CS216933B2 - Method of making the heterocyclic phenoxyemines - Google Patents
Method of making the heterocyclic phenoxyemines Download PDFInfo
- Publication number
- CS216933B2 CS216933B2 CS804693A CS469380A CS216933B2 CS 216933 B2 CS216933 B2 CS 216933B2 CS 804693 A CS804693 A CS 804693A CS 469380 A CS469380 A CS 469380A CS 216933 B2 CS216933 B2 CS 216933B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- pyrrolidine
- methoxy
- compounds
- mol
- dried
- Prior art date
Links
- 125000000623 heterocyclic group Chemical group 0.000 title 1
- 238000004519 manufacturing process Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 41
- -1 heterocyclic phenoxyamines Chemical class 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 150000001204 N-oxides Chemical class 0.000 claims description 5
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 5
- 239000007858 starting material Substances 0.000 claims description 5
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 125000000129 anionic group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 239000003513 alkali Substances 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-M phenolate Chemical compound [O-]C1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-M 0.000 claims 1
- 229940031826 phenolate Drugs 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 106
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 78
- 239000000243 solution Substances 0.000 description 51
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 45
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 44
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
- 239000002585 base Substances 0.000 description 34
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 33
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 31
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
- 235000019441 ethanol Nutrition 0.000 description 31
- 239000000047 product Substances 0.000 description 31
- 239000000203 mixture Substances 0.000 description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 26
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- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Natural products OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 18
- 238000010992 reflux Methods 0.000 description 16
- 229910021529 ammonia Inorganic materials 0.000 description 15
- 239000007864 aqueous solution Substances 0.000 description 14
- 206010002091 Anaesthesia Diseases 0.000 description 13
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 13
- 230000037005 anaesthesia Effects 0.000 description 13
- 238000001816 cooling Methods 0.000 description 13
- 229910000027 potassium carbonate Inorganic materials 0.000 description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Substances OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 10
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
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- 238000004458 analytical method Methods 0.000 description 9
- 208000003251 Pruritus Diseases 0.000 description 8
- KJFMBFZCATUALV-UHFFFAOYSA-N phenolphthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2C(=O)O1 KJFMBFZCATUALV-UHFFFAOYSA-N 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 238000004809 thin layer chromatography Methods 0.000 description 8
- 230000003444 anaesthetic effect Effects 0.000 description 7
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical class C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 7
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- 239000001530 fumaric acid Substances 0.000 description 7
- 230000007803 itching Effects 0.000 description 7
- 229940095064 tartrate Drugs 0.000 description 7
- 241000700198 Cavia Species 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 238000004090 dissolution Methods 0.000 description 6
- 230000007794 irritation Effects 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- OCQAXYHNMWVLRH-UHFFFAOYSA-N 2,3-dibenzoyl-2,3-dihydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(O)(C(O)=O)C(O)(C(=O)O)C(=O)C1=CC=CC=C1 OCQAXYHNMWVLRH-UHFFFAOYSA-N 0.000 description 5
- RTLULEZPCUMDKR-UHFFFAOYSA-N 2-[2-(3,5-dichloro-2-methoxyphenoxy)ethyl]-1-methylpyrrolidine Chemical compound COC1=C(Cl)C=C(Cl)C=C1OCCC1N(C)CCC1 RTLULEZPCUMDKR-UHFFFAOYSA-N 0.000 description 5
- YFKQRZRAQLZDAZ-UHFFFAOYSA-N 3,5-dichloro-2-methoxyphenol Chemical compound COC1=C(O)C=C(Cl)C=C1Cl YFKQRZRAQLZDAZ-UHFFFAOYSA-N 0.000 description 5
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 239000006210 lotion Substances 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical group CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 5
- 229960004919 procaine Drugs 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- DBARMDUSHJFUOJ-UHFFFAOYSA-N 2-[2-(3,5-dichloro-2-methoxyphenoxy)ethyl]-1-ethylpyrrolidine Chemical compound CCN1CCCC1CCOC1=CC(Cl)=CC(Cl)=C1OC DBARMDUSHJFUOJ-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
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- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- FKCMADOPPWWGNZ-YUMQZZPRSA-N [(2r)-1-[(2s)-2-amino-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1B(O)O FKCMADOPPWWGNZ-YUMQZZPRSA-N 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
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- 238000004821 distillation Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 230000011514 reflex Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- MZVIBFVRXORUIA-UHFFFAOYSA-N 2-[1-(cyclopropylmethyl)pyrrolidin-2-yl]ethanol Chemical compound OCCC1CCCN1CC1CC1 MZVIBFVRXORUIA-UHFFFAOYSA-N 0.000 description 3
- MWFCGPKABKLWSH-UHFFFAOYSA-N 2-[2-(3,5-dichloro-2-methoxyphenoxy)ethyl]-1-ethylpyrrolidine;hydrochloride Chemical compound Cl.CCN1CCCC1CCOC1=CC(Cl)=CC(Cl)=C1OC MWFCGPKABKLWSH-UHFFFAOYSA-N 0.000 description 3
- VBKJZTGQDQHOCK-UHFFFAOYSA-N 3,5-dichloro-2-ethoxyphenol Chemical compound CCOC1=C(O)C=C(Cl)C=C1Cl VBKJZTGQDQHOCK-UHFFFAOYSA-N 0.000 description 3
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
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- 239000002253 acid Substances 0.000 description 3
- 238000010533 azeotropic distillation Methods 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
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- 150000002989 phenols Chemical class 0.000 description 3
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- HWMNZNJLDKPDHA-WLHGVMLRSA-N (e)-but-2-enedioic acid;1-(cyclopropylmethyl)-2-[2-(3,5-dichloro-2-methoxyphenoxy)ethyl]pyrrolidine Chemical compound OC(=O)\C=C\C(O)=O.COC1=C(Cl)C=C(Cl)C=C1OCCC1N(CC2CC2)CCC1 HWMNZNJLDKPDHA-WLHGVMLRSA-N 0.000 description 2
- NRSCVKWUVWTXAD-WLHGVMLRSA-N (e)-but-2-enedioic acid;2-[2-(3,5-dibromo-2-methoxyphenoxy)ethyl]-1-methylpyrrolidine Chemical compound OC(=O)\C=C\C(O)=O.COC1=C(Br)C=C(Br)C=C1OCCC1N(C)CCC1 NRSCVKWUVWTXAD-WLHGVMLRSA-N 0.000 description 2
- FUQJKBLFYYGQHY-UHFFFAOYSA-N 1-cyclohexyl-4-(3,5-dichloro-2-methoxyphenoxy)azepane Chemical compound COC1=C(Cl)C=C(Cl)C=C1OC1CCN(C2CCCCC2)CCC1 FUQJKBLFYYGQHY-UHFFFAOYSA-N 0.000 description 2
- UMPSXRYVXUPCOS-UHFFFAOYSA-N 2,3-dichlorophenol Chemical compound OC1=CC=CC(Cl)=C1Cl UMPSXRYVXUPCOS-UHFFFAOYSA-N 0.000 description 2
- LAONXLSELHLPBP-UHFFFAOYSA-N 2,4-dibromo-6-methoxyphenol Chemical compound COC1=CC(Br)=CC(Br)=C1O LAONXLSELHLPBP-UHFFFAOYSA-N 0.000 description 2
- KWVSBSBWCUGVOW-UHFFFAOYSA-N 2-(2-chloroethyl)-1-(cyclopropylmethyl)pyrrolidine;hydrochloride Chemical compound Cl.ClCCC1CCCN1CC1CC1 KWVSBSBWCUGVOW-UHFFFAOYSA-N 0.000 description 2
- CLVNTYZKUHNUEF-UHFFFAOYSA-N 2-(2-chloroethyl)-1-methylpyrrolidine Chemical compound CN1CCCC1CCCl CLVNTYZKUHNUEF-UHFFFAOYSA-N 0.000 description 2
- SOZROWLDUUKYNG-UHFFFAOYSA-N 2-[2-(3,5-dibromo-2-methoxyphenoxy)ethyl]-1-methylpyrrolidine Chemical compound COC1=C(Br)C=C(Br)C=C1OCCC1N(C)CCC1 SOZROWLDUUKYNG-UHFFFAOYSA-N 0.000 description 2
- BCWXVDIXXWCSTC-UHFFFAOYSA-N 2-[2-(3,5-dichloro-2-ethoxyphenoxy)ethyl]-1-ethylpyrrolidine Chemical compound CCOC1=C(Cl)C=C(Cl)C=C1OCCC1N(CC)CCC1 BCWXVDIXXWCSTC-UHFFFAOYSA-N 0.000 description 2
- LVEYBKZTUVWKHW-UHFFFAOYSA-N 4-(3,5-dichloro-2-methoxyphenoxy)-1-methylazepane Chemical compound COC1=C(Cl)C=C(Cl)C=C1OC1CCN(C)CCC1 LVEYBKZTUVWKHW-UHFFFAOYSA-N 0.000 description 2
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- PCTMTFRHKVHKIS-BMFZQQSSSA-N (1s,3r,4e,6e,8e,10e,12e,14e,16e,18s,19r,20r,21s,25r,27r,30r,31r,33s,35r,37s,38r)-3-[(2r,3s,4s,5s,6r)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-19,25,27,30,31,33,35,37-octahydroxy-18,20,21-trimethyl-23-oxo-22,39-dioxabicyclo[33.3.1]nonatriaconta-4,6,8,10 Chemical compound C1C=C2C[C@@H](OS(O)(=O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2.O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 PCTMTFRHKVHKIS-BMFZQQSSSA-N 0.000 description 1
- YONLFQNRGZXBBF-ZIAGYGMSSA-N (2r,3r)-2,3-dibenzoyloxybutanedioic acid Chemical compound O([C@@H](C(=O)O)[C@@H](OC(=O)C=1C=CC=CC=1)C(O)=O)C(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-ZIAGYGMSSA-N 0.000 description 1
- YONLFQNRGZXBBF-KBPBESRZSA-N (2s,3s)-2,3-dibenzoyloxybutanedioic acid Chemical compound O([C@H](C(=O)O)[C@H](OC(=O)C=1C=CC=CC=1)C(O)=O)C(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-KBPBESRZSA-N 0.000 description 1
- ZDXGQBUWNMFNIU-WLHGVMLRSA-N (e)-but-2-enedioic acid;2-[2-(3,5-dichloro-2-methoxyphenoxy)ethyl]-1-methylpyrrolidine Chemical compound OC(=O)\C=C\C(O)=O.COC1=C(Cl)C=C(Cl)C=C1OCCC1N(C)CCC1 ZDXGQBUWNMFNIU-WLHGVMLRSA-N 0.000 description 1
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 1
- SCSMALNYFAOCHI-UHFFFAOYSA-N 1-(cyclopropylmethyl)-4-(3,5-dichloro-2-methoxyphenoxy)azepane 2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.COC1=C(Cl)C=C(Cl)C=C1OC1CCN(CC2CC2)CCC1 SCSMALNYFAOCHI-UHFFFAOYSA-N 0.000 description 1
- LODFCSFUYRTIDP-UHFFFAOYSA-N 1-cyclohexyl-2-[2-(3,5-dichloro-2-methoxyphenoxy)ethyl]pyrrolidine Chemical compound COC1=C(Cl)C=C(Cl)C=C1OCCC1N(C2CCCCC2)CCC1 LODFCSFUYRTIDP-UHFFFAOYSA-N 0.000 description 1
- SKUOGIHTIMMCRE-UHFFFAOYSA-N 1-cyclohexyl-4-(3,5-dichloro-2-methoxyphenoxy)azepane hydrochloride Chemical compound Cl.COC1=C(Cl)C=C(Cl)C=C1OC1CCN(C2CCCCC2)CCC1 SKUOGIHTIMMCRE-UHFFFAOYSA-N 0.000 description 1
- MEMQECHNVMLWST-UHFFFAOYSA-N 2-(2-chloroethyl)-1-(cyclopropylmethyl)pyrrolidine Chemical compound ClCCC1CCCN1CC1CC1 MEMQECHNVMLWST-UHFFFAOYSA-N 0.000 description 1
- QTZUAGDDMDRZEJ-UHFFFAOYSA-N 2-(2-chloroethyl)-1-cyclohexylpyrrolidine Chemical compound ClCCC1CCCN1C1CCCCC1 QTZUAGDDMDRZEJ-UHFFFAOYSA-N 0.000 description 1
- JYOCTPGVPKYAGP-UHFFFAOYSA-N 2-[2-(3,5-dichloro-2-methoxyphenoxy)ethyl]-1-methylpyrrolidine;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.COC1=C(Cl)C=C(Cl)C=C1OCCC1N(C)CCC1 JYOCTPGVPKYAGP-UHFFFAOYSA-N 0.000 description 1
- LQUOOBUMUREJOX-UHFFFAOYSA-N 2-[2-(3,5-dichlorophenoxy)ethyl]-1-ethylpyrrolidine Chemical compound CCN1CCCC1CCOC1=CC(Cl)=CC(Cl)=C1 LQUOOBUMUREJOX-UHFFFAOYSA-N 0.000 description 1
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- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
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- XXHSVYWKZNGKSD-UHFFFAOYSA-N 4-(3,5-dichloro-2-methoxyphenoxy)-1-methylazepane hydrochloride Chemical compound Cl.COC1=C(Cl)C=C(Cl)C=C1OC1CCN(C)CCC1 XXHSVYWKZNGKSD-UHFFFAOYSA-N 0.000 description 1
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- ZWBBJHBFVVZPDG-UHFFFAOYSA-N CN1CCCC(CC1)OC2=C(C(=CC(=C2)Br)Br)OC Chemical compound CN1CCCC(CC1)OC2=C(C(=CC(=C2)Br)Br)OC ZWBBJHBFVVZPDG-UHFFFAOYSA-N 0.000 description 1
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- AKWLOLHBUORNEW-UHFFFAOYSA-N Cl.C(C)N1C(CCC1)CCOC1=CC(=CC(=C1)Cl)Cl Chemical compound Cl.C(C)N1C(CCC1)CCOC1=CC(=CC(=C1)Cl)Cl AKWLOLHBUORNEW-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
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- 208000027418 Wounds and injury Diseases 0.000 description 1
- ZEEBGORNQSEQBE-UHFFFAOYSA-N [2-(3-phenylphenoxy)-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound C1(=CC(=CC=C1)OC1=NC(=CC(=C1)CN)C(F)(F)F)C1=CC=CC=C1 ZEEBGORNQSEQBE-UHFFFAOYSA-N 0.000 description 1
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- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000008199 coating composition Substances 0.000 description 1
- 229960003920 cocaine Drugs 0.000 description 1
- PIQVDUKEQYOJNR-VZXSFKIWSA-N cocaine hydrochloride Chemical compound [Cl-].O([C@H]1C[C@@H]2CC[C@@H]([NH+]2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 PIQVDUKEQYOJNR-VZXSFKIWSA-N 0.000 description 1
- 229960003771 cocaine hydrochloride Drugs 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000006196 deacetylation Effects 0.000 description 1
- 238000003381 deacetylation reaction Methods 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 150000008049 diazo compounds Chemical class 0.000 description 1
- 229960003887 dichlorophen Drugs 0.000 description 1
- YIDKJPKYCLMJQW-AATRIKPKSA-N diethyl (e)-hex-3-enedioate Chemical compound CCOC(=O)C\C=C\CC(=O)OCC YIDKJPKYCLMJQW-AATRIKPKSA-N 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000005530 etching Methods 0.000 description 1
- HWFPYJUTKGAQAY-UHFFFAOYSA-N ethyl 2-[1-(cyclopropylmethyl)-5-oxopyrrolidin-2-yl]acetate Chemical compound CCOC(=O)CC1CCC(=O)N1CC1CC1 HWFPYJUTKGAQAY-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 210000000245 forearm Anatomy 0.000 description 1
- 239000003193 general anesthetic agent Substances 0.000 description 1
- 244000144993 groups of animals Species 0.000 description 1
- 229960001867 guaiacol Drugs 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 125000006038 hexenyl group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 1
- 229940091173 hydantoin Drugs 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- VRIVJOXICYMTAG-IYEMJOQQSA-L iron(ii) gluconate Chemical compound [Fe+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O VRIVJOXICYMTAG-IYEMJOQQSA-L 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 238000002690 local anesthesia Methods 0.000 description 1
- 229960005015 local anesthetics Drugs 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
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- CEQFOVLGLXCDCX-WUKNDPDISA-N methyl red Chemical compound C1=CC(N(C)C)=CC=C1\N=N\C1=CC=CC=C1C(O)=O CEQFOVLGLXCDCX-WUKNDPDISA-N 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 210000001640 nerve ending Anatomy 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 208000030212 nutrition disease Diseases 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- KYKNRZGSIGMXFH-ZVGUSBNCSA-M potassium bitartrate Chemical compound [K+].OC(=O)[C@H](O)[C@@H](O)C([O-])=O KYKNRZGSIGMXFH-ZVGUSBNCSA-M 0.000 description 1
- 239000001472 potassium tartrate Substances 0.000 description 1
- 229940111695 potassium tartrate Drugs 0.000 description 1
- 235000011005 potassium tartrates Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 210000003497 sciatic nerve Anatomy 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000007790 scraping Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- NESLWCLHZZISNB-UHFFFAOYSA-M sodium phenolate Chemical compound [Na+].[O-]C1=CC=CC=C1 NESLWCLHZZISNB-UHFFFAOYSA-M 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001256 steam distillation Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000002303 tibia Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
-
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D223/08—Oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Neurosurgery (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)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS811017A CS216934B2 (cs) | 1980-07-01 | 1981-02-12 | Způsob výroby l-cyklohexenylmethyl-2-chIorethylpyrrolidinu |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7917610A FR2460935A1 (fr) | 1979-07-06 | 1979-07-06 | Nouvelles phenoxyamines heterocycliques substituees, leur methode de preparation et leur application comme anesthetiques locaux |
| FR8007352A FR2479218A2 (fr) | 1980-04-01 | 1980-04-01 | Nouvelles phenoxyamines heterocycliques substituees, leur methode de preparation et leur application comme anesthesiques locaux |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS216933B2 true CS216933B2 (en) | 1982-12-31 |
Family
ID=26221244
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS804693A CS216933B2 (en) | 1979-07-06 | 1980-07-01 | Method of making the heterocyclic phenoxyemines |
Country Status (37)
| Country | Link |
|---|---|
| US (1) | US4379161A (da) |
| EP (2) | EP0094102B1 (da) |
| JP (2) | JPS5639065A (da) |
| AR (1) | AR224012A1 (da) |
| AT (2) | ATE10739T1 (da) |
| AU (2) | AU536482B2 (da) |
| BE (1) | BE884124A (da) |
| BG (2) | BG35746A3 (da) |
| CA (1) | CA1163273A (da) |
| CH (2) | CH648827A5 (da) |
| CS (1) | CS216933B2 (da) |
| DD (2) | DD201141A5 (da) |
| DE (2) | DE3069789D1 (da) |
| DK (1) | DK157538C (da) |
| ES (1) | ES8103049A1 (da) |
| FI (2) | FI74274C (da) |
| GR (1) | GR69638B (da) |
| HK (2) | HK55689A (da) |
| HU (2) | HU181147B (da) |
| IE (2) | IE50061B1 (da) |
| IL (2) | IL60472A (da) |
| IN (2) | IN153037B (da) |
| IT (1) | IT1188985B (da) |
| JO (1) | JO1077B1 (da) |
| LU (1) | LU82584A1 (da) |
| MA (1) | MA18893A1 (da) |
| MX (2) | MX6366E (da) |
| NO (2) | NO156086C (da) |
| NZ (1) | NZ194230A (da) |
| OA (1) | OA06561A (da) |
| PH (1) | PH16449A (da) |
| PL (1) | PL127393B1 (da) |
| PT (1) | PT71482A (da) |
| RO (2) | RO85323B (da) |
| SU (1) | SU1085507A3 (da) |
| YU (2) | YU42344B (da) |
| ZW (1) | ZW15280A1 (da) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2586018B1 (fr) * | 1985-08-12 | 1988-03-25 | Ile De France | Nouveau benzodioxepanne, son procede de synthese et ses applications en therapeutique |
| AU5358490A (en) * | 1989-04-07 | 1990-11-05 | Fujisawa Pharmaceutical Co., Ltd. | New naphthalene compounds and method of producing the same |
| EP0471941A3 (en) * | 1990-08-16 | 1992-10-14 | American Cyanamid Company | An improved process for the preparation of 5-bromo-2-methoxyresorcinol |
| US5472958A (en) * | 1994-08-29 | 1995-12-05 | Abbott Laboratories | 2-((nitro)phenoxymethyl) heterocyclic compounds that enhance cognitive function |
| US7799337B2 (en) | 1997-07-21 | 2010-09-21 | Levin Bruce H | Method for directed intranasal administration of a composition |
| ATE247104T1 (de) * | 1997-11-05 | 2003-08-15 | Neurosearch As | Azaring-ether-derivate und ihre verwendung als nicotinic-ach-rezeptormodulatoren |
| US8473062B2 (en) * | 2008-05-01 | 2013-06-25 | Autonomic Technologies, Inc. | Method and device for the treatment of headache |
| US8412336B2 (en) * | 2008-12-29 | 2013-04-02 | Autonomic Technologies, Inc. | Integrated delivery and visualization tool for a neuromodulation system |
| US8494641B2 (en) * | 2009-04-22 | 2013-07-23 | Autonomic Technologies, Inc. | Implantable neurostimulator with integral hermetic electronic enclosure, circuit substrate, monolithic feed-through, lead assembly and anchoring mechanism |
| US9320908B2 (en) * | 2009-01-15 | 2016-04-26 | Autonomic Technologies, Inc. | Approval per use implanted neurostimulator |
| US20100185249A1 (en) * | 2009-01-22 | 2010-07-22 | Wingeier Brett M | Method and Devices for Adrenal Stimulation |
| CN111205015B (zh) * | 2020-01-20 | 2021-11-26 | 东南大学 | 一种高稳定泡沫混凝土发泡剂的制备方法 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE543876C (de) * | 1928-04-25 | 1932-02-11 | C H Boehringer Sohn Akt Ges | Verfahren zur Darstellung von Piperidinalkinen |
| US3117976A (en) * | 1958-11-12 | 1964-01-14 | Beecham Res Lab | Nu-alkyl-pyrrolidine-2-methanol, alpha cyclohexyl mandelates |
| FR1342756A (fr) * | 1958-11-21 | 1963-11-15 | Beecham Res Lab | Esters basiques et leur procédé de préparation, notamment le phényl-cyclohexyl-glycolate de (1-méthyl-2-pyrrolidyl) méthyle et ses sels d'addition |
| GB1096441A (en) * | 1964-01-15 | 1967-12-29 | Bristol Myers Co | Ethers of benzyl phenols and a process for the preparation thereof |
| US3904622A (en) * | 1968-02-16 | 1975-09-09 | Ile De France | Dialkylaminoalkyl ethers of 2-alkoxy-3,5-dihalobenzene |
| GB1268951A (en) * | 1969-06-12 | 1972-03-29 | Pfizer Ltd | Phenoxy-amines |
| FR2155927A1 (en) * | 1971-10-15 | 1973-05-25 | Synthelabo | 1-phenylcyclo hexane carboxylic acid esters - with antispasmodic and anticholinergic activity |
| JPS5139661A (en) * | 1974-09-27 | 1976-04-02 | Nippon Kayaku Kk | Kogakukatsusei 11 mechiru 22 * beetaaa hidorokishechiru * pirorijin oyobisono chukantaino seizoho |
| JPS5251362A (en) * | 1975-10-20 | 1977-04-25 | Teijin Ltd | Preparation of optically active pyrrolidine derivatives |
| LU78625A1 (de) * | 1977-12-02 | 1979-06-13 | Byk Gulden Lomberg Chem Fab | Substituierte 1-phenyl-2-pyrrolidin-2-yl-ethanole,verfahren zu ihrer herstellung,ihre verwendung und sie enthaltende arzneimittel |
| DE2811952A1 (de) * | 1978-03-18 | 1979-10-31 | Merck Patent Gmbh | Phenoxyalkylamine und verfahren zu ihrer herstellung |
-
1980
- 1980-06-25 US US06/162,796 patent/US4379161A/en not_active Expired - Lifetime
- 1980-07-01 SU SU802938255A patent/SU1085507A3/ru active
- 1980-07-01 AT AT80400999T patent/ATE10739T1/de not_active IP Right Cessation
- 1980-07-01 DE DE8080400999T patent/DE3069789D1/de not_active Expired
- 1980-07-01 EP EP83105420A patent/EP0094102B1/fr not_active Expired
- 1980-07-01 DE DE8383105420T patent/DE3071314D1/de not_active Expired
- 1980-07-01 CS CS804693A patent/CS216933B2/cs unknown
- 1980-07-01 BG BG8362115A patent/BG35746A3/xx unknown
- 1980-07-01 BG BG8048341A patent/BG35039A3/xx unknown
- 1980-07-01 AT AT83105420T patent/ATE17119T1/de not_active IP Right Cessation
- 1980-07-01 YU YU1710/80A patent/YU42344B/xx unknown
- 1980-07-01 EP EP80400999A patent/EP0024960B1/fr not_active Expired
- 1980-07-01 OA OA57149A patent/OA06561A/xx unknown
- 1980-07-02 PT PT71482A patent/PT71482A/pt unknown
- 1980-07-02 AU AU60028/80A patent/AU536482B2/en not_active Ceased
- 1980-07-02 IL IL60472A patent/IL60472A/xx unknown
- 1980-07-02 BE BE1/9873A patent/BE884124A/fr not_active IP Right Cessation
- 1980-07-03 HU HU80801658A patent/HU181147B/hu not_active IP Right Cessation
- 1980-07-03 AR AR281635A patent/AR224012A1/es active
- 1980-07-03 RO RO110029A patent/RO85323B/ro unknown
- 1980-07-03 HU HU822217A patent/HU186539B/hu not_active IP Right Cessation
- 1980-07-03 NZ NZ194230A patent/NZ194230A/xx unknown
- 1980-07-03 RO RO101590A patent/RO81532B/ro unknown
- 1980-07-04 ES ES493111A patent/ES8103049A1/es not_active Expired
- 1980-07-04 IE IE1653/85A patent/IE50061B1/en not_active IP Right Cessation
- 1980-07-04 NO NO802027A patent/NO156086C/no unknown
- 1980-07-04 IT IT49163/80A patent/IT1188985B/it active
- 1980-07-04 CH CH5169/80A patent/CH648827A5/fr not_active IP Right Cessation
- 1980-07-04 PL PL1980225473A patent/PL127393B1/pl unknown
- 1980-07-04 MX MX80100439U patent/MX6366E/es unknown
- 1980-07-04 ZW ZW152/80A patent/ZW15280A1/xx unknown
- 1980-07-04 CH CH5684/84A patent/CH655100A5/fr not_active IP Right Cessation
- 1980-07-04 MA MA19091A patent/MA18893A1/fr unknown
- 1980-07-04 IE IE1392/80A patent/IE50060B1/en not_active IP Right Cessation
- 1980-07-04 FI FI802156A patent/FI74274C/fi not_active IP Right Cessation
- 1980-07-04 LU LU82584A patent/LU82584A1/fr unknown
- 1980-07-04 GR GR62381A patent/GR69638B/el unknown
- 1980-07-04 DK DK289580A patent/DK157538C/da not_active IP Right Cessation
- 1980-07-04 MX MX8011334U patent/MX7642E/es unknown
- 1980-07-05 JO JO19801077A patent/JO1077B1/en active
- 1980-07-05 IN IN779/CAL/80A patent/IN153037B/en unknown
- 1980-07-07 DD DD80234984A patent/DD201141A5/de not_active IP Right Cessation
- 1980-07-07 PH PH24248A patent/PH16449A/en unknown
- 1980-07-07 JP JP9321680A patent/JPS5639065A/ja active Granted
- 1980-07-07 DD DD222455A patent/DD153206A5/de unknown
- 1980-09-30 JP JP13751280A patent/JPS5649351A/ja active Granted
-
1982
- 1982-12-16 CA CA000417963A patent/CA1163273A/fr not_active Expired
- 1982-12-17 YU YU2801/82A patent/YU42824B/xx unknown
-
1983
- 1983-06-01 IL IL68854A patent/IL68854A0/xx not_active IP Right Cessation
- 1983-10-10 IN IN1246/CAL/83A patent/IN158706B/en unknown
-
1984
- 1984-03-02 AU AU25260/84A patent/AU563009B2/en not_active Ceased
-
1986
- 1986-05-20 NO NO861988A patent/NO861988L/no unknown
-
1987
- 1987-07-03 FI FI872955A patent/FI872955A0/fi not_active Application Discontinuation
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1989
- 1989-07-13 HK HK556/89A patent/HK55689A/xx unknown
- 1989-07-13 HK HK558/89A patent/HK55889A/xx unknown
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