 1978-05-04 IN IN327/DEL/78A patent/IN149747B/en unknown
- 1978-05-09 PH PH21116A patent/PH26810A/en unknown
- 1978-05-16 YU YU1170/78A patent/YU41829B/xx unknown
- 1978-05-18 OA OA56500A patent/OA05964A/xx unknown
- 1978-05-20 EG EG322/78A patent/EG13869A/xx active
- 1978-05-30 BG BG042176A patent/BG34615A3/xx unknown
- 1978-05-30 BG BG039910A patent/BG34614A3/xx unknown
- 1978-06-01 CS CS783579A patent/CS208472B2/cs unknown
- 1978-06-02 AU AU36838/78A patent/AU513636B2/en not_active Ceased
- 1978-06-02 GB GB7826308A patent/GB2000138B/en not_active Expired
- 1978-06-05 DE DE2857263A patent/DE2857263C3/de not_active Expired
- 1978-06-05 DE DE2824535A patent/DE2824535C3/de not_active Expired
- 1978-06-05 GR GR56439A patent/GR72255B/el unknown
- 1978-06-06 NZ NZ187476A patent/NZ187476A/xx unknown
- 1978-06-06 IT IT24270/78A patent/IT1096381B/it active Protection Beyond IP Right Term
- 1978-06-06 HU HU78PI630A patent/HU180042B/hu unknown
- 1978-06-06 SE SE7806628A patent/SE436206B/sv not_active IP Right Cessation
- 1978-06-06 AT AT411278A patent/AT360649B/de active Protection Beyond IP Right Term
- 1978-06-06 FI FI781800A patent/FI66003C/fi not_active IP Right Cessation
- 1978-06-06 DK DK251478A patent/DK155740C/da not_active IP Right Cessation
- 1978-06-06 SU SU782624408A patent/SU860706A1/ru active
- 1978-06-06 PL PL1978207396A patent/PL114501B1/pl unknown
- 1978-06-06 FR FR787816893A patent/FR2393804A1/fr active Granted
- 1978-06-06 CH CH618078A patent/CH634073A5/fr not_active IP Right Cessation
- 1978-06-06 NL NLAANVRAGE7806126,A patent/NL180009C/xx not_active IP Right Cessation
- 1978-06-06 IL IL54867A patent/IL54867A/xx unknown
- 1978-06-06 NO NO781970A patent/NO151746C/no unknown
- 1978-06-06 BE BE188352A patent/BE867859A/xx not_active IP Right Cessation
- 1978-06-06 LU LU79774A patent/LU79774A1/fr unknown
- 1978-06-06 PT PT68146A patent/PT68146A/pt unknown
- 1978-06-06 IE IE1140/78A patent/IE47079B1/en not_active IP Right Cessation
- 1978-06-07 DD DD78205839A patent/DD140888A5/de unknown
- 1978-06-07 DD DD78218400A patent/DD148585A5/de unknown
- 1978-08-18 AR AR272228A patent/AR224111A1/es active
- 1978-09-08 PH PH21586A patent/PH21116A/en unknown
- 1978-09-08 PH PH21587A patent/PH16465A/en unknown
- 1978-09-19 FR FR787826789A patent/FR2393805A1/fr active Granted
-
1980
- 1980-03-07 AT AT0128580A patent/AT364084B/de not_active IP Right Cessation
-
1981
- 1981-02-19 IL IL62168A patent/IL62168A0/xx unknown
-
1982
- 1982-09-15 NO NO823126A patent/NO152448C/no unknown
-
1983
- 1983-10-27 SE SE8305916A patent/SE447995B/xx not_active IP Right Cessation
- 1983-11-02 SG SG653/83A patent/SG65383G/en unknown
- 1983-11-22 KE KE3355A patent/KE3355A/xx unknown
-
1984
- 1984-02-16 HK HK131/84A patent/HK13184A/xx not_active IP Right Cessation
-
1985
- 1985-12-30 MY MY92/85A patent/MY8500092A/xx unknown
-
1993
- 1993-06-11 NL NL930064C patent/NL930064I2/nl unknown
Also Published As
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |