NZ246441A - Imidazol or imidazolalkyl substituted with a 4 or 5 membered nitrogen containing heterocycle, preparation and pharmaceutical compositions thereof - Google Patents
Imidazol or imidazolalkyl substituted with a 4 or 5 membered nitrogen containing heterocycle, preparation and pharmaceutical compositions thereofInfo
- Publication number
- NZ246441A NZ246441A NZ246441A NZ24644192A NZ246441A NZ 246441 A NZ246441 A NZ 246441A NZ 246441 A NZ246441 A NZ 246441A NZ 24644192 A NZ24644192 A NZ 24644192A NZ 246441 A NZ246441 A NZ 246441A
- Authority
- NZ
- New Zealand
- Prior art keywords
- compound
- pct
- group
- formula
- alkyl
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 9
- 238000002360 preparation method Methods 0.000 title description 83
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 322
- 238000000034 method Methods 0.000 claims abstract description 37
- 150000003839 salts Chemical class 0.000 claims abstract description 21
- 239000003937 drug carrier Substances 0.000 claims abstract description 5
- 239000012453 solvate Substances 0.000 claims abstract description 4
- 239000000203 mixture Substances 0.000 claims description 62
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 34
- 125000000217 alkyl group Chemical group 0.000 claims description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- 125000001424 substituent group Chemical group 0.000 claims description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
- 102000004384 Histamine H3 receptors Human genes 0.000 claims description 11
- 108090000981 Histamine H3 receptors Proteins 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 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 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 5
- 239000000556 agonist Substances 0.000 claims description 5
- 239000008187 granular material Substances 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 5
- 239000005557 antagonist Substances 0.000 claims description 4
- 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 claims description 3
- 235000013305 food Nutrition 0.000 claims description 3
- 239000008101 lactose Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 229920002472 Starch Polymers 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000004615 ingredient Substances 0.000 claims description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 2
- 235000019698 starch Nutrition 0.000 claims description 2
- 239000008107 starch Substances 0.000 claims description 2
- 239000007903 gelatin capsule Substances 0.000 claims 1
- 230000002378 acidificating effect Effects 0.000 abstract description 4
- 230000004410 intraocular pressure Effects 0.000 abstract description 4
- 206010020772 Hypertension Diseases 0.000 abstract description 3
- 206010061218 Inflammation Diseases 0.000 abstract description 3
- 208000019695 Migraine disease Diseases 0.000 abstract description 3
- 208000006673 asthma Diseases 0.000 abstract description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract description 3
- 230000004054 inflammatory process Effects 0.000 abstract description 3
- 206010027599 migraine Diseases 0.000 abstract description 3
- 230000028327 secretion Effects 0.000 abstract description 3
- 206010011953 Decreased activity Diseases 0.000 abstract description 2
- 208000010412 Glaucoma Diseases 0.000 abstract description 2
- 206010020751 Hypersensitivity Diseases 0.000 abstract description 2
- 238000013019 agitation Methods 0.000 abstract description 2
- 208000026935 allergic disease Diseases 0.000 abstract description 2
- 230000007815 allergy Effects 0.000 abstract description 2
- 210000003169 central nervous system Anatomy 0.000 abstract description 2
- 208000015114 central nervous system disease Diseases 0.000 abstract description 2
- 208000035475 disorder Diseases 0.000 abstract description 2
- 208000013403 hyperactivity Diseases 0.000 abstract description 2
- 230000004899 motility Effects 0.000 abstract description 2
- 201000000980 schizophrenia Diseases 0.000 abstract description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 141
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 92
- 239000000243 solution Substances 0.000 description 90
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 80
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 70
- 238000006243 chemical reaction Methods 0.000 description 65
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 55
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 45
- 239000003960 organic solvent Substances 0.000 description 44
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 43
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 38
- 239000002904 solvent Substances 0.000 description 36
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 34
- 235000019439 ethyl acetate Nutrition 0.000 description 31
- 239000007787 solid Substances 0.000 description 31
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 29
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 25
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 24
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 21
- 239000002585 base Substances 0.000 description 18
- 238000003818 flash chromatography Methods 0.000 description 17
- 150000007530 organic bases Chemical class 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 229910001868 water Inorganic materials 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- 229920006395 saturated elastomer Polymers 0.000 description 15
- 239000012043 crude product Substances 0.000 description 14
- 239000012044 organic layer Substances 0.000 description 14
- 239000012267 brine Substances 0.000 description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 239000010410 layer Substances 0.000 description 12
- 125000006239 protecting group Chemical group 0.000 description 12
- 229940086542 triethylamine Drugs 0.000 description 12
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical class NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 11
- 229910007161 Si(CH3)3 Inorganic materials 0.000 description 11
- -1 piperonyi Chemical group 0.000 description 11
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- 235000019441 ethanol Nutrition 0.000 description 10
- 239000001257 hydrogen Substances 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 150000001450 anions Chemical class 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 8
- 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 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- 239000003638 chemical reducing agent Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 150000003951 lactams Chemical class 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 238000002390 rotary evaporation Methods 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 230000027455 binding Effects 0.000 description 6
- 229960001340 histamine Drugs 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 6
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 229910021529 ammonia Inorganic materials 0.000 description 5
- 239000011260 aqueous acid Substances 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 5
- 238000010828 elution Methods 0.000 description 5
- 239000012280 lithium aluminium hydride Substances 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- 229910000564 Raney nickel Inorganic materials 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 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 4
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 3
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- 239000002841 Lewis acid Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000007868 Raney catalyst Substances 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 3
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 3
- 229910000085 borane Inorganic materials 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
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- 239000000284 extract Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- RCBVKBFIWMOMHF-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O RCBVKBFIWMOMHF-UHFFFAOYSA-L 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 150000007517 lewis acids Chemical class 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 239000012047 saturated solution Substances 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- LOIYMIARKYCTBW-OWOJBTEDSA-N trans-urocanic acid Chemical compound OC(=O)\C=C\C1=CNC=N1 LOIYMIARKYCTBW-OWOJBTEDSA-N 0.000 description 3
- UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- 102000000543 Histamine Receptors Human genes 0.000 description 2
- 108010002059 Histamine Receptors Proteins 0.000 description 2
- 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 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- LINDOXZENKYESA-UHFFFAOYSA-N TMG Natural products CNC(N)=NC LINDOXZENKYESA-UHFFFAOYSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 201000002380 X-linked amelogenesis imperfecta hypoplastic/hypomaturation 2 Diseases 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
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- 125000003158 alcohol group Chemical group 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
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- 230000003197 catalytic effect Effects 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 229940125936 compound 42 Drugs 0.000 description 2
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 238000003821 enantio-separation Methods 0.000 description 2
- 239000012259 ether extract Substances 0.000 description 2
- 239000002024 ethyl acetate extract Substances 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 239000011539 homogenization buffer Substances 0.000 description 2
- 150000002431 hydrogen Chemical group 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 206010022437 insomnia Diseases 0.000 description 2
- YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 2
- IHLVCKWPAMTVTG-UHFFFAOYSA-N lithium;carbanide Chemical compound [Li+].[CH3-] IHLVCKWPAMTVTG-UHFFFAOYSA-N 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000000463 material Substances 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/14—Decongestants or antiallergics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Ophthalmology & Optometry (AREA)
- Anesthesiology (AREA)
- Hospice & Palliative Care (AREA)
- Pulmonology (AREA)
- Rheumatology (AREA)
- Nutrition Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US80978191A | 1991-12-18 | 1991-12-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ246441A true NZ246441A (en) | 1996-02-27 |
Family
ID=25202205
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ246441A NZ246441A (en) | 1991-12-18 | 1992-12-17 | Imidazol or imidazolalkyl substituted with a 4 or 5 membered nitrogen containing heterocycle, preparation and pharmaceutical compositions thereof |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US5463074A (enExample) |
| EP (1) | EP0618913B1 (enExample) |
| JP (1) | JPH07121939B2 (enExample) |
| KR (1) | KR0142802B1 (enExample) |
| AT (1) | ATE141269T1 (enExample) |
| AU (1) | AU671092B2 (enExample) |
| CA (1) | CA2129679C (enExample) |
| DE (1) | DE69212844T2 (enExample) |
| DK (1) | DK0618913T3 (enExample) |
| ES (1) | ES2090956T3 (enExample) |
| GR (1) | GR3021464T3 (enExample) |
| HK (1) | HK31397A (enExample) |
| IL (1) | IL104125A (enExample) |
| MX (1) | MX9207393A (enExample) |
| MY (1) | MY110108A (enExample) |
| NZ (1) | NZ246441A (enExample) |
| SG (1) | SG44510A1 (enExample) |
| TW (1) | TW268950B (enExample) |
| WO (1) | WO1993012108A1 (enExample) |
| ZA (1) | ZA929788B (enExample) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5633250A (en) * | 1991-12-18 | 1997-05-27 | Schering Corporation | Imidazoylalkyl substituted with a six or seven membered heterocyclic ring containing two nitrogen atoms |
| FR2732017B1 (fr) * | 1995-03-21 | 2000-09-22 | Inst Nat Sante Rech Med | Nouveaux derives de l'imidazole antagonistes et/ou agonistes du recepteur h3 de l'histamine, leur preparation et leurs applications therapeutiques |
| JPH11508540A (ja) * | 1995-06-29 | 1999-07-27 | ノボ ノルディスク アクティーゼルスカブ | 新規の置換アザ環式またはアザ二環式化合物 |
| AU715603B2 (en) * | 1996-04-03 | 2000-02-03 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| JP2000507597A (ja) * | 1996-04-03 | 2000-06-20 | メルク エンド カンパニー インコーポレーテッド | ファルネシルタンパク質トランスフェラーゼ阻害剤 |
| US6072057A (en) * | 1996-06-06 | 2000-06-06 | Gliatech Inc. | 1H-4(5)-cyclo-substituted imidazole derivatives as histamine H3 receptor agents |
| US6407132B1 (en) | 1997-07-25 | 2002-06-18 | James Black Foundation Limited | Substituted imidazole derivatives and their use as histamine H3 receptor ligands |
| US6034251A (en) * | 1997-11-07 | 2000-03-07 | Schering Corporation | Phenyl-alkyl-imidazoles |
| EP1028956A1 (en) * | 1997-11-07 | 2000-08-23 | Schering Corporation | Imidazoylalkyl substituted with a five, six or seven membered heterocyclic ring containing one nitrogen atom |
| US5990147A (en) * | 1997-11-07 | 1999-11-23 | Schering Corporation | H3 receptor ligands of the phenyl-alkyl-imidazoles type |
| US6028095A (en) * | 1998-10-15 | 2000-02-22 | Warner-Lambert Company | Treatment of inflammatory bowel disease using histamine H3 -receptor agonists |
| US6133291A (en) * | 1998-10-16 | 2000-10-17 | Schering Corporation | N-(imidazolylalkyl)substituted cyclic amines as histamine-H3 agonists or antagonists |
| US6100279A (en) * | 1998-11-05 | 2000-08-08 | Schering Corporation | Imidazoylalkyl substituted with a five, six or seven membered heterocyclic ring containing one nitrogen atom |
| JP2002534511A (ja) | 1999-01-18 | 2002-10-15 | ノボ ノルディスク アクティーゼルスカブ | 置換型イミダゾール、それらの調製及び使用 |
| US6908926B1 (en) | 1999-04-16 | 2005-06-21 | Novo Nordisk A/S | Substituted imidazoles, their preparation and use |
| GB9924941D0 (en) * | 1999-10-22 | 1999-12-22 | Univ Manchester | Treatment of dyskinesia |
| US6610721B2 (en) | 2000-03-17 | 2003-08-26 | Novo Nordisk A/S | Imidazo heterocyclic compounds |
| US6437147B1 (en) | 2000-03-17 | 2002-08-20 | Novo Nordisk | Imidazole compounds |
| PE20020507A1 (es) | 2000-10-17 | 2002-06-25 | Schering Corp | Compuestos no-imidazoles como antagonistas del receptor histamina h3 |
| AU2002253929A1 (en) | 2001-02-08 | 2002-09-24 | Schering Corporation | Use of dual h3/m2 antagonists with a bipiperidinic structure in the treatment of cognition deficit disorders |
| WO2002072570A2 (en) * | 2001-03-13 | 2002-09-19 | Schering Corporation | Non-imidazole compounds as histamine h3 antagonists |
| FR2827863A1 (fr) * | 2001-07-27 | 2003-01-31 | Sanofi Synthelabo | Derives d'aminoalkylimidazole, leur preparation et leur utilisation en therapeutique |
| US7332508B2 (en) * | 2002-12-18 | 2008-02-19 | Novo Nordisk A/S | Substituted homopiperidine, piperidine or pyrrolidine derivatives |
| GB0505969D0 (en) | 2005-03-23 | 2005-04-27 | Novartis Ag | Organic compounds |
| EP1707203A1 (en) | 2005-04-01 | 2006-10-04 | Bioprojet | Treatment of parkinson's disease obstructive sleep apnea, dementia with lewy bodies, vascular dementia with non-imidazole alkylamines histamine H3- receptor ligands |
| EP1717233A1 (en) * | 2005-04-29 | 2006-11-02 | Bioprojet | Histamine H3-receptor ligands and their therapeutic application |
| EP1717235A3 (en) | 2005-04-29 | 2007-02-28 | Bioprojet | Phenoxypropylpiperidines and -pyrrolidines and their use as histamine H3-receptor ligands |
| GB0514203D0 (en) | 2005-07-11 | 2005-08-17 | Novartis Ag | Organic compounds |
| PE20110117A1 (es) | 2005-12-30 | 2011-03-07 | Novartis Ag | Derivados de 3,5-piridina como inhibidores de renina |
| NZ582098A (en) | 2007-06-25 | 2012-03-30 | Novartis Ag | N5-(2-ethoxyethyl)-n3-(2-pyridinyl)-3,5-piperidinedicarboxamide derivatives for use as renin inhibitors |
| WO2013151982A1 (en) | 2012-04-03 | 2013-10-10 | Arena Pharmaceuticals, Inc. | Methods and compounds useful in treating pruritus, and methods for identifying such compounds |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2987522A (en) * | 1958-03-17 | 1961-06-06 | Petrolite Corp | Amidine products |
| US3491098A (en) * | 1967-05-29 | 1970-01-20 | Sterling Drug Inc | 1-((imidazolyl)-lower-alkyl)-4-substituted-piperazines |
| US3470197A (en) * | 1967-08-30 | 1969-09-30 | Miles Lab | 1-substituted derivatives of 3-ethyl-4 - (1-methylimidazolyl-(5)-methyl)-2-pyrrolidinone |
| US4011238A (en) * | 1972-07-26 | 1977-03-08 | Gruppo Lepetit S.P.A. | 2-imidazolidione derivatives |
| EP0003732B1 (en) * | 1978-02-01 | 1983-10-19 | The Wellcome Foundation Limited | Imidazole derivatives and salts thereof, their synthesis, and pharmaceutical formulations thereof |
| GR73560B (enExample) * | 1979-02-24 | 1984-03-15 | Pfizer | |
| DK151884C (da) * | 1979-03-07 | 1988-06-13 | Pfizer | Analogifremgangsmaade til fremstilling af 3-(1-imidazolylalkyl)indolderivater eller farmaceutisk acceptable syreadditionssalte deraf |
| US4404387A (en) * | 1980-09-17 | 1983-09-13 | The Upjohn Company | Aminoalkyl-substituted imidazoles |
| US4404382A (en) * | 1980-09-17 | 1983-09-13 | The Upjohn Company | Piperazinyl-substituted imidazoles |
| US4431653A (en) * | 1982-03-18 | 1984-02-14 | Hoffmann-La Roche Inc. | Penicillanic acid derivatives |
| DE3313073A1 (de) * | 1983-04-12 | 1984-10-18 | Bayer Ag, 5090 Leverkusen | 1-azolyl-3-pyrazolyl-2-propanol-derivate, verfahren zu ihrer herstellung und ihre verwendung als fungizide |
| US4581370A (en) * | 1983-07-12 | 1986-04-08 | Schering A.G. | Antiarrhythmic imidazoliums |
| DK704488D0 (da) * | 1988-12-19 | 1988-12-19 | Novo Industri As | Nye n-substituerede azaheterocykliske carboxylsyrer |
| FR2579596B1 (fr) * | 1985-03-26 | 1987-11-20 | Inst Nat Sante Rech Med | (imidazolyl-4) piperidines, leur preparation et leur application en therapeutique |
| FR2586562B1 (fr) * | 1985-09-02 | 1989-03-10 | Inst Nat Sante Rech Med | Composition pharmaceutique contenant de l'a-methylhistamine |
| US5010075A (en) * | 1987-04-24 | 1991-04-23 | Syntex Pharmaceuticals Ltd. | Substituted imidazolyl-alkyl-piperazine and -diazepine derivatives |
| US4935417A (en) * | 1987-04-24 | 1990-06-19 | Syntex Pharmaceuticals Ltd. | Sustituted imidazolyl-alkyl-piperazine and -diazepine derivatives for treating cerebrovascular disease |
| US5091428A (en) * | 1987-04-24 | 1992-02-25 | Syntex Pharmaceuticals, Ltd. | Substituted imidazolyl-alkyl-piperazine and -diazepine derivatives |
| DE3811574A1 (de) * | 1988-03-31 | 1989-10-19 | Schering Ag | N-substituierte imidazole, verfahren zu ihrer herstellung sowie ihre verwendung in arzneimitteln |
| FR2630328B1 (fr) * | 1988-04-22 | 1990-08-24 | Inst Nat Sante Rech Med | Derive de l'histamine, sa preparation et son application en therapeutique |
| US4925851A (en) * | 1989-05-23 | 1990-05-15 | Sandoz Pharmaceuticals Corp. | 2- or 4-substituted-[2-(1H-imidazol-1-yl)ethyl]piperidines |
| US5264449A (en) * | 1989-11-13 | 1993-11-23 | Allergan, Inc. | N-substituted derivatives of 3R,4R-ethyl-[(1-methyl-1H-imidazol-5-yl)methyl]-2-pyrrolidinone |
| US5066663A (en) * | 1990-05-21 | 1991-11-19 | Warner-Lambert Company | Substituted-hetero-cyclopentanones and cyclopentenones and derivatives thereof acting at muscarinic receptors |
| WO1993020061A1 (en) * | 1992-04-01 | 1993-10-14 | The University Of Toledo | 4-[4'-piperidinyl or 3'-pirrolidinyl] substituted imidazoles as h3-receptor antagonists and therapeutic uses thereof |
-
1992
- 1992-12-17 ES ES93901329T patent/ES2090956T3/es not_active Expired - Lifetime
- 1992-12-17 MY MYPI92002334A patent/MY110108A/en unknown
- 1992-12-17 TW TW081110144A patent/TW268950B/zh active
- 1992-12-17 US US08/244,851 patent/US5463074A/en not_active Expired - Fee Related
- 1992-12-17 ZA ZA929788A patent/ZA929788B/xx unknown
- 1992-12-17 AT AT93901329T patent/ATE141269T1/de not_active IP Right Cessation
- 1992-12-17 MX MX9207393A patent/MX9207393A/es not_active IP Right Cessation
- 1992-12-17 CA CA002129679A patent/CA2129679C/en not_active Expired - Fee Related
- 1992-12-17 WO PCT/US1992/010743 patent/WO1993012108A1/en not_active Ceased
- 1992-12-17 SG SG1996001200A patent/SG44510A1/en unknown
- 1992-12-17 IL IL10412592A patent/IL104125A/xx not_active IP Right Cessation
- 1992-12-17 DK DK93901329.8T patent/DK0618913T3/da active
- 1992-12-17 EP EP93901329A patent/EP0618913B1/en not_active Expired - Lifetime
- 1992-12-17 NZ NZ246441A patent/NZ246441A/en unknown
- 1992-12-17 AU AU32773/93A patent/AU671092B2/en not_active Ceased
- 1992-12-17 DE DE69212844T patent/DE69212844T2/de not_active Expired - Fee Related
- 1992-12-17 JP JP5511100A patent/JPH07121939B2/ja not_active Expired - Fee Related
- 1992-12-27 KR KR94701079A patent/KR0142802B1/ko not_active Expired - Fee Related
-
1996
- 1996-10-24 GR GR960402819T patent/GR3021464T3/el unknown
-
1997
- 1997-03-13 HK HK31397A patent/HK31397A/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| JPH07121939B2 (ja) | 1995-12-25 |
| WO1993012108A1 (en) | 1993-06-24 |
| AU671092B2 (en) | 1996-08-15 |
| KR940703826A (enExample) | 1994-12-12 |
| ZA929788B (en) | 1993-06-22 |
| DK0618913T3 (da) | 1996-10-14 |
| US5463074A (en) | 1995-10-31 |
| MX9207393A (es) | 1994-06-30 |
| CA2129679C (en) | 2000-05-09 |
| IL104125A0 (en) | 1993-05-13 |
| KR0142802B1 (en) | 1998-07-15 |
| SG44510A1 (en) | 1997-12-19 |
| TW268950B (enExample) | 1996-01-21 |
| AU3277393A (en) | 1993-07-19 |
| JPH06511009A (ja) | 1994-12-08 |
| HK31397A (en) | 1997-03-21 |
| MY110108A (en) | 1998-01-27 |
| GR3021464T3 (en) | 1997-01-31 |
| EP0618913A1 (en) | 1994-10-12 |
| DE69212844T2 (de) | 1997-01-09 |
| ATE141269T1 (de) | 1996-08-15 |
| ES2090956T3 (es) | 1996-10-16 |
| CA2129679A1 (en) | 1993-06-24 |
| DE69212844D1 (de) | 1996-09-19 |
| EP0618913B1 (en) | 1996-08-14 |
| IL104125A (en) | 2000-08-31 |
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