NL192201C - Farmacologisch actieve fenylaminoalkylcyclobutaanverbindingen en preparaten die deze verbindingen bevatten. - Google Patents

Farmacologisch actieve fenylaminoalkylcyclobutaanverbindingen en preparaten die deze verbindingen bevatten. Download PDF

Info

Publication number: NL192201C
Authority: NL; Netherlands
Prior art keywords: formula; ether; mixture; group; cyclobutyl
Prior art date: 1981-04-06

Application number

NL8201347A

Other languages

English (en)

Dutch (nl)

Other versions

NL8201347A (nl

NL192201B (nl

Original Assignee

Knoll Ag

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1981-04-06

Filing date

1982-03-31

Publication date

1997-03-04

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26279045&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=NL192201(C) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1982-03-31 Application filed by Knoll Ag filed Critical Knoll Ag

1982-11-01 Publication of NL8201347A publication Critical patent/NL8201347A/nl

1996-11-01 Publication of NL192201B publication Critical patent/NL192201B/xx

1997-03-04 Application granted granted Critical

1997-03-04 Publication of NL192201C publication Critical patent/NL192201C/nl

Links

150000001875 compounds Chemical class 0.000 title claims description 125
238000002360 preparation method Methods 0.000 title description 10
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 364
VEXZGXHMUGYJMC-UHFFFAOYSA-N hydrochloric acid Substances Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 158
239000000203 mixture Substances 0.000 claims description 142
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 128
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 84
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 56
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 51
125000004432 carbon atom Chemical group C* 0.000 claims description 47
-1 lithium aluminum hydride Chemical compound 0.000 claims description 46
239000011541 reaction mixture Substances 0.000 claims description 40
125000001309 chloro group Chemical group Cl* 0.000 claims description 37
239000000047 product Substances 0.000 claims description 35
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 32
239000012259 ether extract Substances 0.000 claims description 31
125000000217 alkyl group Chemical group 0.000 claims description 30
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 28
235000019253 formic acid Nutrition 0.000 claims description 28
239000012265 solid product Substances 0.000 claims description 27
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 25
229910052757 nitrogen Inorganic materials 0.000 claims description 22
238000002844 melting Methods 0.000 claims description 20
230000008018 melting Effects 0.000 claims description 20
125000004433 nitrogen atom Chemical group N* 0.000 claims description 19
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 18
229910000041 hydrogen chloride Inorganic materials 0.000 claims description 18
239000012280 lithium aluminium hydride Substances 0.000 claims description 18
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
238000010992 reflux Methods 0.000 claims description 18
229910052739 hydrogen Inorganic materials 0.000 claims description 17
239000001257 hydrogen Substances 0.000 claims description 17
150000001408 amides Chemical class 0.000 claims description 16
238000001816 cooling Methods 0.000 claims description 16
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 14
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
125000000753 cycloalkyl group Chemical group 0.000 claims description 13
239000007789 gas Substances 0.000 claims description 13
239000012299 nitrogen atmosphere Substances 0.000 claims description 13
230000002829 reductive effect Effects 0.000 claims description 11
150000003839 salts Chemical class 0.000 claims description 10
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
125000001424 substituent group Chemical group 0.000 claims description 9
125000003342 alkenyl group Chemical group 0.000 claims description 8
239000000725 suspension Substances 0.000 claims description 8
125000004429 atom Chemical group 0.000 claims description 7
125000003545 alkoxy group Chemical group 0.000 claims description 6
230000001430 anti-depressive effect Effects 0.000 claims description 6
239000008346 aqueous phase Substances 0.000 claims description 6
239000000706 filtrate Substances 0.000 claims description 6
125000005843 halogen group Chemical group 0.000 claims description 6
125000000304 alkynyl group Chemical group 0.000 claims description 5
125000000623 heterocyclic group Chemical group 0.000 claims description 5
230000009471 action Effects 0.000 claims description 4
239000000935 antidepressant agent Substances 0.000 claims description 4
229910052799 carbon Inorganic materials 0.000 claims description 4
125000005842 heteroatom Chemical group 0.000 claims description 4
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 3
239000003610 charcoal Substances 0.000 claims description 3
125000000068 chlorophenyl group Chemical group 0.000 claims description 3
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
ZLKJNMVOEPFJJY-UHFFFAOYSA-N 2-[1-(4-chlorophenyl)cyclobutyl]acetic acid Chemical compound C=1C=C(Cl)C=CC=1C1(CC(=O)O)CCC1 ZLKJNMVOEPFJJY-UHFFFAOYSA-N 0.000 claims description 2
239000004280 Sodium formate Substances 0.000 claims description 2
125000004414 alkyl thio group Chemical group 0.000 claims description 2
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
XWBDWHCCBGMXKG-UHFFFAOYSA-N ethanamine;hydron;chloride Chemical compound Cl.CCN XWBDWHCCBGMXKG-UHFFFAOYSA-N 0.000 claims description 2
239000008194 pharmaceutical composition Substances 0.000 claims description 2
230000000144 pharmacologic effect Effects 0.000 claims description 2
HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 claims description 2
235000019254 sodium formate Nutrition 0.000 claims description 2
HFURRFQQRVYYNK-UHFFFAOYSA-N 2-[1-(4-chlorophenyl)cyclobutyl]-n-cyclopropylacetamide Chemical compound C1=CC(Cl)=CC=C1C1(CC(=O)NC2CC2)CCC1 HFURRFQQRVYYNK-UHFFFAOYSA-N 0.000 claims 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 claims 1
239000005862 Whey Substances 0.000 claims 1
102000007544 Whey Proteins Human genes 0.000 claims 1
108010046377 Whey Proteins Proteins 0.000 claims 1
ZLNQPKAFXRAIMD-UHFFFAOYSA-N n-[2-[1-(4-chlorophenyl)cyclobutyl]ethyl]-n-methylcyclopropanamine;hydrochloride Chemical compound Cl.C1CC1N(C)CCC1(C=2C=CC(Cl)=CC=2)CCC1 ZLNQPKAFXRAIMD-UHFFFAOYSA-N 0.000 claims 1
239000000126 substance Substances 0.000 claims 1
239000000243 solution Substances 0.000 description 107
239000000460 chlorine Substances 0.000 description 72
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
238000006243 chemical reaction Methods 0.000 description 33
150000002576 ketones Chemical class 0.000 description 30
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 27
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 26
239000002253 acid Substances 0.000 description 26
MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 25
239000003921 oil Substances 0.000 description 23
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
239000003208 petroleum Substances 0.000 description 21
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 19
239000000284 extract Substances 0.000 description 19
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
238000009835 boiling Methods 0.000 description 18
150000001299 aldehydes Chemical class 0.000 description 17
125000004093 cyano group Chemical group *C#N 0.000 description 17
238000001704 evaporation Methods 0.000 description 17
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 16
230000008020 evaporation Effects 0.000 description 16
OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 16
230000009467 reduction Effects 0.000 description 16
238000006722 reduction reaction Methods 0.000 description 16
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 15
150000003335 secondary amines Chemical class 0.000 description 15
150000001412 amines Chemical class 0.000 description 13
239000002585 base Substances 0.000 description 13
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 13
150000001732 carboxylic acid derivatives Chemical class 0.000 description 13
239000003153 chemical reaction reagent Substances 0.000 description 13
239000011928 denatured alcohol Substances 0.000 description 13
125000002524 organometallic group Chemical group 0.000 description 13
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 12
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 11
229910052801 chlorine Inorganic materials 0.000 description 11
150000001805 chlorine compounds Chemical class 0.000 description 11
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 11
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 10
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
239000005909 Kieselgur Substances 0.000 description 10
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
230000007062 hydrolysis Effects 0.000 description 10
238000006460 hydrolysis reaction Methods 0.000 description 10
229910052740 iodine Inorganic materials 0.000 description 10
238000000034 method Methods 0.000 description 10
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 10
150000003141 primary amines Chemical class 0.000 description 10
239000007787 solid Substances 0.000 description 10
238000003756 stirring Methods 0.000 description 10
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 9
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
229910052794 bromium Inorganic materials 0.000 description 9
238000004821 distillation Methods 0.000 description 9
239000011777 magnesium Substances 0.000 description 9
229910052749 magnesium Inorganic materials 0.000 description 9
239000012279 sodium borohydride Substances 0.000 description 9
229910000033 sodium borohydride Inorganic materials 0.000 description 9
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 8
LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 8
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 8
150000001735 carboxylic acids Chemical class 0.000 description 8
239000003638 chemical reducing agent Substances 0.000 description 8
150000002466 imines Chemical class 0.000 description 8
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 8
238000005406 washing Methods 0.000 description 8
CTKUIZGFDSJHPY-UHFFFAOYSA-N 1-(3,4-dichlorophenyl)cyclobutane-1-carbonitrile Chemical compound C1=C(Cl)C(Cl)=CC=C1C1(C#N)CCC1 CTKUIZGFDSJHPY-UHFFFAOYSA-N 0.000 description 7
MDPJGCZTXIAMEF-UHFFFAOYSA-N 1-[1-(3,4-dichlorophenyl)cyclobutyl]ethanone Chemical compound C=1C=C(Cl)C(Cl)=CC=1C1(C(=O)C)CCC1 MDPJGCZTXIAMEF-UHFFFAOYSA-N 0.000 description 7
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 7
239000012458 free base Substances 0.000 description 7
150000003840 hydrochlorides Chemical class 0.000 description 7
239000002904 solvent Substances 0.000 description 7
150000003512 tertiary amines Chemical class 0.000 description 7
DDUHZTYCFQRHIY-UHFFFAOYSA-N 7-chloro-3',4,6-trimethoxy-5'-methylspiro[1-benzofuran-2,4'-cyclohex-2-ene]-1',3-dione Chemical compound COC1=CC(=O)CC(C)C11C(=O)C(C(OC)=CC(OC)=C2Cl)=C2O1 DDUHZTYCFQRHIY-UHFFFAOYSA-N 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
241000699670 Mus sp. Species 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
239000007864 aqueous solution Substances 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
238000001035 drying Methods 0.000 description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
150000004795 grignard reagents Chemical class 0.000 description 6
TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical compound COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
150000002900 organolithium compounds Chemical class 0.000 description 6
239000012071 phase Substances 0.000 description 6
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 6
ITTUENTZMNXAAF-UHFFFAOYSA-N 1-[1-(3,4-dichlorophenyl)cyclobutyl]butan-2-one Chemical compound C=1C=C(Cl)C(Cl)=CC=1C1(CC(=O)CC)CCC1 ITTUENTZMNXAAF-UHFFFAOYSA-N 0.000 description 5
OEYNIBRJHDKARY-UHFFFAOYSA-N 2-[1-(4-chlorophenyl)cyclobutyl]acetonitrile Chemical compound C1=CC(Cl)=CC=C1C1(CC#N)CCC1 OEYNIBRJHDKARY-UHFFFAOYSA-N 0.000 description 5
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
125000006193 alkinyl group Chemical group 0.000 description 5
230000029936 alkylation Effects 0.000 description 5
238000005804 alkylation reaction Methods 0.000 description 5
229910021529 ammonia Inorganic materials 0.000 description 5
150000002148 esters Chemical class 0.000 description 5
229910052731 fluorine Inorganic materials 0.000 description 5
239000000463 material Substances 0.000 description 5
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
239000012258 stirred mixture Substances 0.000 description 5
XQONXPWVIZZJIL-UHFFFAOYSA-N 1-(4-chlorophenyl)cyclobutane-1-carbonitrile Chemical compound C1=CC(Cl)=CC=C1C1(C#N)CCC1 XQONXPWVIZZJIL-UHFFFAOYSA-N 0.000 description 4
CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 4
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
239000007818 Grignard reagent Substances 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
150000001350 alkyl halides Chemical class 0.000 description 4
GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 4
HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 4
239000013078 crystal Substances 0.000 description 4
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 4
AVKNGPAMCBSNSO-UHFFFAOYSA-N cyclohexylmethanamine Chemical compound NCC1CCCCC1 AVKNGPAMCBSNSO-UHFFFAOYSA-N 0.000 description 4
150000003948 formamides Chemical class 0.000 description 4
238000010438 heat treatment Methods 0.000 description 4
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
229910052744 lithium Inorganic materials 0.000 description 4
229910052751 metal Inorganic materials 0.000 description 4
239000002184 metal Substances 0.000 description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
239000008096 xylene Substances 0.000 description 4
SGEOBUJTURUUJE-UHFFFAOYSA-N (6-propan-2-yloxypyridin-3-yl)boronic acid Chemical compound CC(C)OC1=CC=C(B(O)O)C=N1 SGEOBUJTURUUJE-UHFFFAOYSA-N 0.000 description 3
NVKSHKBLPQLFKG-UHFFFAOYSA-N 1-[1-(3,4-dichlorophenyl)cyclobutyl]ethanamine Chemical compound C=1C=C(Cl)C(Cl)=CC=1C1(C(N)C)CCC1 NVKSHKBLPQLFKG-UHFFFAOYSA-N 0.000 description 3
XPOVVLMSMQCITO-UHFFFAOYSA-N 1-[1-(4-chlorophenyl)cyclobutyl]propan-2-one Chemical compound C=1C=C(Cl)C=CC=1C1(CC(=O)C)CCC1 XPOVVLMSMQCITO-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 3
239000005695 Ammonium acetate Substances 0.000 description 3
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 3
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 3
QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
235000019257 ammonium acetate Nutrition 0.000 description 3
229940043376 ammonium acetate Drugs 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
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- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
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- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/02—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
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- A61P25/24—Antidepressants
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- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
- C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
- C07C29/147—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of carboxylic acids or derivatives thereof
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- 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
- C07D207/06—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 radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms
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- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
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- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/70—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
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- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/06—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by halogen atoms or nitro radicals
- C07D295/073—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by halogen atoms or nitro radicals with the ring nitrogen atoms and the substituents separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Engineering & Computer Science (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Psychiatry (AREA)
Bioinformatics & Cheminformatics (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pain & Pain Management (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Hydrogenated Pyridines (AREA)

NL8201347A 1981-04-06 1982-03-31 Farmacologisch actieve fenylaminoalkylcyclobutaanverbindingen en preparaten die deze verbindingen bevatten. NL192201C (nl)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
GB8110709		1981-04-06
GB8110709		1981-04-06
GB8110710		1981-04-06
GB8110710		1981-04-06

Publications (3)

Publication Number	Publication Date
NL8201347A NL8201347A (nl)	1982-11-01
NL192201B NL192201B (nl)	1996-11-01
NL192201C true NL192201C (nl)	1997-03-04

Family

ID=26279045

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NL8201347A NL192201C (nl)	1981-04-06	1982-03-31	Farmacologisch actieve fenylaminoalkylcyclobutaanverbindingen en preparaten die deze verbindingen bevatten.

Country Status (40)

Country	Link
KR (1)	KR900000274B1 (uk)
AT (1)	AT382612B (uk)
AU (1)	AU545595B2 (uk)
BG (2)	BG40652A3 (uk)
CA (1)	CA1248955A (uk)
CH (1)	CH652117A5 (uk)
CS (1)	CS244672B2 (uk)
CY (1)	CY1408A (uk)
DD (1)	DD208348A5 (uk)
DE (1)	DE3212682A1 (uk)
DK (1)	DK161770C (uk)
ES (5)	ES511152A0 (uk)
FI (1)	FI77223C (uk)
FR (1)	FR2504920B1 (uk)
GB (1)	GB2098602B (uk)
GE (1)	GEP19970661B (uk)
GR (1)	GR76697B (uk)
HK (1)	HK13888A (uk)
HU (1)	HU186582B (uk)
IE (1)	IE52768B1 (uk)
IL (1)	IL65257A0 (uk)
IN (1)	IN155773B (uk)
IT (1)	IT1235758B (uk)
JO (1)	JO1184B1 (uk)
KE (1)	KE3753A (uk)
LU (1)	LU84070A1 (uk)
MY (1)	MY8800048A (uk)
NL (1)	NL192201C (uk)
NO (1)	NO156785C (uk)
NZ (1)	NZ200178A (uk)
PH (1)	PH22762A (uk)
PL (2)	PL136242B1 (uk)
PT (1)	PT74580B (uk)
RO (2)	RO89436A2 (uk)
SE (1)	SE452611B (uk)
SG (1)	SG67287G (uk)
SU (2)	SU1482522A3 (uk)
UA (2)	UA7838A1 (uk)
YU (2)	YU44336B (uk)
ZW (1)	ZW4982A1 (uk)

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IE56001B1 (en) *	1982-09-30	1991-03-13	Boots Co Plc	1-arylcyclobutylmethylamine compounds
GB8412480D0 (en) *	1984-05-16	1984-06-20	Elliott M	Pesticides
DK58285D0 (da) *	1984-05-30	1985-02-08	Novo Industri As	Peptider samt fremstilling og anvendelse deraf
GB8501192D0 (en) *	1985-01-17	1985-02-20	Boots Co Plc	Therapeutic agents
DK119785D0 (da) *	1985-03-15	1985-03-15	Nordisk Gentofte	Insulinpraeparat
US5157021A (en) *	1985-03-15	1992-10-20	Novo Nordisk A/S	Insulin derivatives and pharmaceutical preparations containing these derivatives
GB8531071D0 (en) *	1985-12-17	1986-01-29	Boots Co Plc	Therapeutic compound
GB2184122B (en) *	1985-12-17	1989-10-18	Boots Co Plc	N,n-dimethyl-1-[1-(4-chlorophenyl)cyclobutyl]-3-methyl butylamine hydrochloride monohydrate
GB8704777D0 (en) *	1987-02-28	1987-04-01	Boots Co Plc	Medical treatment
JP2675573B2 (ja) *	1988-03-31	1997-11-12	科研製薬株式会社	脳機能改善剤
WO1994000114A1 (en) *	1992-06-23	1994-01-06	Sepracor Inc.	Methods and compositions for treating depression and other disorders using optically pure (-) sibutramine
GB9309749D0 (en) *	1993-05-12	1993-06-23	Boots Co Plc	Therapeutic agents
US5459164A (en) *	1994-02-03	1995-10-17	Boots Pharmaceuticals, Inc.	Medical treatment
DE19518988A1 (de) *	1995-05-29	1996-12-05	Basf Ag	Verwendung arylsubstituierter Cyclobutylalkylamine zur Behandlung der Fettleibigkeit
GB9524681D0 (en)	1995-12-02	1996-01-31	Knoll Ag	Chemical process
GB9619757D0 (en) *	1996-09-21	1996-11-06	Knoll Ag	Chemical process
GB9619962D0 (en) *	1996-09-25	1996-11-13	Knoll Ag	Medical treatment
GB9619961D0 (en) *	1996-09-25	1996-11-13	Knoll Ag	Medical treatment
GB9727131D0 (en)	1997-12-24	1998-02-25	Knoll Ag	Therapeutic agents
AU2007200334B8 (en) *	1998-08-24	2010-10-21	Sepracor, Inc.	Methods of using and compositions comprising dopamine reuptake inhibitors
US6339106B1 (en)	1999-08-11	2002-01-15	Sepracor, Inc.	Methods and compositions for the treatment and prevention of sexual dysfunction
US6974838B2 (en)	1998-08-24	2005-12-13	Sepracor Inc.	Methods of treating or preventing pain using sibutramine metabolites
US6331571B1 (en) *	1998-08-24	2001-12-18	Sepracor, Inc.	Methods of treating and preventing attention deficit disorders
US6476078B2 (en)	1999-08-11	2002-11-05	Sepracor, Inc.	Methods of using sibutramine metabolites in combination with a phosphodiesterase inhibitor to treat sexual dysfunction
BG65170B1 (bg) *	1999-03-17	2007-05-31	Knoll Gmbh	Използване на n-заместени производни на 1-[1-(4-хлорофенил)циклобутил]-3-метилбутиламин за производство на лекарство за лечение на разстройства при храненето
US6552087B1 (en)	1999-03-19	2003-04-22	Abbott Gmbh & Co. Kg	Therapeutic agent comprising (+)-sibutramine
GB9915617D0 (en)	1999-07-05	1999-09-01	Knoll Ag	Therapeutic agents
US6399826B1 (en)	1999-08-11	2002-06-04	Sepracor Inc.	Salts of sibutramine metabolites, methods of making sibutramine metabolites and intermediates useful in the same, and methods of treating pain
RU2238084C2 (ru) *	1999-08-11	2004-10-20	Сепракор Инк.	Композиции, содержащие ингибиторы обратного захвата допамина, и способы их применения
WO2002036540A2 (en) *	2000-11-02	2002-05-10	Torrent Pharmaceuticals Ltd	PROCESS FOR PREPARATION OF β-PHENETHYLAMINE DERIVATIVE
WO2002083631A1 (en)	2001-04-13	2002-10-24	Sepracor Inc.	Methods of preparing didesmethylsibutramine and other sibutramine derivatives
KR100536750B1 (ko) *	2002-10-05	2005-12-16	한미약품 주식회사	시부트라민 메탄술폰산염의 결정성 반수화물을 포함하는약학 조성물
FR2870537A1 (fr) *	2004-05-19	2005-11-25	Servier Lab	Nouveau procede de synthese du (1s)-4,5-dimethoxy-1-(methyl aminomethyl-)-benzocyclobutane et de ses sels d'addition, et application a la synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable
KR100606533B1 (ko)	2004-08-27	2006-08-01	한올제약주식회사	시부트라민의 개선된 합성방법
KR100606534B1 (ko)	2004-11-01	2006-08-01	한올제약주식회사	생산성을 향상시킨 시부트라민의 개선된 합성방법
KR100618176B1 (ko) *	2004-12-02	2006-09-01	휴먼팜 주식회사	시부트라민 주석산염, 이의 제조 방법 및 이를 포함하는약학적 조성물
EP1846359A4 (en)	2005-01-06	2010-03-31	Cj Cheiljedang Corp	INORGANIC ACID SALTS OF SIBUTRAMINE
US7989500B2 (en)	2006-09-15	2011-08-02	Reviva Pharmaceuticals, Inc.	Synthesis, methods of using, and compositions of cycloalkylmethylamines
CN101555214B (zh) *	2008-04-08	2012-07-11	北京嘉事联博医药科技有限公司	苯基环丁基酰胺衍生物及其光学异构体、制备方法和用途
FR2935381B1 (fr) *	2008-08-29	2010-12-17	Servier Lab	Nouveau procede de resolution des enantiomerees du (3,4-dimethoxy-bicyclo°4.2.0!octa-1,3,5-trien-7-yl)nitrile et application a la synthese de l'ivabradine
WO2010082216A2 (en) *	2008-12-08	2010-07-22	Matrix Laboratories Ltd	Novel salts of sibutramine and their crystal forms
HRP20150107T1 (xx)	2009-11-02	2015-03-13	Pfizer Inc.	Derivati dioksabiciklo[3.2.1]oktan-2,3,4-triola
WO2012003501A2 (en)	2010-07-02	2012-01-05	Reviva Pharmaceuticals, Inc.	Compositions, synthesis, and methods of using cycloalkylmethylamine derivatives
JP2015507635A (ja) *	2011-12-30	2015-03-12	レビバファーマシューティカルズ，インコーポレイティド	組成物、合成およびフェニルシクロアルキルメチルアミン誘導体を使用する方法
FR2993561B1 (fr) *	2012-07-17	2014-10-31	Servier Lab	Procede de synthese enzymatique de la (7s)-1-(3,4-dimethoxy bicyclo[4.2.0]octa-1,3,5-triene 7-yl) n-methyl methanamine, et application a la synthese de l'ivabradine et de ses sels

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DE1124485B (de) *	1960-02-12	1962-03-01	Hoechst Ag	Verfahren zur Herstellung von analeptisch wirksamen Phenylcycloalkylmethylaminen
US3526656A (en) *	1967-05-25	1970-09-01	Parke Davis & Co	(1-arylcyclobutyl)carbonyl carbamic acid derivatives

1982
- 1982-03-03 IE IE481/82A patent/IE52768B1/en active Protection Beyond IP Right Term
- 1982-03-15 IL IL65257A patent/IL65257A0/xx unknown
- 1982-03-15 PT PT74580A patent/PT74580B/pt unknown
- 1982-03-16 PH PH27003A patent/PH22762A/en unknown
- 1982-03-16 ZW ZW49/82A patent/ZW4982A1/xx unknown
- 1982-03-30 NZ NZ200178A patent/NZ200178A/en unknown
- 1982-03-31 DK DK146482A patent/DK161770C/da not_active IP Right Cessation
- 1982-03-31 CA CA000400146A patent/CA1248955A/en not_active Expired
- 1982-03-31 AU AU82213/82A patent/AU545595B2/en not_active Expired
- 1982-03-31 NO NO821087A patent/NO156785C/no not_active IP Right Cessation
- 1982-03-31 NL NL8201347A patent/NL192201C/nl not_active IP Right Cessation
- 1982-04-01 GB GB8209591A patent/GB2098602B/en not_active Expired
- 1982-04-01 RO RO82114421A patent/RO89436A2/ro unknown
- 1982-04-01 CY CY140882A patent/CY1408A/en unknown
- 1982-04-01 CH CH2020/82A patent/CH652117A5/fr not_active IP Right Cessation
- 1982-04-01 RO RO107119A patent/RO84802B/ro unknown
- 1982-04-01 FR FR8205634A patent/FR2504920B1/fr not_active Expired
- 1982-04-02 AT AT0132582A patent/AT382612B/de not_active IP Right Cessation
- 1982-04-02 YU YU750/82A patent/YU44336B/xx unknown
- 1982-04-02 IT IT8248157A patent/IT1235758B/it active
- 1982-04-05 HU HU821040A patent/HU186582B/hu unknown
- 1982-04-05 SU SU823426748A patent/SU1482522A3/ru active
- 1982-04-05 FI FI821197A patent/FI77223C/fi not_active IP Right Cessation
- 1982-04-05 SE SE8202166A patent/SE452611B/sv not_active IP Right Cessation
- 1982-04-05 UA UA3426748A patent/UA7838A1/uk unknown
- 1982-04-05 UA UA3834158A patent/UA7589A1/uk unknown
- 1982-04-05 JO JO19821184A patent/JO1184B1/en active
- 1982-04-05 GR GR67812A patent/GR76697B/el unknown
- 1982-04-05 IN IN383/CAL/82A patent/IN155773B/en unknown
- 1982-04-05 LU LU84070A patent/LU84070A1/fr unknown
- 1982-04-05 ES ES511152A patent/ES511152A0/es active Granted
- 1982-04-05 DE DE19823212682 patent/DE3212682A1/de active Granted
- 1982-04-06 KR KR828201506A patent/KR900000274B1/ko not_active Expired
- 1982-04-06 CS CS822457A patent/CS244672B2/cs unknown
- 1982-04-06 BG BG060417A patent/BG40652A3/xx unknown
- 1982-04-06 PL PL1982240079A patent/PL136242B1/pl unknown
- 1982-04-06 PL PL1982235832A patent/PL139120B1/pl unknown
- 1982-04-06 BG BG056100A patent/BG40651A3/xx unknown
- 1982-04-06 DD DD82238787A patent/DD208348A5/de not_active IP Right Cessation
1983
- 1983-01-17 ES ES519030A patent/ES519030A0/es active Granted
- 1983-01-17 ES ES519031A patent/ES519031A0/es active Granted
- 1983-01-17 ES ES519029A patent/ES8406413A1/es not_active Expired
- 1983-01-17 ES ES519032A patent/ES519032A0/es active Granted
1985
- 1985-01-09 SU SU853834158A patent/SU1461372A3/ru active
- 1985-01-17 YU YU63/85A patent/YU44253B/xx unknown
1987
- 1987-08-19 SG SG67287A patent/SG67287G/en unknown
- 1987-08-20 KE KE3753A patent/KE3753A/xx unknown
1988
- 1988-02-15 HK HK138/88A patent/HK13888A/xx not_active IP Right Cessation
- 1988-12-30 MY MY48/88A patent/MY8800048A/xx unknown
1994
- 1994-09-07 GE GEAP19942156A patent/GEP19970661B/en unknown

Also Published As

Publication number	Publication date
FR2504920A1 (fr)	1982-11-05
ES8406414A1 (es)	1984-08-01
LU84070A1 (fr)	1983-06-07
IL65257A0 (en)	1983-12-30
CS244672B2 (en)	1986-08-14
DK146482A (da)	1982-10-07
NL8201347A (nl)	1982-11-01
SG67287G (en)	1988-02-19
DK161770C (da)	1992-02-10
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NO156785C (no)	1987-11-25
BG40652A3 (en)	1986-01-15
PL240079A1 (en)	1983-09-12
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RO84802A (ro)	1984-09-29
KR830010065A (ko)	1983-12-26
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RO89436A2 (ro)	1986-06-30
YU75082A (en)	1985-08-31
PT74580B (en)	1983-12-23
RO84802B (ro)	1984-10-30
CH652117A5 (fr)	1985-10-31
HK13888A (en)	1988-02-26
NO156785B (no)	1987-08-17
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CY1408A (en)	1988-04-22
CA1248955A (en)	1989-01-17
ES8403097A1 (es)	1984-03-01
UA7838A1 (uk)	1995-12-26
DE3212682C2 (uk)	1992-03-26
SE8202166L (sv)	1982-11-25
ES519030A0 (es)	1984-08-01
PL235832A1 (en)	1983-09-12
GEP19970661B (en)	1997-01-04
DK161770B (da)	1991-08-12
BG40651A3 (en)	1986-01-15
GR76697B (uk)	1984-08-28
IN155773B (uk)	1985-03-09
DE3212682A1 (de)	1982-10-21
ES8407002A1 (es)	1984-08-16
GB2098602B (en)	1984-08-22
NO821087L (no)	1982-10-07
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UA7589A1 (uk)	1995-09-29
KR900000274B1 (ko)	1990-01-24
ATA132582A (de)	1986-08-15
FI821197A0 (fi)	1982-04-05
JO1184B1 (en)	1983-11-30
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PT74580A (en)	1982-04-01
IE52768B1 (en)	1988-02-17
SE452611B (sv)	1987-12-07
PH22762A (en)	1988-12-12
KE3753A (en)	1987-10-02
FR2504920B1 (fr)	1985-06-28
AU8221382A (en)	1982-10-14
NL192201B (nl)	1996-11-01
GB2098602A (en)	1982-11-24
SU1482522A3 (ru)	1989-05-23
IT8248157A0 (it)	1982-04-02
IT1235758B (it)	1992-09-28
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FI821197L (fi)	1982-10-07
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