DD294265A5 - Substituierte aminoalkylphosphinsaeuren und verfahren zu deren herstellung - Google Patents
Substituierte aminoalkylphosphinsaeuren und verfahren zu deren herstellung Download PDFInfo
- Publication number
- DD294265A5 DD294265A5 DD90340576A DD34057690A DD294265A5 DD 294265 A5 DD294265 A5 DD 294265A5 DD 90340576 A DD90340576 A DD 90340576A DD 34057690 A DD34057690 A DD 34057690A DD 294265 A5 DD294265 A5 DD 294265A5
- Authority
- DD
- German Democratic Republic
- Prior art keywords
- acid
- hydrogen
- amino
- formula
- salt
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 64
- 239000001257 hydrogen Substances 0.000 claims abstract description 74
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 74
- 150000003839 salts Chemical class 0.000 claims abstract description 72
- 239000002253 acid Substances 0.000 claims abstract description 45
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 42
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 36
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 30
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 26
- 150000002367 halogens Chemical class 0.000 claims abstract description 26
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 22
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 21
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 18
- 150000007513 acids Chemical class 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims description 131
- 239000000203 mixture Substances 0.000 claims description 49
- 230000002829 reductive effect Effects 0.000 claims description 43
- -1 alkali metal salts Chemical class 0.000 claims description 40
- 239000002585 base Substances 0.000 claims description 28
- 239000007858 starting material Substances 0.000 claims description 23
- 230000008569 process Effects 0.000 claims description 22
- CJTIGOOCRLKWAP-UHFFFAOYSA-N (3-amino-2-oxopropyl)-methylphosphinic acid Chemical compound CP(O)(=O)CC(=O)CN CJTIGOOCRLKWAP-UHFFFAOYSA-N 0.000 claims description 20
- 229910052783 alkali metal Inorganic materials 0.000 claims description 18
- NHVRIDDXGZPJTJ-UHFFFAOYSA-N skf-97,541 Chemical compound CP(O)(=O)CCCN NHVRIDDXGZPJTJ-UHFFFAOYSA-N 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 15
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
- 150000003863 ammonium salts Chemical class 0.000 claims description 12
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 11
- FUUPFUIGNBPCAY-UHFFFAOYSA-N (3-amino-2-hydroxypropyl)-methylphosphinic acid Chemical compound CP(O)(=O)CC(O)CN FUUPFUIGNBPCAY-UHFFFAOYSA-N 0.000 claims description 10
- 150000001340 alkali metals Chemical class 0.000 claims description 10
- 150000001721 carbon Chemical group 0.000 claims description 10
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 10
- 125000003277 amino group Chemical group 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 7
- 239000000543 intermediate Substances 0.000 claims description 7
- 229940124531 pharmaceutical excipient Drugs 0.000 claims description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 125000006239 protecting group Chemical group 0.000 claims description 4
- VHBRTSZUHRQZQW-UHFFFAOYSA-N (3-amino-1-hydroxypropyl)-methylphosphinic acid Chemical compound CP(O)(=O)C(O)CCN VHBRTSZUHRQZQW-UHFFFAOYSA-N 0.000 claims description 3
- CCGFQGUALPHBIC-UHFFFAOYSA-N 1-aminopentan-3-yl(methyl)phosphinic acid Chemical compound CCC(P(C)(O)=O)CCN CCGFQGUALPHBIC-UHFFFAOYSA-N 0.000 claims description 3
- TXAHGWWWANKBDA-UHFFFAOYSA-N 3-aminopropyl(difluoromethyl)phosphinic acid Chemical compound NCCCP(O)(=O)C(F)F TXAHGWWWANKBDA-UHFFFAOYSA-N 0.000 claims description 3
- HYJASQZKKPPJKA-UHFFFAOYSA-N 3-aminopropyl(fluoromethyl)phosphinic acid Chemical compound NCCCP(O)(=O)CF HYJASQZKKPPJKA-UHFFFAOYSA-N 0.000 claims description 3
- DRVJVRJSFKFGIS-UHFFFAOYSA-N 3-aminopropyl(trifluoromethyl)phosphinic acid Chemical compound NCCCP(O)(=O)C(F)(F)F DRVJVRJSFKFGIS-UHFFFAOYSA-N 0.000 claims description 3
- CCFBFTKQKRGULP-UHFFFAOYSA-N 4-aminobutan-2-yl(methyl)phosphinic acid Chemical compound CP(=O)(O)C(C)CCN CCFBFTKQKRGULP-UHFFFAOYSA-N 0.000 claims description 3
- FUUPFUIGNBPCAY-SCSAIBSYSA-N [(2r)-3-amino-2-hydroxypropyl]-methylphosphinic acid Chemical compound CP(O)(=O)C[C@H](O)CN FUUPFUIGNBPCAY-SCSAIBSYSA-N 0.000 claims description 3
- FUUPFUIGNBPCAY-BYPYZUCNSA-N [(2s)-3-amino-2-hydroxypropyl]-methylphosphinic acid Chemical compound CP(O)(=O)C[C@@H](O)CN FUUPFUIGNBPCAY-BYPYZUCNSA-N 0.000 claims description 3
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 claims description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 18
- XYRPBUKHKWHPDI-UHFFFAOYSA-N (4-amino-1,1,1-trifluorobutan-2-yl)-methylphosphinic acid Chemical compound CP(O)(=O)C(C(F)(F)F)CCN XYRPBUKHKWHPDI-UHFFFAOYSA-N 0.000 claims 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims 2
- 239000007795 chemical reaction product Substances 0.000 claims 1
- 239000012059 conventional drug carrier Substances 0.000 claims 1
- BCDIWLCKOCHCIH-UHFFFAOYSA-N methylphosphinic acid Chemical compound CP(O)=O BCDIWLCKOCHCIH-UHFFFAOYSA-N 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 25
- 208000008238 Muscle Spasticity Diseases 0.000 abstract description 2
- 208000002193 Pain Diseases 0.000 abstract description 2
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 abstract description 2
- 206010008129 cerebral palsy Diseases 0.000 abstract description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 2
- 201000006417 multiple sclerosis Diseases 0.000 abstract description 2
- 208000018198 spasticity Diseases 0.000 abstract description 2
- 206010013754 Drug withdrawal syndrome Diseases 0.000 abstract 1
- 239000000556 agonist Substances 0.000 abstract 1
- 208000004296 neuralgia Diseases 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 109
- 239000000243 solution Substances 0.000 description 47
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
- 238000006243 chemical reaction Methods 0.000 description 31
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 24
- 239000002904 solvent Substances 0.000 description 21
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
- 239000003921 oil Substances 0.000 description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 239000004480 active ingredient Substances 0.000 description 15
- 239000012298 atmosphere Substances 0.000 description 14
- 239000012043 crude product Substances 0.000 description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 12
- 239000011261 inert gas Substances 0.000 description 12
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 11
- 239000003054 catalyst Substances 0.000 description 11
- 239000003480 eluent Substances 0.000 description 11
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 11
- 238000002844 melting Methods 0.000 description 11
- 230000008018 melting Effects 0.000 description 11
- 238000001394 phosphorus-31 nuclear magnetic resonance spectrum Methods 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 10
- 235000019341 magnesium sulphate Nutrition 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 238000009835 boiling Methods 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- 239000003826 tablet Substances 0.000 description 9
- KPYSYYIEGFHWSV-UHFFFAOYSA-N Baclofen Chemical compound OC(=O)CC(CN)C1=CC=C(Cl)C=C1 KPYSYYIEGFHWSV-UHFFFAOYSA-N 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- 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 8
- 239000010410 layer Substances 0.000 description 8
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 229960000794 baclofen Drugs 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 239000013058 crude material Substances 0.000 description 7
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- 239000002244 precipitate Substances 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 235000019359 magnesium stearate Nutrition 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 6
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 5
- 239000007868 Raney catalyst Substances 0.000 description 5
- 229910000564 Raney nickel Inorganic materials 0.000 description 5
- 229910021529 ammonia Inorganic materials 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 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 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 4
- 229960001701 chloroform Drugs 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 238000005984 hydrogenation reaction Methods 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
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- 239000012230 colorless oil Substances 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
- 238000007327 hydrogenolysis reaction Methods 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
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- 239000011592 zinc chloride Substances 0.000 description 3
- 235000005074 zinc chloride Nutrition 0.000 description 3
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- MFJYEFLIZKJOLC-ARAKYBCZSA-N (2r)-1-azido-3-[methyl(2-methylpropoxy)phosphoryl]propan-2-ol Chemical compound CC(C)COP(C)(=O)C[C@H](O)CN=[N+]=[N-] MFJYEFLIZKJOLC-ARAKYBCZSA-N 0.000 description 2
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- YHUJUEBUZZPNDY-UHFFFAOYSA-N 2-[3-[methyl(2-methylpropoxy)phosphoryl]prop-2-enyl]isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CC=CP(C)(=O)OCC(C)C)C(=O)C2=C1 YHUJUEBUZZPNDY-UHFFFAOYSA-N 0.000 description 2
- VSMWYMMFPCPLOR-UHFFFAOYSA-N 3-[diethoxymethyl(ethoxy)phosphoryl]pentan-1-amine Chemical compound CCOC(OCC)P(=O)(OCC)C(CC)CCN VSMWYMMFPCPLOR-UHFFFAOYSA-N 0.000 description 2
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- UXSGNBGTYFOGDS-UHFFFAOYSA-N 3-[difluoromethyl(ethoxy)phosphoryl]propan-1-amine Chemical compound CCOP(=O)(C(F)F)CCCN UXSGNBGTYFOGDS-UHFFFAOYSA-N 0.000 description 2
- BURLSGPZAQXCMZ-UHFFFAOYSA-N 3-[difluoromethyl(ethoxy)phosphoryl]propanenitrile Chemical compound CCOP(=O)(C(F)F)CCC#N BURLSGPZAQXCMZ-UHFFFAOYSA-N 0.000 description 2
- PQLMYOIJBKXXTA-UHFFFAOYSA-N 3-[ethoxy(methyl)phosphoryl]-4,4,4-trifluorobutan-1-amine;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOP(C)(=O)C(C(F)(F)F)CCN PQLMYOIJBKXXTA-UHFFFAOYSA-N 0.000 description 2
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- KBQUKFHDWHGAOH-UHFFFAOYSA-N 3-[methyl(2-methylpropoxy)phosphoryl]propan-1-amine Chemical compound CC(C)COP(C)(=O)CCCN KBQUKFHDWHGAOH-UHFFFAOYSA-N 0.000 description 2
- FZCMREWADROMJN-UHFFFAOYSA-N 3-aminoprop-1-enyl(methyl)phosphinic acid Chemical compound CP(O)(=O)C=CCN FZCMREWADROMJN-UHFFFAOYSA-N 0.000 description 2
- 239000003185 4 aminobutyric acid B receptor stimulating agent Substances 0.000 description 2
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- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
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- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
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- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
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- 150000004678 hydrides Chemical class 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000004692 metal hydroxides Chemical class 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- XARAJPHSZHJORY-UHFFFAOYSA-N methoxy(2-methylpropoxy)phosphane Chemical compound COPOCC(C)C XARAJPHSZHJORY-UHFFFAOYSA-N 0.000 description 1
- UIWOZHBYBSGCOS-UHFFFAOYSA-N methoxy(oxido)phosphanium Chemical compound CO[PH2]=O UIWOZHBYBSGCOS-UHFFFAOYSA-N 0.000 description 1
- RMSQWTQLAUEIDC-UHFFFAOYSA-N methyl 2-[2-[(2-methylpropan-2-yl)oxycarbonyl]hydrazinyl]acetate Chemical compound COC(=O)CNNC(=O)OC(C)(C)C RMSQWTQLAUEIDC-UHFFFAOYSA-N 0.000 description 1
- YIZNYMADIRZRAL-UHFFFAOYSA-N methyl(propan-2-yloxy)phosphinous acid Chemical compound CC(C)OP(C)O YIZNYMADIRZRAL-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229940035363 muscle relaxants Drugs 0.000 description 1
- 239000003158 myorelaxant agent Substances 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000006606 n-butoxy group Chemical group 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- OEELFULYSIVRQT-UHFFFAOYSA-N o-ethyl n-(1h-imidazol-2-yl)carbamothioate Chemical class CCOC(=S)NC1=NC=CN1 OEELFULYSIVRQT-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 150000001451 organic peroxides Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 150000002924 oxiranes Chemical class 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 125000005544 phthalimido group Chemical group 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- SCPYDCQAZCOKTP-UHFFFAOYSA-N silanol Chemical compound [SiH3]O SCPYDCQAZCOKTP-UHFFFAOYSA-N 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- RZWQDAUIUBVCDD-UHFFFAOYSA-M sodium;benzenethiolate Chemical compound [Na+].[S-]C1=CC=CC=C1 RZWQDAUIUBVCDD-UHFFFAOYSA-M 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000001300 stimulation of adenylate cyclase Effects 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 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
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001382 thioacetal group Chemical group 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- VPAYJEUHKVESSD-UHFFFAOYSA-N trifluoroiodomethane Chemical compound FC(F)(F)I VPAYJEUHKVESSD-UHFFFAOYSA-N 0.000 description 1
- 206010044652 trigeminal neuralgia Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/36—Amides thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/301—Acyclic saturated acids which can have further substituents on alkyl
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Neurology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Treatments For Attaching Organic Compounds To Fibrous Goods (AREA)
- Luminescent Compositions (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Detergent Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB898911017A GB8911017D0 (en) | 1989-05-13 | 1989-05-13 | Substituted aminoalkylphosphinic acids |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DD294265A5 true DD294265A5 (de) | 1991-09-26 |
Family
ID=10656689
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DD90340576A DD294265A5 (de) | 1989-05-13 | 1990-05-11 | Substituierte aminoalkylphosphinsaeuren und verfahren zu deren herstellung |
Country Status (24)
| Country | Link |
|---|---|
| EP (1) | EP0399949B1 (sh) |
| JP (1) | JP2930366B2 (sh) |
| KR (1) | KR0159501B1 (sh) |
| AT (1) | ATE121095T1 (sh) |
| AU (1) | AU629335B2 (sh) |
| CA (1) | CA2016631C (sh) |
| DD (1) | DD294265A5 (sh) |
| DE (1) | DE69018514T2 (sh) |
| DK (1) | DK0399949T3 (sh) |
| ES (1) | ES2070303T3 (sh) |
| FI (1) | FI94416C (sh) |
| GB (1) | GB8911017D0 (sh) |
| GR (1) | GR3015770T3 (sh) |
| HR (1) | HRP940178A2 (sh) |
| HU (1) | HU206885B (sh) |
| IE (1) | IE66165B1 (sh) |
| IL (1) | IL94317A (sh) |
| MX (1) | MX20639A (sh) |
| NO (1) | NO176761C (sh) |
| NZ (1) | NZ233647A (sh) |
| PT (1) | PT94014B (sh) |
| SI (1) | SI9010917B (sh) |
| YU (1) | YU91790A (sh) |
| ZA (1) | ZA903611B (sh) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0767174A1 (de) * | 1991-11-21 | 1997-04-09 | Ciba-Geigy Ag | Neue Aminoalkanphosphinsäuren und ihre Salze |
| BR9710536A (pt) | 1996-07-24 | 1999-08-17 | Warner Lambert Co | Isobutilgaba e seus derivados para o tratamento da dor |
| EE200100027A (et) | 1998-07-15 | 2002-06-17 | Jomaa Hassan | Fosfororgaanilised ühendid, neid sisaldav farmatseutiline preparaat ja nende kasutamine |
| GB9906882D0 (en) * | 1999-03-25 | 1999-05-19 | Novartis Ag | Organic compounds |
| US7319095B2 (en) | 1999-12-09 | 2008-01-15 | Astrazeneca Ab | Use of GABAB receptor agonists |
| SE9904508D0 (sv) | 1999-12-09 | 1999-12-09 | Astra Ab | New compounds |
| SE9904507D0 (sv) * | 1999-12-09 | 1999-12-09 | Astra Ab | New compounds |
| AR033779A1 (es) | 2001-06-08 | 2004-01-07 | Astrazeneca Ab | Compuestos utiles en la enfermedad de reflujo |
| SE0102055D0 (sv) * | 2001-06-08 | 2001-06-08 | Astrazeneca Ab | New Compounds |
| CA2548917C (en) | 2003-12-11 | 2014-09-23 | Sepracor Inc. | Combination of a sedative and a neurotransmitter modulator, and methods for improving sleep quality and treating depression |
| SE0401653D0 (sv) | 2004-06-24 | 2004-06-24 | Astrazeneca Ab | New compounds |
| CA2632016A1 (en) | 2005-12-23 | 2007-06-28 | Astrazeneca Ab | Imidazole derivatives for the treatment of gastrointestinal disorders |
| EP1968947A1 (en) | 2005-12-23 | 2008-09-17 | AstraZeneca AB | Gaba-b receptor modulators |
| DE102008056228A1 (de) * | 2008-11-06 | 2010-05-12 | Clariant International Limited | Verfahren zur Herstellung von monoaminofunktionalisierten Dialkylphosphinsäuren, deren Salze und Ester und ihre Verwendung |
| DE102008056339A1 (de) * | 2008-11-07 | 2010-05-12 | Clariant International Limited | Verfahren zur Herstellung von mono-aminofunktionalisierten Dialkylphosphinsäuren, -estern und -salzen und ihre Verwendung |
| WO2011113904A1 (en) | 2010-03-17 | 2011-09-22 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Medicaments for the prevention and treatment of a disease associated with retinal ganglion cell degeneration |
| EP2621282B1 (en) | 2010-09-28 | 2020-04-15 | The Regents of The University of California | Gaba agonists in the treatment of disorders associated with metabolic syndrome and gaba combinations in treatment or prophylaxis of type i diabetes |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3311475C1 (de) * | 1983-03-29 | 1984-08-16 | Siemens AG, 1000 Berlin und 8000 München | Mikroprogramm-Steuereinrichtung |
| DE3312165A1 (de) * | 1983-04-02 | 1984-10-04 | Hoechst Ag, 6230 Frankfurt | Verfahren zur herstellung von phosphinothricin |
| GB8728483D0 (en) * | 1987-12-04 | 1988-01-13 | Ciba Geigy Ag | Chemical compounds |
| GB8820266D0 (en) * | 1988-08-26 | 1988-09-28 | Smith Kline French Lab | Compounds |
-
1989
- 1989-05-13 GB GB898911017A patent/GB8911017D0/en active Pending
-
1990
- 1990-05-07 IL IL94317A patent/IL94317A/xx not_active IP Right Cessation
- 1990-05-07 AU AU54809/90A patent/AU629335B2/en not_active Ceased
- 1990-05-08 DK DK90810346.8T patent/DK0399949T3/da active
- 1990-05-08 AT AT90810346T patent/ATE121095T1/de not_active IP Right Cessation
- 1990-05-08 DE DE69018514T patent/DE69018514T2/de not_active Expired - Fee Related
- 1990-05-08 EP EP90810346A patent/EP0399949B1/en not_active Expired - Lifetime
- 1990-05-08 ES ES90810346T patent/ES2070303T3/es not_active Expired - Lifetime
- 1990-05-09 MX MX2063990A patent/MX20639A/es unknown
- 1990-05-10 YU YU91790A patent/YU91790A/sh unknown
- 1990-05-10 SI SI9010917A patent/SI9010917B/sl unknown
- 1990-05-11 ZA ZA903611A patent/ZA903611B/xx unknown
- 1990-05-11 HU HU903012A patent/HU206885B/hu not_active IP Right Cessation
- 1990-05-11 NZ NZ233647A patent/NZ233647A/en unknown
- 1990-05-11 KR KR1019900006687A patent/KR0159501B1/ko not_active IP Right Cessation
- 1990-05-11 PT PT94014A patent/PT94014B/pt not_active IP Right Cessation
- 1990-05-11 NO NO902109A patent/NO176761C/no not_active IP Right Cessation
- 1990-05-11 CA CA002016631A patent/CA2016631C/en not_active Expired - Lifetime
- 1990-05-11 DD DD90340576A patent/DD294265A5/de not_active IP Right Cessation
- 1990-05-11 IE IE171690A patent/IE66165B1/en not_active IP Right Cessation
- 1990-05-11 FI FI902368A patent/FI94416C/fi not_active IP Right Cessation
- 1990-05-14 JP JP2121395A patent/JP2930366B2/ja not_active Expired - Fee Related
-
1994
- 1994-03-18 HR HRP-917/90A patent/HRP940178A2/hr not_active Application Discontinuation
-
1995
- 1995-04-13 GR GR950400747T patent/GR3015770T3/el unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| ENJ | Ceased due to non-payment of renewal fee |