FI81795C - Foerfarande foer framstaellning av substituerade isokinolinderivat. - Google Patents
Foerfarande foer framstaellning av substituerade isokinolinderivat. Download PDFInfo
- Publication number
- FI81795C FI81795C FI841992A FI841992A FI81795C FI 81795 C FI81795 C FI 81795C FI 841992 A FI841992 A FI 841992A FI 841992 A FI841992 A FI 841992A FI 81795 C FI81795 C FI 81795C
- Authority
- FI
- Finland
- Prior art keywords
- methyl
- formula
- dimethoxy
- dimethoxyphenyl
- isoquinoline
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 claims abstract description 85
- 150000003839 salts Chemical class 0.000 claims abstract description 33
- 239000002253 acid Substances 0.000 claims abstract description 17
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 4
- 125000005059 halophenyl group Chemical group 0.000 claims abstract description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 72
- 238000002360 preparation method Methods 0.000 claims description 45
- 239000000203 mixture Substances 0.000 claims description 38
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 31
- 238000000034 method Methods 0.000 claims description 30
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 27
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 23
- 230000008569 process Effects 0.000 claims description 8
- PWZXTLHDGIBNLG-UHFFFAOYSA-N 1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxy-4-[[4-(2-methoxyphenyl)piperazin-1-yl]methyl]isoquinoline Chemical compound C1=C(OC)C(OC)=CC=C1CC(C1=CC(OC)=C(OC)C=C11)=NC=C1CN1CCN(C=2C(=CC=CC=2)OC)CC1 PWZXTLHDGIBNLG-UHFFFAOYSA-N 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000001204 N-oxides Chemical class 0.000 claims description 4
- 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- 230000001590 oxidative effect Effects 0.000 claims description 3
- 102100034184 Macrophage scavenger receptor types I and II Human genes 0.000 claims 1
- 101710134306 Macrophage scavenger receptor types I and II Proteins 0.000 claims 1
- 150000002537 isoquinolines Chemical class 0.000 abstract description 2
- 201000006474 Brain Ischemia Diseases 0.000 abstract 1
- 230000002490 cerebral effect Effects 0.000 abstract 1
- 208000031225 myocardial ischemia Diseases 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 167
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 147
- 239000000243 solution Substances 0.000 description 67
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- -1 for example Chemical group 0.000 description 29
- 239000007787 solid Substances 0.000 description 28
- 239000000460 chlorine Substances 0.000 description 25
- 238000004458 analytical method Methods 0.000 description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- 238000001953 recrystallisation Methods 0.000 description 18
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 17
- 238000001914 filtration Methods 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 239000003960 organic solvent Substances 0.000 description 15
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
- 239000002585 base Substances 0.000 description 13
- 238000001704 evaporation Methods 0.000 description 13
- 229910052938 sodium sulfate Inorganic materials 0.000 description 13
- 235000011152 sodium sulphate Nutrition 0.000 description 13
- 125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 12
- 229940126062 Compound A Drugs 0.000 description 12
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000013078 crystal Substances 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- BLOBSQVTGXLIMU-UHFFFAOYSA-N 4-(chloromethyl)-1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxyisoquinoline Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=C(CCl)C2=CC(OC)=C(OC)C=C12 BLOBSQVTGXLIMU-UHFFFAOYSA-N 0.000 description 11
- 230000008020 evaporation Effects 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 229910052786 argon Inorganic materials 0.000 description 10
- 238000002425 crystallisation Methods 0.000 description 10
- 230000008025 crystallization Effects 0.000 description 10
- 229910052757 nitrogen Inorganic materials 0.000 description 10
- 239000012044 organic layer Substances 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 239000000538 analytical sample Substances 0.000 description 8
- 239000003610 charcoal Substances 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 8
- 239000012458 free base Substances 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- DDJGTWQLLMFDRX-UHFFFAOYSA-N [1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxyisoquinolin-4-yl]methanol Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=C(CO)C2=CC(OC)=C(OC)C=C12 DDJGTWQLLMFDRX-UHFFFAOYSA-N 0.000 description 7
- 238000009833 condensation Methods 0.000 description 6
- 230000005494 condensation Effects 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000010828 elution Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- 230000002792 vascular Effects 0.000 description 6
- KKRUMDFVRZXSAR-UHFFFAOYSA-N 1-(2-methoxyphenyl)-1-oxidopiperazin-1-ium Chemical compound COC1=CC=CC=C1[N+]1([O-])CCNCC1 KKRUMDFVRZXSAR-UHFFFAOYSA-N 0.000 description 5
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 5
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 5
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 5
- 239000006260 foam Substances 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 4
- KWLIUCFGAPCDRP-UHFFFAOYSA-N 4-(chloromethyl)-1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxy-2-oxidoisoquinolin-2-ium Chemical compound C1=C(OC)C(OC)=CC=C1CC1=[N+]([O-])C=C(CCl)C2=CC(OC)=C(OC)C=C12 KWLIUCFGAPCDRP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- RIIRKISDUWPKTG-UHFFFAOYSA-N ethyl 1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxy-3,4-dihydroisoquinoline-4-carboxylate;hydrochloride Chemical compound Cl.C12=CC(OC)=C(OC)C=C2C(C(=O)OCC)CN=C1CC1=CC=C(OC)C(OC)=C1 RIIRKISDUWPKTG-UHFFFAOYSA-N 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- YQYYMKVORCMXLH-UHFFFAOYSA-N methyl 1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxy-3,4-dihydroisoquinoline-4-carboxylate hydrochloride Chemical compound Cl.COC(=O)C1CN=C(Cc2ccc(OC)c(OC)c2)c2cc(OC)c(OC)cc12 YQYYMKVORCMXLH-UHFFFAOYSA-N 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 239000002002 slurry Substances 0.000 description 4
- VINAFENBIMPOAC-UHFFFAOYSA-N 1-(3,4-dimethoxyphenyl)-6,7-dimethoxy-3-methyl-4-[(4-phenylpiperidin-1-yl)methyl]isoquinoline Chemical compound COC=1C=C2C(=C(N=C(C2=CC=1OC)C1=CC(=C(C=C1)OC)OC)C)CN1CCC(CC1)C1=CC=CC=C1 VINAFENBIMPOAC-UHFFFAOYSA-N 0.000 description 3
- VFEZJMYGIZKDKC-UHFFFAOYSA-N 2-(dibenzylamino)-n-(2-methoxyphenyl)acetamide Chemical compound COC1=CC=CC=C1NC(=O)CN(CC=1C=CC=CC=1)CC1=CC=CC=C1 VFEZJMYGIZKDKC-UHFFFAOYSA-N 0.000 description 3
- RZIAABRFQASVSW-UHFFFAOYSA-N Isoquinoline N-oxide Chemical compound C1=CC=CC2=C[N+]([O-])=CC=C21 RZIAABRFQASVSW-UHFFFAOYSA-N 0.000 description 3
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 238000007865 diluting Methods 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 235000019260 propionic acid Nutrition 0.000 description 3
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- DJWNFMMYIQIDBH-UHFFFAOYSA-N tert-butyl 4-(2-methoxyphenyl)piperazine-1-carboxylate Chemical compound COC1=CC=CC=C1N1CCN(C(=O)OC(C)(C)C)CC1 DJWNFMMYIQIDBH-UHFFFAOYSA-N 0.000 description 3
- KMOVTNRHFITJGW-UHFFFAOYSA-N 1-(2-methoxyphenyl)piperazin-2-one;hydrochloride Chemical compound Cl.COC1=CC=CC=C1N1C(=O)CNCC1 KMOVTNRHFITJGW-UHFFFAOYSA-N 0.000 description 2
- VNZLQLYBRIOLFZ-UHFFFAOYSA-N 1-(2-methoxyphenyl)piperazine Chemical compound COC1=CC=CC=C1N1CCNCC1 VNZLQLYBRIOLFZ-UHFFFAOYSA-N 0.000 description 2
- QUJUYIYPUHQVBI-UHFFFAOYSA-N 1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxy-3,4-dihydroisoquinoline-4-carboxylic acid Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NCC(C(O)=O)C2=CC(OC)=C(OC)C=C12 QUJUYIYPUHQVBI-UHFFFAOYSA-N 0.000 description 2
- WFOSLWGAWWVZDX-UHFFFAOYSA-N 1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxy-4-[(4-phenylpiperazin-1-yl)methyl]isoquinoline Chemical compound C1=C(OC)C(OC)=CC=C1CC(C1=CC(OC)=C(OC)C=C11)=NC=C1CN1CCN(C=2C=CC=CC=2)CC1 WFOSLWGAWWVZDX-UHFFFAOYSA-N 0.000 description 2
- MDTAUMQIDZFHIZ-UHFFFAOYSA-N 1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxy-4-[[4-(2-methylphenyl)piperazin-1-yl]methyl]isoquinoline Chemical compound C1=C(OC)C(OC)=CC=C1CC(C1=CC(OC)=C(OC)C=C11)=NC=C1CN1CCN(C=2C(=CC=CC=2)C)CC1 MDTAUMQIDZFHIZ-UHFFFAOYSA-N 0.000 description 2
- SGFWTTIKOOLHND-UHFFFAOYSA-N 1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxyisoquinoline-4-carboxylic acid Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=C(C(O)=O)C2=CC(OC)=C(OC)C=C12 SGFWTTIKOOLHND-UHFFFAOYSA-N 0.000 description 2
- KDKGWGUUUVROTO-UHFFFAOYSA-N 1-hydroxypiperazine Chemical compound ON1CCNCC1 KDKGWGUUUVROTO-UHFFFAOYSA-N 0.000 description 2
- QBJIMTPENIGDOG-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)acetyl chloride Chemical compound COC1=CC=C(CC(Cl)=O)C=C1OC QBJIMTPENIGDOG-UHFFFAOYSA-N 0.000 description 2
- IVZDOGRRCXHDCZ-UHFFFAOYSA-N 4-benzyl-1-(2-methoxyphenyl)piperazin-2-one Chemical compound COC1=CC=CC=C1N1C(=O)CN(CC=2C=CC=CC=2)CC1 IVZDOGRRCXHDCZ-UHFFFAOYSA-N 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- UTBULQCHEUWJNV-UHFFFAOYSA-N 4-phenylpiperidine Chemical compound C1CNCCC1C1=CC=CC=C1 UTBULQCHEUWJNV-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 208000001953 Hypotension Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- JEDZLBFUGJTJGQ-UHFFFAOYSA-N [Na].COCCO[AlH]OCCOC Chemical compound [Na].COCCO[AlH]OCCOC JEDZLBFUGJTJGQ-UHFFFAOYSA-N 0.000 description 2
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 206010003119 arrhythmia Diseases 0.000 description 2
- 150000007514 bases Chemical class 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 229910000085 borane Inorganic materials 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 2
- 125000005805 dimethoxy phenyl group Chemical group 0.000 description 2
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 210000001198 duodenum Anatomy 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- WUAXWQRULBZETB-UHFFFAOYSA-N homoveratric acid Chemical compound COC1=CC=C(CC(O)=O)C=C1OC WUAXWQRULBZETB-UHFFFAOYSA-N 0.000 description 2
- 230000036543 hypotension Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- PNZBWOINPDFLGY-UHFFFAOYSA-N methyl 1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxyisoquinoline-4-carboxylate Chemical compound C12=CC(OC)=C(OC)C=C2C(C(=O)OC)=CN=C1CC1=CC=C(OC)C(OC)=C1 PNZBWOINPDFLGY-UHFFFAOYSA-N 0.000 description 2
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- VZMZQIOEJUSLIX-UHFFFAOYSA-N methyl 3-amino-2-(3,4-dimethoxyphenyl)propanoate Chemical compound COC(=O)C(CN)C1=CC=C(OC)C(OC)=C1 VZMZQIOEJUSLIX-UHFFFAOYSA-N 0.000 description 1
- LRJUXBUTQCLSPE-UHFFFAOYSA-N methyl 3-amino-2-(3,4-dipropoxyphenyl)propanoate Chemical compound COC(C(C1=CC(=C(C=C1)OCCC)OCCC)CN)=O LRJUXBUTQCLSPE-UHFFFAOYSA-N 0.000 description 1
- SMUQFGGVLNAIOZ-UHFFFAOYSA-N methylquinoline Natural products C1=CC=CC2=NC(C)=CC=C21 SMUQFGGVLNAIOZ-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- IJXQMMYOYJWSDF-UHFFFAOYSA-N n',n'-dibenzyl-n-(2-methoxyphenyl)ethane-1,2-diamine Chemical compound COC1=CC=CC=C1NCCN(CC=1C=CC=CC=1)CC1=CC=CC=C1 IJXQMMYOYJWSDF-UHFFFAOYSA-N 0.000 description 1
- QEUMNQFVAMSSNS-UHFFFAOYSA-N n-benzyl-1-phenylmethanamine;hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C[NH2+]CC1=CC=CC=C1 QEUMNQFVAMSSNS-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
- 229960001597 nifedipine Drugs 0.000 description 1
- 229960000715 nimodipine Drugs 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- 239000004533 oil dispersion Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 229960001789 papaverine Drugs 0.000 description 1
- UNEIHNMKASENIG-UHFFFAOYSA-N para-chlorophenylpiperazine Chemical compound C1=CC(Cl)=CC=C1N1CCNCC1 UNEIHNMKASENIG-UHFFFAOYSA-N 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- WEYVCQFUGFRXOM-UHFFFAOYSA-N perazine Chemical compound C1CN(C)CCN1CCCN1C2=CC=CC=C2SC2=CC=CC=C21 WEYVCQFUGFRXOM-UHFFFAOYSA-N 0.000 description 1
- 229960002195 perazine Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- QAZCPUUJMFBNJO-UHFFFAOYSA-N pyrrolidin-2-one;sodium Chemical compound [Na].O=C1CCCN1 QAZCPUUJMFBNJO-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008327 renal blood flow Effects 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000035488 systolic blood pressure Effects 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 201000010875 transient cerebral ischemia Diseases 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- 210000002385 vertebral artery Anatomy 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/205—Radicals derived from carbonic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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
- A61P9/10—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/18—Aralkyl radicals
- C07D217/20—Aralkyl radicals with oxygen atoms directly attached to the aromatic ring of said aralkyl radical, e.g. papaverine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
- C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/06—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members
- C07D241/08—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/22—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with hetero atoms directly attached to ring nitrogen atoms
- C07D295/24—Oxygen atoms
-
- 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
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/496,327 US4544657A (en) | 1983-05-19 | 1983-05-19 | Substituted isoquinolines |
| US49632783 | 1983-05-19 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI841992A0 FI841992A0 (fi) | 1984-05-17 |
| FI841992A7 FI841992A7 (fi) | 1984-11-20 |
| FI81795B FI81795B (fi) | 1990-08-31 |
| FI81795C true FI81795C (fi) | 1990-12-10 |
Family
ID=23972146
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI841992A FI81795C (fi) | 1983-05-19 | 1984-05-17 | Foerfarande foer framstaellning av substituerade isokinolinderivat. |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US4544657A (en:Method) |
| EP (1) | EP0126480B1 (en:Method) |
| JP (1) | JPS59222478A (en:Method) |
| KR (1) | KR840009102A (en:Method) |
| AT (1) | ATE32072T1 (en:Method) |
| AU (1) | AU570044B2 (en:Method) |
| CA (1) | CA1243028A (en:Method) |
| DE (1) | DE3468875D1 (en:Method) |
| DK (1) | DK248484A (en:Method) |
| ES (1) | ES8601141A1 (en:Method) |
| FI (1) | FI81795C (en:Method) |
| GR (1) | GR82015B (en:Method) |
| HU (1) | HU192555B (en:Method) |
| IL (1) | IL71860A (en:Method) |
| MC (1) | MC1597A1 (en:Method) |
| NO (1) | NO159271C (en:Method) |
| NZ (1) | NZ208186A (en:Method) |
| PH (1) | PH19670A (en:Method) |
| PT (1) | PT78618A (en:Method) |
| ZA (1) | ZA843748B (en:Method) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5681954A (en) * | 1993-05-14 | 1997-10-28 | Daiichi Pharmaceutical Co., Ltd. | Piperazine derivatives |
| RU2124511C1 (ru) * | 1993-05-14 | 1999-01-10 | Фармасьютикал Ко., Лтд | Производные пиперазина |
| NZ295546A (en) * | 1994-10-05 | 1999-01-28 | Glaxo Wellcome Inc | Parenteral medicament containing n-{4-[2-1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)-ethyl]-phenyl}- 9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide, surfactant, and buffer |
| FR2840896B1 (fr) * | 2002-06-18 | 2005-04-08 | Sanofi Synthelabo | Phenyl-et pyridyl-piperazines, procede pour leur preparation et compositions pharmaceutiques les contenant |
| MX2008001292A (es) | 2005-07-29 | 2008-03-25 | Hoffmann La Roche | Nuevos derivados de indol-3-il-carbonil-piperidina y piperazina. |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE759443A (fr) * | 1970-09-15 | 1971-04-30 | I F L O Istituto Farmacologico | Nouveau derive papaverolinique et procede de preparation relatif |
| DE2818423A1 (de) * | 1978-04-27 | 1979-11-08 | Hoechst Ag | Neue isochinolinderivate und verfahren zu ihrer herstellung |
| IN154317B (en:Method) * | 1979-07-19 | 1984-10-13 | Andre Buzas | |
| DE3034001A1 (de) * | 1980-09-10 | 1982-04-22 | Hoechst Ag, 6000 Frankfurt | Isochinolinderivate, verfahren zu ihrer hersellung, sie enthaltende pharmazeutische zubereitungen und ihre verwendung |
-
1983
- 1983-05-19 US US06/496,327 patent/US4544657A/en not_active Expired - Fee Related
-
1984
- 1984-05-17 FI FI841992A patent/FI81795C/fi not_active IP Right Cessation
- 1984-05-17 CA CA000454531A patent/CA1243028A/en not_active Expired
- 1984-05-17 IL IL71860A patent/IL71860A/xx unknown
- 1984-05-17 GR GR74757A patent/GR82015B/el unknown
- 1984-05-17 NZ NZ208186A patent/NZ208186A/en unknown
- 1984-05-17 ZA ZA843748A patent/ZA843748B/xx unknown
- 1984-05-17 DK DK248484A patent/DK248484A/da not_active Application Discontinuation
- 1984-05-17 MC MC841707A patent/MC1597A1/fr unknown
- 1984-05-18 NO NO842003A patent/NO159271C/no unknown
- 1984-05-18 HU HU841916A patent/HU192555B/hu not_active IP Right Cessation
- 1984-05-18 AU AU28356/84A patent/AU570044B2/en not_active Ceased
- 1984-05-18 ES ES532603A patent/ES8601141A1/es not_active Expired
- 1984-05-18 PH PH30693A patent/PH19670A/en unknown
- 1984-05-18 KR KR1019840002721A patent/KR840009102A/ko not_active Ceased
- 1984-05-18 JP JP59098863A patent/JPS59222478A/ja active Pending
- 1984-05-18 PT PT78618A patent/PT78618A/pt not_active IP Right Cessation
- 1984-05-21 DE DE8484105777T patent/DE3468875D1/de not_active Expired
- 1984-05-21 EP EP84105777A patent/EP0126480B1/de not_active Expired
- 1984-05-21 AT AT84105777T patent/ATE32072T1/de not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| FI841992A7 (fi) | 1984-11-20 |
| ES532603A0 (es) | 1985-11-01 |
| ATE32072T1 (de) | 1988-02-15 |
| PT78618A (en) | 1984-06-01 |
| NO159271C (no) | 1988-12-14 |
| FI81795B (fi) | 1990-08-31 |
| HU192555B (en) | 1987-06-29 |
| ES8601141A1 (es) | 1985-11-01 |
| NO842003L (no) | 1984-11-20 |
| HUT34185A (en) | 1985-02-28 |
| FI841992A0 (fi) | 1984-05-17 |
| ZA843748B (en) | 1985-01-30 |
| MC1597A1 (fr) | 1985-05-09 |
| DK248484A (da) | 1984-11-20 |
| CA1243028A (en) | 1988-10-11 |
| AU570044B2 (en) | 1988-03-03 |
| US4544657A (en) | 1985-10-01 |
| IL71860A (en) | 1987-10-30 |
| KR840009102A (ko) | 1984-12-24 |
| AU2835684A (en) | 1984-11-22 |
| EP0126480B1 (de) | 1988-01-20 |
| JPS59222478A (ja) | 1984-12-14 |
| IL71860A0 (en) | 1984-09-30 |
| NZ208186A (en) | 1987-06-30 |
| EP0126480A1 (de) | 1984-11-28 |
| DK248484D0 (da) | 1984-05-17 |
| DE3468875D1 (en) | 1988-02-25 |
| GR82015B (en:Method) | 1984-12-12 |
| NO159271B (no) | 1988-09-05 |
| PH19670A (en) | 1986-06-09 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: F. HOFFMANN-LA ROCHE AG |