SE447259B - Forfarande for framstellning av ett 1-n-/l-(-)-omega-amino-alfa-hydroxialkanoyl/kanamycin a eller b - Google Patents
Forfarande for framstellning av ett 1-n-/l-(-)-omega-amino-alfa-hydroxialkanoyl/kanamycin a eller bInfo
- Publication number
- SE447259B SE447259B SE7804973A SE7804973A SE447259B SE 447259 B SE447259 B SE 447259B SE 7804973 A SE7804973 A SE 7804973A SE 7804973 A SE7804973 A SE 7804973A SE 447259 B SE447259 B SE 447259B
- Authority
- SE
- Sweden
- Prior art keywords
- kanamycin
- acid
- mmol
- silyl
- mixture
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 43
- 229960000318 kanamycin Drugs 0.000 claims description 161
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 claims description 134
- 229930182823 kanamycin A Natural products 0.000 claims description 130
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 96
- 238000002360 preparation method Methods 0.000 claims description 53
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 52
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 45
- 239000002253 acid Substances 0.000 claims description 40
- 229960001192 bekanamycin Drugs 0.000 claims description 40
- SKKLOUVUUNMCJE-FQSMHNGLSA-N kanamycin B Chemical compound N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SKKLOUVUUNMCJE-FQSMHNGLSA-N 0.000 claims description 39
- 229930182824 kanamycin B Natural products 0.000 claims description 37
- 230000000903 blocking effect Effects 0.000 claims description 29
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- 239000007858 starting material Substances 0.000 claims description 16
- 150000002148 esters Chemical class 0.000 claims description 13
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims description 11
- 239000003960 organic solvent Substances 0.000 claims description 10
- 125000003277 amino group Chemical group 0.000 claims description 8
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 8
- 231100000252 nontoxic Toxicity 0.000 claims description 8
- 230000003000 nontoxic effect Effects 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- 150000008065 acid anhydrides Chemical class 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 claims description 4
- 239000005711 Benzoic acid Substances 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 235000010233 benzoic acid Nutrition 0.000 claims description 4
- NJAPCAIWQRPQPY-UHFFFAOYSA-N benzyl hydrogen carbonate Chemical compound OC(=O)OCC1=CC=CC=C1 NJAPCAIWQRPQPY-UHFFFAOYSA-N 0.000 claims description 4
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 claims description 4
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 206
- 239000000243 solution Substances 0.000 description 91
- 239000000203 mixture Substances 0.000 description 88
- 229960004821 amikacin Drugs 0.000 description 82
- LKCWBDHBTVXHDL-RMDFUYIESA-N amikacin Chemical compound O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O1)O)NC(=O)[C@@H](O)CCN)[C@H]1O[C@H](CN)[C@@H](O)[C@H](O)[C@H]1O LKCWBDHBTVXHDL-RMDFUYIESA-N 0.000 description 77
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 76
- 238000005917 acylation reaction Methods 0.000 description 66
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 65
- 230000010933 acylation Effects 0.000 description 62
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 47
- 239000000047 product Substances 0.000 description 42
- 238000003756 stirring Methods 0.000 description 42
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
- 239000000463 material Substances 0.000 description 40
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 36
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 32
- 239000003054 catalyst Substances 0.000 description 32
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 29
- 239000000706 filtrate Substances 0.000 description 25
- 239000007787 solid Substances 0.000 description 25
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 238000005406 washing Methods 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- -1 diglym Chemical compound 0.000 description 22
- 229930027917 kanamycin Natural products 0.000 description 22
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 21
- 150000001875 compounds Chemical class 0.000 description 21
- 238000006884 silylation reaction Methods 0.000 description 21
- 239000002904 solvent Substances 0.000 description 20
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 20
- SWOHHBNJQHDNFM-WYSMZKEGSA-N (2s)-4-amino-n-[(1s,2r,3r,4s,5r)-5-amino-4-[(2s,3r,4s,5s,6r)-4-amino-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2-[(2r,3r,4s,5s,6r)-6-(aminomethyl)-3,4,5-trihydroxyoxan-2-yl]oxy-3-hydroxycyclohexyl]-2-hydroxybutanamide;sulfuric acid Chemical compound OS(O)(=O)=O.OS(O)(=O)=O.O([C@H]1[C@H](N)C[C@@H]([C@H]([C@@H]1O)O[C@@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CN)O1)O)NC(=O)[C@@H](O)CCN)[C@H]1O[C@H](CO)[C@@H](O)[C@H](N)[C@H]1O SWOHHBNJQHDNFM-WYSMZKEGSA-N 0.000 description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- 238000006243 chemical reaction Methods 0.000 description 18
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 17
- 239000007864 aqueous solution Substances 0.000 description 16
- 239000001257 hydrogen Substances 0.000 description 16
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 15
- 235000011114 ammonium hydroxide Nutrition 0.000 description 15
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 15
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 14
- 238000004458 analytical method Methods 0.000 description 14
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 14
- 238000010828 elution Methods 0.000 description 14
- 239000007788 liquid Substances 0.000 description 13
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical compound CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 description 12
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
- 239000002808 molecular sieve Substances 0.000 description 12
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 12
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 12
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 11
- 235000019439 ethyl acetate Nutrition 0.000 description 11
- 229910052757 nitrogen Inorganic materials 0.000 description 11
- 239000011541 reaction mixture Substances 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- 239000000908 ammonium hydroxide Substances 0.000 description 10
- 238000012543 microbiological analysis Methods 0.000 description 10
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 9
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- 150000008064 anhydrides Chemical class 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- ZUSSTQCWRDLYJA-UHFFFAOYSA-N n-hydroxy-5-norbornene-2,3-dicarboximide Chemical compound C1=CC2CC1C1C2C(=O)N(O)C1=O ZUSSTQCWRDLYJA-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
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- 239000012299 nitrogen atmosphere Substances 0.000 description 7
- 239000002002 slurry Substances 0.000 description 7
- QPEJHSFTZVMSJH-UHFFFAOYSA-N 3-amino-5-hydroxybenzoic acid Chemical compound NC1=CC(O)=CC(C(O)=O)=C1 QPEJHSFTZVMSJH-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
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- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 229910052763 palladium Inorganic materials 0.000 description 6
- KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 description 5
- 241000588724 Escherichia coli Species 0.000 description 5
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- 238000004809 thin layer chromatography Methods 0.000 description 5
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 4
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
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- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
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- 230000002906 microbiologic effect Effects 0.000 description 1
- LULXBAGMGMJJRW-UHFFFAOYSA-N n,2-bis(trimethylsilyl)acetamide Chemical compound C[Si](C)(C)CC(=O)N[Si](C)(C)C LULXBAGMGMJJRW-UHFFFAOYSA-N 0.000 description 1
- JDAZWPXJRMBEQL-UHFFFAOYSA-N n,n'-di(propan-2-yl)methanediimine;methanediimine Chemical compound N=C=N.CC(C)N=C=NC(C)C JDAZWPXJRMBEQL-UHFFFAOYSA-N 0.000 description 1
- 229940078487 nickel acetate tetrahydrate Drugs 0.000 description 1
- OINIXPNQKAZCRL-UHFFFAOYSA-L nickel(2+);diacetate;tetrahydrate Chemical compound O.O.O.O.[Ni+2].CC([O-])=O.CC([O-])=O OINIXPNQKAZCRL-UHFFFAOYSA-L 0.000 description 1
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
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- 235000017281 sodium acetate Nutrition 0.000 description 1
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- 235000011152 sodium sulphate Nutrition 0.000 description 1
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- 125000001424 substituent group Chemical group 0.000 description 1
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- 239000011593 sulfur Substances 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
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- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- AATYKEFFPLPLST-UHFFFAOYSA-N trimethylsilylurea Chemical compound C[Si](C)(C)NC(N)=O AATYKEFFPLPLST-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/22—Cyclohexane rings, substituted by nitrogen atoms
- C07H15/222—Cyclohexane rings substituted by at least two nitrogen atoms
- C07H15/226—Cyclohexane rings substituted by at least two nitrogen atoms with at least two saccharide radicals directly attached to the cyclohexane rings
- C07H15/234—Cyclohexane rings substituted by at least two nitrogen atoms with at least two saccharide radicals directly attached to the cyclohexane rings attached to non-adjacent ring carbon atoms of the cyclohexane rings, e.g. kanamycins, tobramycin, nebramycin, gentamicin A2
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Saccharide Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US79180677A | 1977-04-28 | 1977-04-28 | |
| US88858578A | 1978-03-20 | 1978-03-20 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SE7804973L SE7804973L (sv) | 1978-10-29 |
| SE447259B true SE447259B (sv) | 1986-11-03 |
Family
ID=27121201
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SE7804973A SE447259B (sv) | 1977-04-28 | 1978-04-28 | Forfarande for framstellning av ett 1-n-/l-(-)-omega-amino-alfa-hydroxialkanoyl/kanamycin a eller b |
| SE8305538A SE461148B (sv) | 1977-04-28 | 1983-10-07 | Polysilylerat kanamycin a eller b derivat |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SE8305538A SE461148B (sv) | 1977-04-28 | 1983-10-07 | Polysilylerat kanamycin a eller b derivat |
Country Status (27)
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS55306A (en) * | 1978-04-28 | 1980-01-05 | Bristol Myers Co | Manufacture of 11nn*omegaaaminooalphaahydroxy alkanoyl**aminoglycoside antibiotic |
| JP4621429B2 (ja) * | 2002-02-19 | 2011-01-26 | 学校法人東海大学 | 乳酸誘導体 |
| AU2008326297B2 (en) | 2007-11-21 | 2012-11-08 | Cipla USA, Inc. | Antibacterial aminoglycoside analogs |
| WO2010132759A1 (en) | 2009-05-15 | 2010-11-18 | Achaogen, Inc. | Antibacterial derivatives of dibekacin |
| WO2010132760A1 (en) | 2009-05-15 | 2010-11-18 | Achaogen, Inc. | Antibacterial derivatives of tobramycin |
| WO2010132765A2 (en) | 2009-05-15 | 2010-11-18 | Achaogen, Inc. | Antibacterial aminoglycoside analogs |
| WO2010132757A2 (en) * | 2009-05-15 | 2010-11-18 | Achaogen, Inc. | Antibacterial aminoglycoside analogs |
| WO2010132768A1 (en) | 2009-05-15 | 2010-11-18 | Achaogen, Inc. | Antibacterial derivatives of sisomicin |
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1978
- 1978-04-21 AR AR271852A patent/AR218910A1/es active
- 1978-04-25 CA CA301,968A patent/CA1105454A/en not_active Expired
- 1978-04-25 FI FI781288A patent/FI781288A7/fi not_active Application Discontinuation
- 1978-04-25 NO NO781437A patent/NO149635C/no unknown
- 1978-04-25 CA CA301,962A patent/CA1100953A/en not_active Expired
- 1978-04-26 DK DK182978A patent/DK165450C/da not_active IP Right Cessation
- 1978-04-26 DK DK197801830A patent/DK172543B1/da not_active IP Right Cessation
- 1978-04-26 CY CY1241A patent/CY1241A/en unknown
- 1978-04-26 NL NLAANVRAGE7804503,A patent/NL178790C/xx not_active IP Right Cessation
- 1978-04-26 GB GB16571/78A patent/GB1598294A/en not_active Expired
- 1978-04-27 PT PT67959A patent/PT67959B/pt unknown
- 1978-04-27 LU LU79541A patent/LU79541A1/xx unknown
- 1978-04-27 YU YU1024/78A patent/YU41590B/xx unknown
- 1978-04-27 FR FR7812589A patent/FR2388826A1/fr active Granted
- 1978-04-27 YU YU01025/78A patent/YU102578A/xx unknown
- 1978-04-27 CS CS782729A patent/CS207607B2/cs unknown
- 1978-04-27 IE IE841/78A patent/IE46945B1/en not_active IP Right Cessation
- 1978-04-27 FR FR7812591A patent/FR2388827A1/fr active Granted
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- 1978-04-28 JP JP5016078A patent/JPS53149951A/ja active Granted
- 1978-04-28 DE DE19782818822 patent/DE2818822A1/de active Granted
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- 1978-04-28 ES ES469303A patent/ES469303A1/es not_active Expired
- 1978-04-28 DE DE19782818992 patent/DE2818992A1/de active Granted
- 1978-04-28 IT IT49137/78A patent/IT1105500B/it active
- 1978-04-28 IT IT49136/78A patent/IT1156718B/it active
- 1978-04-28 AT AT312778A patent/AT357675B/de not_active IP Right Cessation
- 1978-04-28 CH CH470278A patent/CH639104A5/de not_active IP Right Cessation
- 1978-04-28 PL PL1978206457A patent/PL117307B1/pl unknown
- 1978-04-29 EG EG283/78A patent/EG13710A/xx active
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1983
- 1983-04-05 NO NO83831197A patent/NO154697C/no unknown
- 1983-10-07 SE SE8305538A patent/SE461148B/sv not_active IP Right Cessation
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1984
- 1984-03-12 SG SG228/84A patent/SG22884G/en unknown
- 1984-04-12 KE KE3398A patent/KE3398A/xx unknown
- 1984-06-22 HK HK514/84A patent/HK51484A/en not_active IP Right Cessation
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1985
- 1985-12-30 MY MY528/85A patent/MY8500528A/xx unknown
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