GB1566761A - Benzylpyrrolidines process for their preparation and pharmaceutical compositions containing them - Google Patents
Benzylpyrrolidines process for their preparation and pharmaceutical compositions containing them Download PDFInfo
- Publication number
- GB1566761A GB1566761A GB31267/77A GB3126777A GB1566761A GB 1566761 A GB1566761 A GB 1566761A GB 31267/77 A GB31267/77 A GB 31267/77A GB 3126777 A GB3126777 A GB 3126777A GB 1566761 A GB1566761 A GB 1566761A
- Authority
- GB
- United Kingdom
- Prior art keywords
- group
- methylpyrrolidine
- addition salts
- acid addition
- radical
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired
Links
- 238000000034 method Methods 0.000 title claims description 60
- 230000008569 process Effects 0.000 title claims description 25
- 238000002360 preparation method Methods 0.000 title claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 4
- CWEGCQIIDCZZED-UHFFFAOYSA-N 1-benzylpyrrolidine Chemical class C=1C=CC=CC=1CN1CCCC1 CWEGCQIIDCZZED-UHFFFAOYSA-N 0.000 title description 5
- -1 alicyclic hydrocarbon radical Chemical class 0.000 claims description 125
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical class CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 claims description 75
- 150000001875 compounds Chemical class 0.000 claims description 65
- 150000003839 salts Chemical class 0.000 claims description 62
- 239000002253 acid Substances 0.000 claims description 57
- 125000004432 carbon atom Chemical group C* 0.000 claims description 56
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 41
- NKHMSOXIXROFRU-UHFFFAOYSA-N 2-benzylpyrrolidine Chemical class C=1C=CC=CC=1CC1CCCN1 NKHMSOXIXROFRU-UHFFFAOYSA-N 0.000 claims description 35
- 239000002585 base Substances 0.000 claims description 26
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 22
- 125000003277 amino group Chemical group 0.000 claims description 21
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 21
- 125000005843 halogen group Chemical group 0.000 claims description 20
- 125000003545 alkoxy group Chemical group 0.000 claims description 19
- 229930195733 hydrocarbon Natural products 0.000 claims description 18
- IQGVUZCAENHORR-UHFFFAOYSA-N 2-[(4-chlorophenyl)methyl]pyrrolidine Chemical compound C1=CC(Cl)=CC=C1CC1NCCC1 IQGVUZCAENHORR-UHFFFAOYSA-N 0.000 claims description 17
- 229910052740 iodine Inorganic materials 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 125000001424 substituent group Chemical group 0.000 claims description 17
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 239000004215 Carbon black (E152) Substances 0.000 claims description 13
- 125000004423 acyloxy group Chemical group 0.000 claims description 13
- 125000001931 aliphatic group Chemical group 0.000 claims description 12
- 239000007788 liquid Substances 0.000 claims description 11
- 230000036772 blood pressure Effects 0.000 claims description 10
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 10
- 239000012458 free base Substances 0.000 claims description 9
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
- 230000036407 pain Effects 0.000 claims description 9
- 238000011282 treatment Methods 0.000 claims description 9
- VDSNKERDALCECS-UHFFFAOYSA-N 4-[(1-methylpyrrolidin-2-yl)methyl]aniline Chemical compound CN1CCCC1CC1=CC=C(N)C=C1 VDSNKERDALCECS-UHFFFAOYSA-N 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- JNKCIXCNBFFNHD-UHFFFAOYSA-N 2-[(4-chlorophenyl)methyl]-1-methylpyrrolidine Chemical compound CN1CCCC1CC1=CC=C(Cl)C=C1 JNKCIXCNBFFNHD-UHFFFAOYSA-N 0.000 claims description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
- 125000006196 aroyl alkyl group Chemical group 0.000 claims description 7
- 210000003169 central nervous system Anatomy 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 239000007787 solid Substances 0.000 claims description 6
- YGWNSMNBSSEOTC-UHFFFAOYSA-N 2-[(2-chlorophenyl)methyl]-1-methylpyrrolidine Chemical compound CN1CCCC1CC1=CC=CC=C1Cl YGWNSMNBSSEOTC-UHFFFAOYSA-N 0.000 claims description 5
- YKTRGSOHLRFGAD-UHFFFAOYSA-N 2-[(3-methoxyphenyl)methyl]-1-methylpyrrolidine Chemical compound COC1=CC=CC(CC2N(CCC2)C)=C1 YKTRGSOHLRFGAD-UHFFFAOYSA-N 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 5
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- JIOKETBRNHZBHM-UHFFFAOYSA-N 2-[(2-methoxyphenyl)methyl]-1-methylpyrrolidine Chemical compound COC1=CC=CC=C1CC1N(C)CCC1 JIOKETBRNHZBHM-UHFFFAOYSA-N 0.000 claims description 4
- 150000003254 radicals Chemical class 0.000 claims description 4
- AYCAOTJKOPNLPV-UHFFFAOYSA-N 2-[(3-chlorophenyl)methyl]-1-methylpyrrolidine Chemical compound CN1CCCC1CC1=CC=CC(Cl)=C1 AYCAOTJKOPNLPV-UHFFFAOYSA-N 0.000 claims description 3
- YUOONPHJWMUTKO-UHFFFAOYSA-N 3-[(1-methylpyrrolidin-2-yl)methyl]phenol Chemical compound CN1CCCC1CC1=CC=CC(O)=C1 YUOONPHJWMUTKO-UHFFFAOYSA-N 0.000 claims description 3
- 241000124008 Mammalia Species 0.000 claims description 3
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical class [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 claims description 2
- 125000000524 functional group Chemical group 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 231100000915 pathological change Toxicity 0.000 claims description 2
- 230000036285 pathological change Effects 0.000 claims description 2
- 125000003884 phenylalkyl group Chemical class 0.000 claims description 2
- 239000002243 precursor Substances 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims 2
- YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical compound [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 125000002723 alicyclic group Chemical group 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 241
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 227
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 117
- 239000000243 solution Substances 0.000 description 111
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 85
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 84
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 81
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 75
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 57
- 238000006243 chemical reaction Methods 0.000 description 53
- 239000002904 solvent Substances 0.000 description 53
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 52
- 239000000203 mixture Substances 0.000 description 50
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- 239000003921 oil Substances 0.000 description 45
- 235000019198 oils Nutrition 0.000 description 45
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 44
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 40
- 238000010992 reflux Methods 0.000 description 36
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 35
- 238000003756 stirring Methods 0.000 description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
- 239000003054 catalyst Substances 0.000 description 29
- 238000001035 drying Methods 0.000 description 28
- 239000001257 hydrogen Substances 0.000 description 27
- 229910052739 hydrogen Inorganic materials 0.000 description 27
- 229910052938 sodium sulfate Inorganic materials 0.000 description 26
- 235000011152 sodium sulphate Nutrition 0.000 description 26
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 25
- 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 22
- 239000013543 active substance Substances 0.000 description 22
- 238000001816 cooling Methods 0.000 description 22
- 239000011734 sodium Substances 0.000 description 22
- 229910052708 sodium Inorganic materials 0.000 description 22
- 235000015424 sodium Nutrition 0.000 description 22
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 238000009835 boiling Methods 0.000 description 21
- 239000003814 drug Substances 0.000 description 21
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 20
- 238000000605 extraction Methods 0.000 description 20
- 239000000155 melt Substances 0.000 description 19
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 239000012071 phase Substances 0.000 description 18
- 229940075930 picrate Drugs 0.000 description 18
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 18
- 230000000694 effects Effects 0.000 description 17
- 229910052697 platinum Inorganic materials 0.000 description 17
- 239000007858 starting material Substances 0.000 description 17
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 16
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- 229960000583 acetic acid Drugs 0.000 description 16
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 15
- 238000001914 filtration Methods 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 13
- 239000013078 crystal Substances 0.000 description 13
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 13
- 229910052757 nitrogen Inorganic materials 0.000 description 13
- 230000009467 reduction Effects 0.000 description 13
- 238000006722 reduction reaction Methods 0.000 description 13
- 239000000706 filtrate Substances 0.000 description 12
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 10
- 238000004821 distillation Methods 0.000 description 10
- 239000005457 ice water Substances 0.000 description 10
- 239000012442 inert solvent Substances 0.000 description 10
- 239000012074 organic phase Substances 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 8
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 8
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
- 241000282414 Homo sapiens Species 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- 239000007868 Raney catalyst Substances 0.000 description 8
- 229910000564 Raney nickel Inorganic materials 0.000 description 8
- 230000000202 analgesic effect Effects 0.000 description 8
- 125000004093 cyano group Chemical group *C#N 0.000 description 8
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 8
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 8
- 230000007062 hydrolysis Effects 0.000 description 8
- 238000006460 hydrolysis reaction Methods 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 239000000546 pharmaceutical excipient Substances 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 150000003235 pyrrolidines Chemical class 0.000 description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 7
- 238000006114 decarboxylation reaction Methods 0.000 description 7
- 239000012280 lithium aluminium hydride Substances 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
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- 238000012360 testing method Methods 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- IVYMIRMKXZAHRV-UHFFFAOYSA-N 4-chlorophenylacetonitrile Chemical compound ClC1=CC=C(CC#N)C=C1 IVYMIRMKXZAHRV-UHFFFAOYSA-N 0.000 description 6
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 6
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- 150000001298 alcohols Chemical class 0.000 description 6
- 229910052783 alkali metal Inorganic materials 0.000 description 6
- 150000001340 alkali metals Chemical class 0.000 description 6
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
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- 235000012222 talc Nutrition 0.000 description 6
- 229910052623 talc Inorganic materials 0.000 description 6
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 6
- WIVVTFJOLNYKCP-UHFFFAOYSA-M 1-methyl-3,4-dihydro-2H-pyrrol-1-ium methyl sulfate Chemical compound COS(=O)(=O)[O-].C[N+]1=CCCC1 WIVVTFJOLNYKCP-UHFFFAOYSA-M 0.000 description 5
- RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical class C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 5
- 206010015995 Eyelid ptosis Diseases 0.000 description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 5
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 5
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- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 230000006399 behavior Effects 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 239000001569 carbon dioxide Substances 0.000 description 5
- 229910002092 carbon dioxide Inorganic materials 0.000 description 5
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 5
- AJELQWSOLJFIEQ-UHFFFAOYSA-M dimethyl-(1-methylpyrrolidin-2-ylidene)azanium;methyl sulfate Chemical compound COS([O-])(=O)=O.CN(C)C1=[N+](C)CCC1 AJELQWSOLJFIEQ-UHFFFAOYSA-M 0.000 description 5
- 239000012259 ether extract Substances 0.000 description 5
- 235000003599 food sweetener Nutrition 0.000 description 5
- HNJBEVLQSNELDL-UHFFFAOYSA-N gamma-butyrolactam Natural products O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 5
- 239000012362 glacial acetic acid Substances 0.000 description 5
- 150000002430 hydrocarbons Chemical class 0.000 description 5
- 229910017604 nitric acid Inorganic materials 0.000 description 5
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 201000003004 ptosis Diseases 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 5
- 239000001117 sulphuric acid Substances 0.000 description 5
- 235000011149 sulphuric acid Nutrition 0.000 description 5
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- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
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- 238000007911 parenteral administration Methods 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical compound OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 description 1
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- 125000004344 phenylpropyl group Chemical group 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
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- 229910052698 phosphorus Inorganic materials 0.000 description 1
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- 239000011591 potassium Substances 0.000 description 1
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- 238000001556 precipitation Methods 0.000 description 1
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- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
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- 238000011321 prophylaxis Methods 0.000 description 1
- LZFIOSVZIQOVFW-UHFFFAOYSA-N propyl 2-hydroxybenzoate Chemical class CCCOC(=O)C1=CC=CC=C1O LZFIOSVZIQOVFW-UHFFFAOYSA-N 0.000 description 1
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- 239000000376 reactant Substances 0.000 description 1
- MOODSJOROWROTO-UHFFFAOYSA-N salicylsulfuric acid Chemical compound OC(=O)C1=CC=CC=C1OS(O)(=O)=O MOODSJOROWROTO-UHFFFAOYSA-N 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- 239000005720 sucrose Substances 0.000 description 1
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- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
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- 229940095064 tartrate Drugs 0.000 description 1
- FUHZCTDEMXANRX-UHFFFAOYSA-N tert-butyl 2-(3,4-dimethoxyphenyl)acetate Chemical compound COC1=CC=C(CC(=O)OC(C)(C)C)C=C1OC FUHZCTDEMXANRX-UHFFFAOYSA-N 0.000 description 1
- KKJICVSBNBNCFX-UHFFFAOYSA-N tert-butyl 2-bromo-2-(4-methoxyphenyl)acetate Chemical compound COC1=CC=C(C(Br)C(=O)OC(C)(C)C)C=C1 KKJICVSBNBNCFX-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 235000015961 tonic Nutrition 0.000 description 1
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- 125000005490 tosylate group Chemical group 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
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- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 1
- CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- SCXZATZIVUFOFT-UHFFFAOYSA-N undec-5-ene Chemical compound [CH2]CCCC=CCCCCC SCXZATZIVUFOFT-UHFFFAOYSA-N 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
- 235000014692 zinc oxide Nutrition 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- 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
- C07D207/10—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 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
- C07D207/14—Nitrogen atoms not forming part of a nitro radical
-
- 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
- C07D207/18—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 one double bond between ring members or between a ring member and a non-ring member
- C07D207/20—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 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
- 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
- C07D207/18—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 one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—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 one double bond between ring members or between a ring member and a non-ring member 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
-
- 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
- C07D207/18—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 one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—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 one double bond between ring members or between a ring member and a non-ring member 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
- C07D207/24—Oxygen or sulfur atoms
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
LU75478A LU75478A1 (en, 2012) | 1976-07-28 | 1976-07-28 |
Publications (1)
Publication Number | Publication Date |
---|---|
GB1566761A true GB1566761A (en) | 1980-05-08 |
Family
ID=19728311
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB31267/77A Expired GB1566761A (en) | 1976-07-28 | 1977-07-26 | Benzylpyrrolidines process for their preparation and pharmaceutical compositions containing them |
Country Status (23)
Country | Link |
---|---|
US (1) | US4279918A (en, 2012) |
JP (1) | JPS5315367A (en, 2012) |
AT (1) | AT373580B (en, 2012) |
AU (1) | AU509015B2 (en, 2012) |
BE (1) | BE857289A (en, 2012) |
CA (1) | CA1104572A (en, 2012) |
CH (1) | CH639368A5 (en, 2012) |
DE (2) | DE2733817A1 (en, 2012) |
DK (1) | DK339677A (en, 2012) |
ES (1) | ES461077A1 (en, 2012) |
FR (1) | FR2359823A1 (en, 2012) |
GB (1) | GB1566761A (en, 2012) |
GR (1) | GR61367B (en, 2012) |
IE (1) | IE45320B1 (en, 2012) |
IL (1) | IL52611A (en, 2012) |
IT (1) | IT1085949B (en, 2012) |
LU (1) | LU75478A1 (en, 2012) |
NL (1) | NL7708306A (en, 2012) |
NZ (1) | NZ184755A (en, 2012) |
PT (1) | PT66858B (en, 2012) |
SE (1) | SE429338B (en, 2012) |
YU (1) | YU184277A (en, 2012) |
ZA (1) | ZA774553B (en, 2012) |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU518986B2 (en) * | 1977-10-11 | 1981-10-29 | Takeda Chemical Industries Ltd. | Lactams |
DE2952382A1 (de) * | 1979-12-24 | 1981-07-16 | Basf Ag, 6700 Ludwigshafen | Phenylpropylammoniumsalze, verfahren zu ihrer herstellung und diese verbindungen enthaltende mittel |
US4826869A (en) * | 1988-02-19 | 1989-05-02 | Syntex (U.S.A.) Inc. | N-(lower alkyl)-2-(3'ureidobenzyl)pyrrolidines |
US5100912A (en) * | 1990-05-14 | 1992-03-31 | Syntex (U.S.A.) Inc. | Bis(benzylpyrrolidine) derivatives as dopamine agonists |
US5135944A (en) * | 1989-06-21 | 1992-08-04 | Syntex (U.S.A.) Inc. | Bis(benzylpyrrolidine) derivatives useful for treating congestive heart failure and acute renal failure |
HUT58050A (en) * | 1989-06-21 | 1992-01-28 | Syntex Inc | Process for producing 2-(3,4-dialkoxybenzyl)-pyrrolidines |
US5093355A (en) * | 1989-10-30 | 1992-03-03 | Syntex (U.S.A.) Inc. | Benzylpyrrolidine derivatives as dopamine agonists |
US5130432A (en) * | 1990-12-21 | 1992-07-14 | Syntex (U.S.A.) Inc. | Process for preparing cyclic amines and intermediate products thereof |
EP0562185A1 (en) * | 1992-03-17 | 1993-09-29 | Council of Scientific and Industrial Research | 3-(Arylmethyl)-1-(3'-diethylaminopropyl) pyrrolidines and process of preparation thereof |
US5248690A (en) * | 1992-07-07 | 1993-09-28 | R. J. Reynolds Tobacco Company | Method for treatment of neurodegenerative diseases |
US7208517B1 (en) * | 1994-08-19 | 2007-04-24 | Abbott Labortories | Endothelin antagonists |
CN104292143A (zh) * | 2014-08-17 | 2015-01-21 | 湖南华腾制药有限公司 | 一种2-(4-溴苄基)吡咯烷的制备方法 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE1049380B (de) * | 1959-01-29 | Bergisch Gladbach Adolf Christian Josef Opfermann | Verfahren zur Herstellung von a-substituierten Pyrrolidinen | |
FR86099E (fr) | 1963-08-20 | 1965-12-03 | Pechiney Saint Gobain | Dérivés de la delta1-pyrroline |
DE1470387A1 (de) | 1963-12-20 | 1969-05-29 | Union Carbide Corp | Verfahren zur Herstellung von substituierten Pyrrolderivaten |
GB1168797A (en) | 1965-12-09 | 1969-10-29 | Nat Res Dev | Cyclopropane Carboxylic Acid Derivatives and their use as Insecticides |
US3647790A (en) * | 1969-04-08 | 1972-03-07 | American Home Prod | Ouinoxalinyl-oxazolidines and -oxazines |
-
1976
- 1976-07-28 LU LU75478A patent/LU75478A1/xx unknown
-
1977
- 1977-07-26 GB GB31267/77A patent/GB1566761A/en not_active Expired
- 1977-07-26 YU YU01842/77A patent/YU184277A/xx unknown
- 1977-07-27 NZ NZ184755A patent/NZ184755A/xx unknown
- 1977-07-27 FR FR7723030A patent/FR2359823A1/fr active Granted
- 1977-07-27 CA CA283,611A patent/CA1104572A/en not_active Expired
- 1977-07-27 ZA ZA00774553A patent/ZA774553B/xx unknown
- 1977-07-27 IT IT26204/77A patent/IT1085949B/it active
- 1977-07-27 DE DE19772733817 patent/DE2733817A1/de not_active Ceased
- 1977-07-27 JP JP8939377A patent/JPS5315367A/ja active Pending
- 1977-07-27 DE DE19772733753 patent/DE2733753A1/de not_active Withdrawn
- 1977-07-27 NL NL7708306A patent/NL7708306A/xx not_active Application Discontinuation
- 1977-07-27 PT PT66858A patent/PT66858B/pt unknown
- 1977-07-27 DK DK339677A patent/DK339677A/da not_active Application Discontinuation
- 1977-07-27 CH CH929477A patent/CH639368A5/de not_active IP Right Cessation
- 1977-07-27 IL IL52611A patent/IL52611A/xx unknown
- 1977-07-27 SE SE7708621A patent/SE429338B/xx unknown
- 1977-07-27 GR GR54055A patent/GR61367B/el unknown
- 1977-07-27 AT AT0548177A patent/AT373580B/de active
- 1977-07-27 US US05/819,460 patent/US4279918A/en not_active Expired - Lifetime
- 1977-07-27 IE IE1567/77A patent/IE45320B1/en unknown
- 1977-07-27 ES ES461077A patent/ES461077A1/es not_active Expired
- 1977-07-27 AU AU27365/77A patent/AU509015B2/en not_active Expired
- 1977-07-28 BE BE6046095A patent/BE857289A/xx not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
IL52611A0 (en) | 1977-10-31 |
DK339677A (da) | 1978-01-29 |
GR61367B (en) | 1978-10-30 |
FR2359823B1 (en, 2012) | 1980-11-21 |
CA1104572A (en) | 1981-07-07 |
IL52611A (en) | 1981-10-30 |
ZA774553B (en) | 1978-06-28 |
AT373580B (de) | 1984-02-10 |
NZ184755A (en) | 1979-12-11 |
YU184277A (en) | 1983-02-28 |
FR2359823A1 (fr) | 1978-02-24 |
NL7708306A (nl) | 1978-01-31 |
PT66858B (de) | 1979-03-13 |
JPS5315367A (en) | 1978-02-13 |
IT1085949B (it) | 1985-05-28 |
US4279918A (en) | 1981-07-21 |
AU509015B2 (en) | 1980-04-17 |
BE857289A (fr) | 1978-01-30 |
LU75478A1 (en, 2012) | 1978-02-08 |
IE45320B1 (en) | 1982-07-28 |
DE2733817A1 (de) | 1978-02-02 |
SE7708621L (sv) | 1978-01-29 |
IE45320L (en) | 1978-01-28 |
CH639368A5 (de) | 1983-11-15 |
PT66858A (de) | 1977-08-01 |
SE429338B (sv) | 1983-08-29 |
AU2736577A (en) | 1979-02-01 |
ATA548177A (de) | 1983-06-15 |
ES461077A1 (es) | 1978-12-01 |
DE2733753A1 (de) | 1978-02-02 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
PS | Patent sealed [section 19, patents act 1949] | ||
PCNP | Patent ceased through non-payment of renewal fee |