DD284678A5 - Verfahren zur herstellung von neuen cyclischen aminderivaten - Google Patents
Verfahren zur herstellung von neuen cyclischen aminderivaten Download PDFInfo
- Publication number
- DD284678A5 DD284678A5 DD88315962A DD31596288A DD284678A5 DD 284678 A5 DD284678 A5 DD 284678A5 DD 88315962 A DD88315962 A DD 88315962A DD 31596288 A DD31596288 A DD 31596288A DD 284678 A5 DD284678 A5 DD 284678A5
- Authority
- DD
- German Democratic Republic
- Prior art keywords
- methyl
- oxo
- tetrahydro
- dimethoxy
- group
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 150000001412 amines Chemical class 0.000 title description 3
- -1 cyclic amine Chemical class 0.000 claims abstract description 444
- 150000001875 compounds Chemical class 0.000 claims abstract description 55
- 239000002253 acid Substances 0.000 claims abstract description 34
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 13
- 150000001204 N-oxides Chemical class 0.000 claims abstract description 4
- 239000000460 chlorine Substances 0.000 claims description 228
- 125000005605 benzo group Chemical group 0.000 claims description 72
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 54
- 239000001257 hydrogen Substances 0.000 claims description 36
- 229910052739 hydrogen Inorganic materials 0.000 claims description 36
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 34
- 125000004432 carbon atom Chemical group C* 0.000 claims description 34
- 125000000217 alkyl group Chemical group 0.000 claims description 29
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
- 238000006243 chemical reaction Methods 0.000 claims description 23
- 239000002904 solvent Substances 0.000 claims description 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 125000002947 alkylene group Chemical group 0.000 claims description 15
- 125000005843 halogen group Chemical group 0.000 claims description 15
- 239000011541 reaction mixture Substances 0.000 claims description 15
- 239000003054 catalyst Substances 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 12
- UWYZHKAOTLEWKK-UHFFFAOYSA-N tetrahydro-isoquinoline Natural products C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 claims description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 9
- 238000005984 hydrogenation reaction Methods 0.000 claims description 9
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- 150000003254 radicals Chemical class 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 8
- 125000002071 phenylalkoxy group Chemical group 0.000 claims description 8
- 125000004434 sulfur atom Chemical group 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 150000001721 carbon Chemical group 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 7
- 150000007522 mineralic acids Chemical class 0.000 claims description 7
- 230000000269 nucleophilic effect Effects 0.000 claims description 7
- 150000007524 organic acids Chemical class 0.000 claims description 7
- 235000005985 organic acids Nutrition 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- 125000003282 alkyl amino group Chemical group 0.000 claims description 6
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 6
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 125000001072 heteroaryl group Chemical group 0.000 claims description 6
- 125000001041 indolyl group Chemical group 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 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 5
- 238000009835 boiling Methods 0.000 claims description 5
- 125000004122 cyclic group Chemical group 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 4
- YZCKVEUIGOORGS-UHFFFAOYSA-N Hydrogen atom Chemical compound [H] YZCKVEUIGOORGS-UHFFFAOYSA-N 0.000 claims description 4
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 claims description 4
- 229910052987 metal hydride Inorganic materials 0.000 claims description 4
- 150000004681 metal hydrides Chemical class 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000006239 protecting group Chemical group 0.000 claims description 4
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 4
- 230000010933 acylation Effects 0.000 claims description 3
- 238000005917 acylation reaction Methods 0.000 claims description 3
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000001680 trimethoxyphenyl group Chemical group 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000002619 bicyclic group Chemical group 0.000 claims description 2
- 229910000085 borane Inorganic materials 0.000 claims description 2
- 125000001589 carboacyl group Chemical group 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000005805 dimethoxy phenyl group Chemical group 0.000 claims description 2
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 2
- 125000002950 monocyclic group Chemical group 0.000 claims description 2
- 208000031225 myocardial ischemia Diseases 0.000 claims description 2
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- 150000003568 thioethers Chemical class 0.000 claims description 2
- 238000011282 treatment Methods 0.000 claims description 2
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims 2
- 239000005977 Ethylene Substances 0.000 claims 2
- DQFQCHIDRBIESA-UHFFFAOYSA-N 1-benzazepine Chemical compound N1C=CC=CC2=CC=CC=C12 DQFQCHIDRBIESA-UHFFFAOYSA-N 0.000 claims 1
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims 1
- 101100240545 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) nit-3 gene Proteins 0.000 claims 1
- 208000000260 Warts Diseases 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 230000008030 elimination Effects 0.000 claims 1
- 238000003379 elimination reaction Methods 0.000 claims 1
- 201000010153 skin papilloma Diseases 0.000 claims 1
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 18
- 238000004519 manufacturing process Methods 0.000 abstract description 7
- 230000000144 pharmacologic effect Effects 0.000 abstract description 5
- 230000001077 hypotensive effect Effects 0.000 abstract description 4
- 229910052740 iodine Inorganic materials 0.000 abstract description 3
- 238000002844 melting Methods 0.000 description 232
- 230000008018 melting Effects 0.000 description 232
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 187
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 168
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 152
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 126
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 90
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 78
- 239000012280 lithium aluminium hydride Substances 0.000 description 63
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 59
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 53
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 52
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 50
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 46
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 41
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 39
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 39
- 239000000741 silica gel Substances 0.000 description 39
- 229910002027 silica gel Inorganic materials 0.000 description 39
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 34
- 239000000243 solution Substances 0.000 description 33
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 30
- 239000003480 eluent Substances 0.000 description 27
- 229960000583 acetic acid Drugs 0.000 description 25
- 239000012362 glacial acetic acid Substances 0.000 description 25
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 239000012074 organic phase Substances 0.000 description 24
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 23
- 235000019341 magnesium sulphate Nutrition 0.000 description 23
- VSOJKDUWYQCWFM-UHFFFAOYSA-N 7,8-dihydro-6h-[1,3]dioxolo[4,5-g]isoquinolin-5-one Chemical compound C1=C2C(=O)NCCC2=CC2=C1OCO2 VSOJKDUWYQCWFM-UHFFFAOYSA-N 0.000 description 22
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 22
- 239000000203 mixture Substances 0.000 description 20
- 238000003756 stirring Methods 0.000 description 19
- 229910021529 ammonia Inorganic materials 0.000 description 17
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 17
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 16
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- 239000011701 zinc Substances 0.000 description 15
- 229910052725 zinc Inorganic materials 0.000 description 15
- QMEZUZOCLYUADC-UHFFFAOYSA-N hydrate;dihydrochloride Chemical compound O.Cl.Cl QMEZUZOCLYUADC-UHFFFAOYSA-N 0.000 description 14
- 239000005457 ice water Substances 0.000 description 14
- 125000003163 2-(2-naphthyl)ethyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(C([H])=C([H])C2=C1[H])C([H])([H])C([H])([H])* 0.000 description 12
- 230000000875 corresponding effect Effects 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 9
- 239000012071 phase Substances 0.000 description 9
- 125000005806 3,4,5-trimethoxybenzyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1C([H])([H])* 0.000 description 8
- MQKFSXLBPPCAGR-UHFFFAOYSA-N 6,7-dimethoxy-3,4-dihydro-2h-isoquinolin-1-one Chemical compound C1CNC(=O)C2=C1C=C(OC)C(OC)=C2 MQKFSXLBPPCAGR-UHFFFAOYSA-N 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
- 238000006722 reduction reaction Methods 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- 239000007868 Raney catalyst Substances 0.000 description 7
- 229910000564 Raney nickel Inorganic materials 0.000 description 7
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 7
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
- CKQQMPJQZXIYMJ-UHFFFAOYSA-N dihydrate;dihydrochloride Chemical compound O.O.Cl.Cl CKQQMPJQZXIYMJ-UHFFFAOYSA-N 0.000 description 7
- 230000007935 neutral effect Effects 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- WNLPAQFDNAVWLM-UHFFFAOYSA-N 2-(2-bromoethyl)-6-methoxynaphthalene Chemical compound C1=C(CCBr)C=CC2=CC(OC)=CC=C21 WNLPAQFDNAVWLM-UHFFFAOYSA-N 0.000 description 6
- HIBYPMTYUSTJDC-UHFFFAOYSA-N 3-(1h-indol-3-yl)propyl benzenesulfonate Chemical compound C=1NC2=CC=CC=C2C=1CCCOS(=O)(=O)C1=CC=CC=C1 HIBYPMTYUSTJDC-UHFFFAOYSA-N 0.000 description 6
- LTAGXVMHLFYRNK-UHFFFAOYSA-N 4-(2-bromoethyl)-1,2-dimethoxybenzene Chemical compound COC1=CC=C(CCBr)C=C1OC LTAGXVMHLFYRNK-UHFFFAOYSA-N 0.000 description 6
- ZWTYJECJAVZKCP-UHFFFAOYSA-N 6-(3-chloropropoxy)-1,2-dimethoxynaphthalene Chemical compound C1=C(OCCCCl)C=CC2=C(OC)C(OC)=CC=C21 ZWTYJECJAVZKCP-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 6
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000013543 active substance Substances 0.000 description 6
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 6
- 229910052700 potassium Inorganic materials 0.000 description 6
- 239000011591 potassium Substances 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- JZPDDOYOZALHFK-UHFFFAOYSA-N 1,2,3,4-tetrahydro-3-benzazepin-5-one Chemical compound O=C1CNCCC2=CC=CC=C12 JZPDDOYOZALHFK-UHFFFAOYSA-N 0.000 description 5
- STBYRSZXHDPASK-UHFFFAOYSA-N 1-(chloromethyl)-2-methylnaphthalene Chemical compound C1=CC=CC2=C(CCl)C(C)=CC=C21 STBYRSZXHDPASK-UHFFFAOYSA-N 0.000 description 5
- JSJWVMQXHQWPCG-UHFFFAOYSA-N 6,7-dimethyl-3,4-dihydro-2h-isoquinolin-1-one Chemical compound C1CNC(=O)C2=C1C=C(C)C(C)=C2 JSJWVMQXHQWPCG-UHFFFAOYSA-N 0.000 description 5
- 229920002261 Corn starch Polymers 0.000 description 5
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 5
- 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 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Substances OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 239000008120 corn starch Substances 0.000 description 5
- 229940093915 gynecological organic acid Drugs 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 5
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
-
- 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
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- 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
- 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
- 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
- C07D401/14—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 three or more hetero rings
-
- 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
- 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
- C07D403/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Gears, Cams (AREA)
- Valve-Gear Or Valve Arrangements (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Indole Compounds (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19873717561 DE3717561A1 (de) | 1987-05-25 | 1987-05-25 | Indol-, isochinolin- und benzazepinderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DD284678A5 true DD284678A5 (de) | 1990-11-21 |
Family
ID=6328351
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DD88315962A DD284678A5 (de) | 1987-05-25 | 1988-05-20 | Verfahren zur herstellung von neuen cyclischen aminderivaten |
Country Status (21)
| Country | Link |
|---|---|
| EP (1) | EP0292840B1 (https=) |
| JP (1) | JP2634190B2 (https=) |
| KR (1) | KR960009432B1 (https=) |
| AT (1) | ATE126225T1 (https=) |
| AU (1) | AU607765B2 (https=) |
| CA (2) | CA1330993C (https=) |
| DD (1) | DD284678A5 (https=) |
| DE (2) | DE3717561A1 (https=) |
| DK (1) | DK282188A (https=) |
| ES (1) | ES2076147T3 (https=) |
| FI (1) | FI94343C (https=) |
| GR (1) | GR3017550T3 (https=) |
| HU (1) | HU198201B (https=) |
| IE (1) | IE68842B1 (https=) |
| IL (1) | IL86477A (https=) |
| IN (1) | IN169514B (https=) |
| NO (1) | NO171017C (https=) |
| NZ (1) | NZ224756A (https=) |
| PT (1) | PT87567B (https=) |
| SU (1) | SU1561823A3 (https=) |
| ZA (1) | ZA883680B (https=) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3640641A1 (de) * | 1986-11-28 | 1988-07-14 | Thomae Gmbh Dr K | Neue heteroaromatische aminderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| DE3835291A1 (de) * | 1988-04-19 | 1989-11-02 | Bayer Ag | 1,3-disubstituierte pyrrolidine |
| US4902684A (en) * | 1988-06-20 | 1990-02-20 | E. R. Squibb & Sons, Inc. | Benzazepine and benzothiazepine derivatives |
| EP0351283A1 (fr) * | 1988-07-12 | 1990-01-17 | Synthelabo | Dérivés de [(pipéridinyl-4) méthyl]-2 dihydro-2,3 1H-isoindole et tétrahydro-2,3,4,5 1H-benzazépines, leur préparation et leur application en thérapeutique |
| IL89156A (en) * | 1988-07-12 | 1993-05-13 | Synthelabo | Derivatives of 2-((4-piperidinyl) methyl)- 1,2,3,4- tetrahydroisoquinoline, their preparation and their application in therapeutics |
| US4952692A (en) * | 1989-04-04 | 1990-08-28 | E. R. Squibb & Sons, Inc. | Benzazepine derivatives |
| US4946840A (en) * | 1989-04-06 | 1990-08-07 | E. R. Squibb & Sons, Inc. | Benzazepine and benzothiazepine derivatives |
| NZ235841A (en) * | 1989-10-27 | 1993-03-26 | Du Pont | (n-phthalimidoalkyl) piperidine derivatives and pharmaceutical compositions |
| ZA908641B (en) * | 1989-10-27 | 1992-06-24 | Du Pont | (n-phthalimidoalkyl)piperidines |
| US5356906A (en) * | 1989-10-27 | 1994-10-18 | The Du Pont Merck Pharmaceutical Company | (N-phthalimidoalkyl) piperidines useful as treatments for psychosis |
| EP0429341A3 (en) * | 1989-11-20 | 1991-11-13 | Rhone-Poulenc Sante | Heterocyclic derivatives, their preparation and pharmaceuticals containing them |
| US7166617B2 (en) * | 2000-02-29 | 2007-01-23 | Mitsubishi Pharma Corporation | Cyclic amide derivatives |
| KR100897642B1 (ko) | 2002-12-20 | 2009-05-14 | 글락소 그룹 리미티드 | 신경 장애 치료용 벤즈아제핀 유도체 |
| FR2868776B1 (fr) * | 2004-04-13 | 2008-04-18 | Servier Lab | Nouveau procede de synthese de derives de la 1,3-dihydro- 2h-3-benzazepin-2-one, et application a la synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
| JP5031745B2 (ja) * | 2005-08-12 | 2012-09-26 | アストラゼネカ アクチボラグ | 代謝型グルタミン酸受容体増強性イソインドロン |
| AR059898A1 (es) | 2006-03-15 | 2008-05-07 | Janssen Pharmaceutica Nv | Derivados de 3-ciano-piridona 1,4-disustituida y su uso como moduladores alostericos de los receptores mglur2 |
| TW200900065A (en) | 2007-03-07 | 2009-01-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-pyridinyloxy-phenyl)-pyridin-2-one derivatives |
| TW200845978A (en) | 2007-03-07 | 2008-12-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives |
| SI2203439T1 (sl) | 2007-09-14 | 2011-05-31 | Ortho Mcneil Janssen Pharm | 1',3'-disubstituirani 4-fenil-3,4,5,6-tetrahidro-2H-1'H-(1,4')bipiridinil-2'-oni |
| EP2344470B1 (en) | 2008-09-02 | 2013-11-06 | Janssen Pharmaceuticals, Inc. | 3-azabicyclo[3.1.0]hexyl derivatives as modulators of metabotropic glutamate receptors |
| JP5690277B2 (ja) | 2008-11-28 | 2015-03-25 | ジャンセン ファーマシューティカルズ， インコーポレイテッド． | 代謝型グルタミン酸受容体の調節因子としてのインドールおよびベンゾオキサジン誘導体 |
| BRPI1010831A2 (pt) | 2009-05-12 | 2016-04-05 | Addex Pharmaceuticals Sa | derivados de 1,2,4-triazolo[4,3-a]piridina e seu como moduladores alostéricos positivos de receptores de mglur2 |
| CN102439008B (zh) | 2009-05-12 | 2015-04-29 | 杨森制药有限公司 | 1,2,4-三唑并[4,3-a]吡啶衍生物及其用于治疗或预防神经和精神病症的用途 |
| MY153913A (en) | 2009-05-12 | 2015-04-15 | Janssen Pharmaceuticals Inc | 7-aryl-1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
| ES2536433T3 (es) | 2010-11-08 | 2015-05-25 | Janssen Pharmaceuticals, Inc. | Derivados de 1,2,4-triazolo[4,3-a]piridina y su uso como moduladores alostéricos positivos de receptores mGluR2 |
| AU2011328203B2 (en) | 2010-11-08 | 2015-03-19 | Janssen Pharmaceuticals, Inc. | 1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mGluR2 receptors |
| WO2013024036A1 (en) | 2011-08-12 | 2013-02-21 | Boehringer Ingelheim Vetmedica Gmbh | Funny current (if) inhibitors for use in a method of treating and preventing heart failure in feline |
| JO3368B1 (ar) | 2013-06-04 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 6، 7- ثاني هيدرو بيرازولو [5،1-a] بيرازين- 4 (5 يد)- اون واستخدامها بصفة منظمات تفارغية سلبية لمستقبلات ميجلور 2 |
| JO3367B1 (ar) | 2013-09-06 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 2،1، 4- ثلاثي زولو [3،4-a] بيريدين واستخدامها بصفة منظمات تفارغية موجبة لمستقبلات ميجلور 2 |
| MX386697B (es) | 2014-01-21 | 2025-03-19 | Janssen Pharmaceutica Nv | Combinaciones que comprenden agonistas ortostericos o moduladores alostericos positivos del receptor glutamatergico metabotropico de subtipo 2 y su uso |
| ME03518B (me) | 2014-01-21 | 2020-04-20 | Janssen Pharmaceutica Nv | Kombinacije koje obuhvataju pozitivne alosterične modulatore ili ortosterične agoniste metabotropnog glutamatergičnog receptora podtipa 2 i njihova primjena |
| JP6931456B2 (ja) * | 2017-04-03 | 2021-09-08 | 川崎化成工業株式会社 | ２−ハロアルコキシ−６−置換オキシナフタレン化合物及び２−ハロアルコキシ−６−置換オキシナフタレン化合物を含有する光重合増感剤 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2639718C2 (de) * | 1976-09-03 | 1987-03-05 | Dr. Karl Thomae Gmbh, 7950 Biberach | 1-[6,7-Dimethoxy-3,4-dihydro-2H-isochinolin-1-on-2-yl]-3-[N-methyl-N-(2-(3,4-dimethoxy-phenyl)-äthyl)-amino]-propan, dessen physiologisch verträgliche Säureadditionssalze und diese Verbindungen enthaltende Arzneimittel |
| DE3119874A1 (de) * | 1981-05-19 | 1982-12-09 | Dr. Karl Thomae Gmbh, 7950 Biberach | "benzazepinderivate, ihre herstellung und ihre verwendung als arzneimittel" |
| DE3418271A1 (de) * | 1984-05-17 | 1985-11-21 | Dr. Karl Thomae Gmbh, 7950 Biberach | Neue benzazepinderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| DE3418270A1 (de) * | 1984-05-17 | 1985-11-21 | Dr. Karl Thomae Gmbh, 7950 Biberach | Neue aminotetralinderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| DE3541811A1 (de) * | 1985-11-27 | 1987-06-04 | Thomae Gmbh Dr K | Neue cyclische aminderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| EP0306375A1 (fr) * | 1987-08-07 | 1989-03-08 | Synthelabo | Dérivés de[(pipéridinyl-4)méthyl]-2 tétrahydro-1,2,3,4 isoquinoléine, leur préparation et leur application en thérapeutique |
| IL89156A (en) * | 1988-07-12 | 1993-05-13 | Synthelabo | Derivatives of 2-((4-piperidinyl) methyl)- 1,2,3,4- tetrahydroisoquinoline, their preparation and their application in therapeutics |
| FR2686339B1 (fr) * | 1992-01-22 | 1994-03-11 | Adir Cie | Nouveaux amides et sulfonamides naphtaleniques, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent. |
-
1987
- 1987-05-25 DE DE19873717561 patent/DE3717561A1/de not_active Ceased
-
1988
- 1988-05-17 EP EP88107867A patent/EP0292840B1/de not_active Expired - Lifetime
- 1988-05-19 IN IN400/CAL/88A patent/IN169514B/en unknown
- 1988-05-20 CA CA000567464A patent/CA1330993C/en not_active Expired - Fee Related
- 1988-05-20 DD DD88315962A patent/DD284678A5/de not_active IP Right Cessation
- 1988-05-20 CA CA000567453A patent/CA1287226C/en not_active Expired - Lifetime
- 1988-05-23 FI FI882418A patent/FI94343C/fi not_active IP Right Cessation
- 1988-05-23 NZ NZ224756A patent/NZ224756A/xx unknown
- 1988-05-24 DK DK282188A patent/DK282188A/da not_active Application Discontinuation
- 1988-05-24 ZA ZA883680A patent/ZA883680B/xx unknown
- 1988-05-24 DE DE3854280T patent/DE3854280D1/de not_active Expired - Fee Related
- 1988-05-24 AT AT88107867T patent/ATE126225T1/de not_active IP Right Cessation
- 1988-05-24 JP JP63126910A patent/JP2634190B2/ja not_active Expired - Lifetime
- 1988-05-24 KR KR88006072A patent/KR960009432B1/ko not_active Expired - Fee Related
- 1988-05-24 ES ES88107867T patent/ES2076147T3/es not_active Expired - Lifetime
- 1988-05-24 IL IL86477A patent/IL86477A/xx unknown
- 1988-05-24 SU SU884355736A patent/SU1561823A3/ru active
- 1988-05-24 NO NO882258A patent/NO171017C/no unknown
- 1988-05-24 PT PT87567A patent/PT87567B/pt not_active IP Right Cessation
- 1988-05-24 HU HU882647A patent/HU198201B/hu not_active IP Right Cessation
- 1988-05-24 IE IE155988A patent/IE68842B1/en not_active IP Right Cessation
- 1988-05-24 AU AU16562/88A patent/AU607765B2/en not_active Ceased
-
1995
- 1995-09-28 GR GR950402663T patent/GR3017550T3/el unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| ENJ | Ceased due to non-payment of renewal fee |