DK171349B1 - Tetrahydronaphthalenderivater, fremgangsmåde til fremstilling deraf, lægemidler indeholdende forbindelserne samt anvendelse af forbindelserne til fremstilling af lægemidler - Google Patents

Tetrahydronaphthalenderivater, fremgangsmåde til fremstilling deraf, lægemidler indeholdende forbindelserne samt anvendelse af forbindelserne til fremstilling af lægemidler Download PDF

Info

Publication number: DK171349B1
Authority: DK; Denmark
Prior art keywords: tetrahydro; isopropyl; ethyl; methylamino; benzimidazolyl
Prior art date: 1986-11-14

Application number

DK559987A

Other languages

Danish (da)

English (en)

Other versions

DK559987D0 (da

DK559987A (da

Inventor

Quirico Branca

Roland Jaunin

Hans Peter Maerki

Fraenzi Marti

Henri Ramuz

Original Assignee

Hoffmann La Roche

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.)

1986-11-14

Filing date

1987-10-26

Publication date

1996-09-16

1987-10-26 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1987-10-26 Publication of DK559987D0 publication Critical patent/DK559987D0/da

1988-05-15 Publication of DK559987A publication Critical patent/DK559987A/da

1996-09-16 Application granted granted Critical

1996-09-16 Publication of DK171349B1 publication Critical patent/DK171349B1/da

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 79
239000003814 drug Substances 0.000 title claims abstract description 8
238000000034 method Methods 0.000 title claims description 14
238000002360 preparation method Methods 0.000 title claims description 14
238000004519 manufacturing process Methods 0.000 title description 3
-1 tri-substituted 2-imidazolyl Chemical group 0.000 claims abstract description 126
150000003839 salts Chemical class 0.000 claims abstract description 18
239000002253 acid Substances 0.000 claims abstract description 17
125000005195 alkyl amino carbonyloxy group Chemical group 0.000 claims abstract description 11
150000001204 N-oxides Chemical class 0.000 claims abstract description 9
206010002383 Angina Pectoris Diseases 0.000 claims abstract description 8
230000003287 optical effect Effects 0.000 claims abstract description 8
206010019280 Heart failures Diseases 0.000 claims abstract description 7
206010020772 Hypertension Diseases 0.000 claims abstract description 7
206010003119 arrhythmia Diseases 0.000 claims abstract description 7
230000006793 arrhythmia Effects 0.000 claims abstract description 7
229910052736 halogen Inorganic materials 0.000 claims abstract description 7
208000028867 ischemia Diseases 0.000 claims abstract description 7
230000002265 prevention Effects 0.000 claims abstract description 4
125000004955 1,4-cyclohexylene group Chemical group [H]C1([H])C([H])([H])C([H])([*:1])C([H])([H])C([H])([H])C1([H])[*:2] 0.000 claims abstract description 3
125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims abstract description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 54
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 46
125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 26
125000000217 alkyl group Chemical group 0.000 claims description 16
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 15
125000003545 alkoxy group Chemical group 0.000 claims description 12
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 11
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
125000003118 aryl group Chemical group 0.000 claims description 9
150000002367 halogens Chemical class 0.000 claims description 6
LKFQQNHKZPKYLK-URLMMPGGSA-N C1=CC=C2NC(CCCN(C)CC[C@]3(CCC4=CC(F)=CC=C4[C@@H]3C(C)C)COCC(O)=O)=NC2=C1 Chemical compound C1=CC=C2NC(CCCN(C)CC[C@]3(CCC4=CC(F)=CC=C4[C@@H]3C(C)C)COCC(O)=O)=NC2=C1 LKFQQNHKZPKYLK-URLMMPGGSA-N 0.000 claims description 5
239000003795 chemical substances by application Substances 0.000 claims description 5
239000000546 pharmaceutical excipient Substances 0.000 claims description 5
239000013543 active substance Substances 0.000 claims description 4
150000001412 amines Chemical class 0.000 claims description 4
229910052731 fluorine Inorganic materials 0.000 claims description 4
239000011737 fluorine Substances 0.000 claims description 4
125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 3
125000002947 alkylene group Chemical group 0.000 claims description 3
239000012948 isocyanate Substances 0.000 claims description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
FTBKIEKALBEBRE-UHFFFAOYSA-N 2-[(1-propan-2-yl-1,2,3,4-tetrahydronaphthalen-2-yl)methoxy]acetic acid Chemical compound CC(C)C1C(CCC2=CC=CC=C12)COCC(=O)O FTBKIEKALBEBRE-UHFFFAOYSA-N 0.000 claims description 2
125000001153 fluoro group Chemical group F* 0.000 claims description 2
CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical class C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 claims description 2
230000001225 therapeutic effect Effects 0.000 claims description 2
125000004076 pyridyl group Chemical group 0.000 claims 1
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 abstract description 5
125000005843 halogen group Chemical group 0.000 abstract description 3
230000002213 calciumantagonistic effect Effects 0.000 abstract description 2
125000000623 heterocyclic group Chemical group 0.000 abstract description 2
125000004400 (C1-C12) alkyl group Chemical group 0.000 abstract 1
230000003288 anthiarrhythmic effect Effects 0.000 abstract 1
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 abstract 1
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 240
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 222
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 111
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 96
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 60
239000000203 mixture Substances 0.000 description 59
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 58
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 58
239000000243 solution Substances 0.000 description 55
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
239000003921 oil Substances 0.000 description 53
235000019198 oils Nutrition 0.000 description 53
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 46
239000011541 reaction mixture Substances 0.000 description 44
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 41
239000000741 silica gel Substances 0.000 description 41
229910002027 silica gel Inorganic materials 0.000 description 41
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 40
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
238000006243 chemical reaction Methods 0.000 description 33
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 30
235000002639 sodium chloride Nutrition 0.000 description 26
239000000284 extract Substances 0.000 description 25
239000007858 starting material Substances 0.000 description 24
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 23
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 23
239000002904 solvent Substances 0.000 description 21
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
239000003480 eluent Substances 0.000 description 20
229910052943 magnesium sulfate Inorganic materials 0.000 description 20
235000019341 magnesium sulphate Nutrition 0.000 description 20
238000003756 stirring Methods 0.000 description 20
239000012074 organic phase Substances 0.000 description 19
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
239000000843 powder Substances 0.000 description 18
229920006395 saturated elastomer Polymers 0.000 description 18
239000005457 ice water Substances 0.000 description 17
238000010992 reflux Methods 0.000 description 17
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
VRZVPALEJCLXPR-UHFFFAOYSA-N ethyl 4-methylbenzenesulfonate Chemical compound CCOS(=O)(=O)C1=CC=C(C)C=C1 VRZVPALEJCLXPR-UHFFFAOYSA-N 0.000 description 16
238000001704 evaporation Methods 0.000 description 16
229910052799 carbon Inorganic materials 0.000 description 15
230000008020 evaporation Effects 0.000 description 15
229910000027 potassium carbonate Inorganic materials 0.000 description 15
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 14
PEHFQQWAINXOQG-UHFFFAOYSA-N (2-methoxyacetyl) 2-methoxyacetate Chemical compound COCC(=O)OC(=O)COC PEHFQQWAINXOQG-UHFFFAOYSA-N 0.000 description 12
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 12
239000012043 crude product Substances 0.000 description 12
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 11
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 11
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 11
239000011780 sodium chloride Substances 0.000 description 11
239000012312 sodium hydride Substances 0.000 description 11
229910000104 sodium hydride Inorganic materials 0.000 description 11
238000001816 cooling Methods 0.000 description 10
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
239000007864 aqueous solution Substances 0.000 description 9
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 9
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 9
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
229910052938 sodium sulfate Inorganic materials 0.000 description 9
235000011152 sodium sulphate Nutrition 0.000 description 9
239000000725 suspension Substances 0.000 description 9
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 8
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 8
239000008346 aqueous phase Substances 0.000 description 8
239000002775 capsule Substances 0.000 description 8
239000006185 dispersion Substances 0.000 description 8
238000001035 drying Methods 0.000 description 8
239000002480 mineral oil Substances 0.000 description 8
235000010446 mineral oil Nutrition 0.000 description 8
239000002244 precipitate Substances 0.000 description 8
235000017557 sodium bicarbonate Nutrition 0.000 description 8
229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
239000007787 solid Substances 0.000 description 8
239000000454 talc Substances 0.000 description 8
235000012222 talc Nutrition 0.000 description 8
229910052623 talc Inorganic materials 0.000 description 8
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 8
229920002261 Corn starch Polymers 0.000 description 7
239000008120 corn starch Substances 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
125000004356 hydroxy functional group Chemical group O* 0.000 description 7
235000019359 magnesium stearate Nutrition 0.000 description 7
GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 7
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
235000011114 ammonium hydroxide Nutrition 0.000 description 6
229950011260 betanaphthol Drugs 0.000 description 6
238000004587 chromatography analysis Methods 0.000 description 6
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
239000000047 product Substances 0.000 description 6
239000000126 substance Substances 0.000 description 6
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
230000017531 blood circulation Effects 0.000 description 5
239000013078 crystal Substances 0.000 description 5
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
229910000041 hydrogen chloride Inorganic materials 0.000 description 5
238000005259 measurement Methods 0.000 description 5
229910052763 palladium Inorganic materials 0.000 description 5
238000001665 trituration Methods 0.000 description 5
230000002861 ventricular Effects 0.000 description 5
YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 4
RAWYKGLVQSJJPW-UHFFFAOYSA-N 3-[4-(methylamino)butyl]-1h-benzimidazol-2-one Chemical compound C1=CC=C2NC(=O)N(CCCCNC)C2=C1 RAWYKGLVQSJJPW-UHFFFAOYSA-N 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
229920002472 Starch Polymers 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
239000000908 ammonium hydroxide Substances 0.000 description 4
229910052786 argon Inorganic materials 0.000 description 4
230000036772 blood pressure Effects 0.000 description 4
210000004351 coronary vessel Anatomy 0.000 description 4
230000000694 effects Effects 0.000 description 4
238000001914 filtration Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
238000002347 injection Methods 0.000 description 4
229920005862 polyol Polymers 0.000 description 4
150000003077 polyols Chemical class 0.000 description 4
239000011734 sodium Substances 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
239000008107 starch Substances 0.000 description 4
235000019698 starch Nutrition 0.000 description 4
GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
LXYOUUGAHXHMDC-UHFFFAOYSA-N 1-[4-(1h-benzimidazol-2-ylmethyl)phenyl]-n-methylmethanamine Chemical compound C1=CC(CNC)=CC=C1CC1=NC2=CC=CC=C2N1 LXYOUUGAHXHMDC-UHFFFAOYSA-N 0.000 description 3
SVEOOBQTMUDYJD-UHFFFAOYSA-N 1-[4-(methylamino)butyl]-3-propan-2-ylbenzimidazol-2-one Chemical compound C1=CC=C2N(C(C)C)C(=O)N(CCCCNC)C2=C1 SVEOOBQTMUDYJD-UHFFFAOYSA-N 0.000 description 3
OYQNKVONRPMLEF-UHFFFAOYSA-N 1-methyl-3-[6-(methylamino)hexyl]benzimidazol-2-one Chemical compound C1=CC=C2N(C)C(=O)N(CCCCCCNC)C2=C1 OYQNKVONRPMLEF-UHFFFAOYSA-N 0.000 description 3
VMZCBGQDEWCDBV-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-n-methylpropan-1-amine Chemical compound C1=CC=C2NC(CCCNC)=NC2=C1 VMZCBGQDEWCDBV-UHFFFAOYSA-N 0.000 description 3
DLHYYRZDJVRJQW-UHFFFAOYSA-N 3-(4,5-diphenyl-1h-imidazol-2-yl)-n-methylpropan-1-amine Chemical compound N1C(CCCNC)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 DLHYYRZDJVRJQW-UHFFFAOYSA-N 0.000 description 3
JMZPSCHEKARHEP-UHFFFAOYSA-N 3-[2-(methylamino)ethyl]-1h-benzimidazol-2-one;hydrochloride Chemical compound Cl.C1=CC=C2NC(=O)N(CCNC)C2=C1 JMZPSCHEKARHEP-UHFFFAOYSA-N 0.000 description 3
UBAISFACDKAJPF-UHFFFAOYSA-N 4-(1h-benzimidazol-2-ylmethyl)benzonitrile Chemical compound C1=CC(C#N)=CC=C1CC1=NC2=CC=CC=C2N1 UBAISFACDKAJPF-UHFFFAOYSA-N 0.000 description 3
VCDKZPMRQQQCAZ-UHFFFAOYSA-N 4-[methyl(phenylmethoxycarbonyl)amino]butanoic acid Chemical compound OC(=O)CCCN(C)C(=O)OCC1=CC=CC=C1 VCDKZPMRQQQCAZ-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
HZTCKHKEWKTTHW-JOCQHMNTSA-N C1C[C@@H](CNC)CC[C@@H]1C1=NC2=CC=CC=C2N1C Chemical compound C1C[C@@H](CNC)CC[C@@H]1C1=NC2=CC=CC=C2N1C HZTCKHKEWKTTHW-JOCQHMNTSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
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150000004945 aromatic hydrocarbons Chemical class 0.000 description 3
HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
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 3
239000008298 dragée Substances 0.000 description 3
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150000002170 ethers Chemical class 0.000 description 3
239000007903 gelatin capsule Substances 0.000 description 3
239000008187 granular material Substances 0.000 description 3
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XUAURPJQDNPORU-UHFFFAOYSA-N n-methyl-1-[4-[(1-methylbenzimidazol-2-yl)methyl]phenyl]methanamine Chemical compound C1=CC(CNC)=CC=C1CC1=NC2=CC=CC=C2N1C XUAURPJQDNPORU-UHFFFAOYSA-N 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
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VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
230000001960 triggered effect Effects 0.000 description 1
JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229960001722 verapamil Drugs 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
- 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
- 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
- A61P9/06—Antiarrhythmics
- 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
- A61P9/08—Vasodilators for multiple indications
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- 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
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/14—Radicals substituted by nitrogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles 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 in position 2
- C07D235/26—Oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/64—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Vascular Medicine (AREA)
Urology & Nephrology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Luminescent Compositions (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Electrical Discharge Machining, Electrochemical Machining, And Combined Machining (AREA)
Organic Insulating Materials (AREA)
Hydrogenated Pyridines (AREA)
Steroid Compounds (AREA)
Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

DK559987A 1986-11-14 1987-10-26 Tetrahydronaphthalenderivater, fremgangsmåde til fremstilling deraf, lægemidler indeholdende forbindelserne samt anvendelse af forbindelserne til fremstilling af lægemidler DK171349B1 (da)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
CH456586		1986-11-14
CH456586		1986-11-14

Publications (3)

Publication Number	Publication Date
DK559987D0 DK559987D0 (da)	1987-10-26
DK559987A DK559987A (da)	1988-05-15
DK171349B1 true DK171349B1 (da)	1996-09-16

Family

ID=4278454

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DK559987A DK171349B1 (da)	1986-11-14	1987-10-26	Tetrahydronaphthalenderivater, fremgangsmåde til fremstilling deraf, lægemidler indeholdende forbindelserne samt anvendelse af forbindelserne til fremstilling af lægemidler

Country Status (31)

Country	Link
US (1)	US4808605A (cs)
EP (1)	EP0268148B1 (cs)
JP (1)	JP2504490B2 (cs)
KR (1)	KR960004863B1 (cs)
CN (1)	CN1028991C (cs)
AT (1)	ATE70267T1 (cs)
AU (1)	AU600769B2 (cs)
BG (1)	BG60937B2 (cs)
CA (1)	CA1319144C (cs)
CS (2)	CS264350B2 (cs)
DE (2)	DE3775177D1 (cs)
DK (1)	DK171349B1 (cs)
DZ (1)	DZ1142A1 (cs)
ES (1)	ES2040234T3 (cs)
FI (1)	FI94414C (cs)
GR (1)	GR3004029T3 (cs)
HK (1)	HK110494A (cs)
HU (1)	HU215915B (cs)
IE (1)	IE60695B1 (cs)
IL (1)	IL84407A (cs)
LV (1)	LV5745B4 (cs)
MC (1)	MC1883A1 (cs)
MX (1)	MX173614B (cs)
NL (1)	NL970019I2 (cs)
NO (2)	NO172237C (cs)
NZ (1)	NZ222474A (cs)
PH (1)	PH23919A (cs)
PT (1)	PT86130B (cs)
SG (1)	SG114194G (cs)
ZA (1)	ZA878362B (cs)
ZW (1)	ZW20087A1 (cs)

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EP1796653A2 (en) *	2004-07-26	2007-06-20	Actelion Pharmaceuticals Ltd.	Treatment of pulmonary hypertension by inhaled iloprost with a microparticle formulation
US7741317B2 (en)	2005-10-21	2010-06-22	Bristol-Myers Squibb Company	LXR modulators
US7893050B2 (en) *	2005-10-26	2011-02-22	Asahi Kasei Pharma Corporation	Fasudil in combination therapies for the treatment of pulmonary arterial hypertension
EP2351569B1 (en)	2005-10-26	2012-08-22	Asahi Kasei Pharma Corporation	Fasudil in combination therapies for the treatment of pulmonary arterial hypertension
US7888376B2 (en)	2005-11-23	2011-02-15	Bristol-Myers Squibb Company	Heterocyclic CETP inhibitors
US7919506B2 (en)	2006-03-10	2011-04-05	Pfizer Inc.	Dibenzyl amine compounds and derivatives
JP5498168B2 (ja)	2006-12-01	2014-05-21	ブリストル−マイヤーズスクイブカンパニー	アテローム性動脈硬化および循環器疾患の治療のためのｃｅｔｐ阻害剤としてのｎ−（（３−ベンジル）−２，２−（ビス−フェニル）−プロパン−１−アミン誘導体
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EP2995303A1 (en)	2009-07-10	2016-03-16	President and Fellows of Harvard College	Permanently charged sodium and calcium channel blockers as anti-inflammatory agents
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1987
- 1987-10-26 CA CA000550190A patent/CA1319144C/en not_active Expired - Fee Related
- 1987-10-26 DK DK559987A patent/DK171349B1/da not_active IP Right Cessation
- 1987-11-03 ZW ZW200/87A patent/ZW20087A1/xx unknown
- 1987-11-03 CS CS877874A patent/CS264350B2/cs not_active IP Right Cessation
- 1987-11-04 DE DE8787116251T patent/DE3775177D1/de not_active Expired - Lifetime
- 1987-11-04 ES ES198787116251T patent/ES2040234T3/es not_active Expired - Lifetime
- 1987-11-04 EP EP87116251A patent/EP0268148B1/de not_active Expired - Lifetime
- 1987-11-04 DE DE1997175076 patent/DE19775076I2/de active Active
- 1987-11-04 AT AT87116251T patent/ATE70267T1/de active
- 1987-11-06 NZ NZ222474A patent/NZ222474A/xx unknown
- 1987-11-06 ZA ZA878362A patent/ZA878362B/xx unknown
- 1987-11-09 AU AU80909/87A patent/AU600769B2/en not_active Ceased
- 1987-11-09 IL IL84407A patent/IL84407A/xx unknown
- 1987-11-10 JP JP62282287A patent/JP2504490B2/ja not_active Expired - Lifetime
- 1987-11-10 US US07/119,114 patent/US4808605A/en not_active Expired - Lifetime
- 1987-11-11 DZ DZ870191A patent/DZ1142A1/fr active
- 1987-11-11 PH PH36056A patent/PH23919A/en unknown
- 1987-11-11 HU HU875011A patent/HU215915B/hu not_active IP Right Cessation
- 1987-11-12 MC MC871928A patent/MC1883A1/fr unknown
- 1987-11-12 MX MX009271A patent/MX173614B/es unknown
- 1987-11-13 CN CN87107875A patent/CN1028991C/zh not_active Expired - Fee Related
- 1987-11-13 NO NO874757A patent/NO172237C/no not_active IP Right Cessation
- 1987-11-13 PT PT86130A patent/PT86130B/pt not_active IP Right Cessation
- 1987-11-13 KR KR87012777A patent/KR960004863B1/ko not_active Expired - Fee Related
- 1987-11-13 FI FI875024A patent/FI94414C/fi not_active IP Right Cessation
- 1987-11-13 IE IE307087A patent/IE60695B1/en not_active IP Right Cessation
1991
- 1991-12-20 CS CS913948A patent/CS394891A3/cs unknown
1992
- 1992-03-11 GR GR920400420T patent/GR3004029T3/el unknown
1994
- 1994-02-14 BG BG098469A patent/BG60937B2/bg unknown
- 1994-08-13 SG SG114194A patent/SG114194G/en unknown
- 1994-10-12 HK HK110494A patent/HK110494A/xx not_active IP Right Cessation
1996
- 1996-05-24 LV LV960155A patent/LV5745B4/xx unknown
1997
- 1997-05-27 NL NL970019C patent/NL970019I2/nl unknown
1998
- 1998-01-09 NO NO1998001C patent/NO1998001I1/no unknown

Also Published As

Publication number	Publication date
GR3004029T3 (cs)	1993-03-31
LV5745A4 (lv)	1996-10-20
JPS63139171A (ja)	1988-06-10
CS787487A2 (en)	1988-11-15
NO172237B (no)	1993-03-15
CS394891A3 (en)	1992-06-17
FI94414B (fi)	1995-05-31
JP2504490B2 (ja)	1996-06-05
FI94414C (fi)	1995-09-11
DK559987D0 (da)	1987-10-26
IE60695B1 (en)	1994-08-10
DZ1142A1 (fr)	2004-09-13
FI875024A0 (fi)	1987-11-13
BG60937B2 (bg)	1996-06-28
CA1319144C (en)	1993-06-15
MX173614B (es)	1994-03-18
PT86130B (pt)	1990-11-20
NL970019I2 (nl)	1997-11-03
PT86130A (en)	1987-12-01
CN1028991C (zh)	1995-06-21
HUT60251A (en)	1992-08-28
AU8090987A (en)	1988-05-19
FI875024A7 (fi)	1988-05-15
NZ222474A (en)	1990-02-26
DK559987A (da)	1988-05-15
IL84407A (en)	1991-09-16
EP0268148A1 (de)	1988-05-25
NO874757L (no)	1988-05-16
NL970019I1 (nl)	1997-08-01
MX9271A (es)	1993-09-01
LV5745B4 (lv)	1996-12-20
DE19775076I2 (de)	2001-08-09
IE873070L (en)	1988-05-14
KR880006163A (ko)	1988-07-21
SG114194G (en)	1994-11-25
CN87107875A (zh)	1988-05-25
CS264350B2 (en)	1989-07-12
HU215915B (hu)	1999-03-29
AU600769B2 (en)	1990-08-23
NO1998001I1 (no)	1998-01-09
NO874757D0 (no)	1987-11-13
HK110494A (en)	1994-10-21
ES2040234T3 (es)	1993-10-16
MC1883A1 (fr)	1989-01-24
IL84407A0 (en)	1988-04-29
US4808605A (en)	1989-02-28
PH23919A (en)	1990-01-23
EP0268148B1 (de)	1991-12-11
NO172237C (no)	1993-06-23
ZW20087A1 (en)	1988-07-20
ZA878362B (en)	1988-05-16
DE3775177D1 (de)	1992-01-23
KR960004863B1 (en)	1996-04-16
ATE70267T1 (de)	1991-12-15

Legal Events

Date	Code	Title	Description
1996-09-16	B1	Patent granted (law 1993)
1997-09-15	CTFF	Application for supplementary protection certificate (spc) filed	Free format text: CA 1997 00033, 970731
1998-05-25	CTFG	Supplementary protection certificate (spc) issued	Free format text: CA 1997 00033, 970731, EXPIRES: 20111220
2004-06-07	PBP	Patent lapsed	Country of ref document: DK

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