DE69311165T2 - Kondensierte heterocyclische Ketonderivate, ihre Herstellung und ihre Verwendung - Google Patents
Kondensierte heterocyclische Ketonderivate, ihre Herstellung und ihre VerwendungInfo
- Publication number
- DE69311165T2 DE69311165T2 DE69311165T DE69311165T DE69311165T2 DE 69311165 T2 DE69311165 T2 DE 69311165T2 DE 69311165 T DE69311165 T DE 69311165T DE 69311165 T DE69311165 T DE 69311165T DE 69311165 T2 DE69311165 T2 DE 69311165T2
- Authority
- DE
- Germany
- Prior art keywords
- group
- substituted
- alkyl
- mono
- amino
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- -1 heterocyclic ketone Chemical class 0.000 title claims description 377
- 238000002360 preparation method Methods 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 243
- 150000003839 salts Chemical class 0.000 claims abstract description 117
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 46
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 35
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 34
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 18
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 15
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 15
- 206010039966 Senile dementia Diseases 0.000 claims abstract description 14
- 102000003914 Cholinesterases Human genes 0.000 claims abstract description 12
- 108090000322 Cholinesterases Proteins 0.000 claims abstract description 12
- 229940048961 cholinesterase Drugs 0.000 claims abstract description 12
- 125000001424 substituent group Chemical group 0.000 claims description 71
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 54
- 229910052736 halogen Inorganic materials 0.000 claims description 48
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 46
- 125000005843 halogen group Chemical group 0.000 claims description 44
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 40
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 35
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 33
- 150000002367 halogens Chemical class 0.000 claims description 31
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 30
- 125000000217 alkyl group Chemical group 0.000 claims description 29
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 27
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 25
- 125000003236 benzoyl group Chemical class [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 24
- 229910052717 sulfur Inorganic materials 0.000 claims description 21
- 125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 claims description 20
- 125000004739 (C1-C6) alkylsulfonyl group Chemical class 0.000 claims description 20
- 125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 claims description 20
- 229910052760 oxygen Inorganic materials 0.000 claims description 20
- 125000005842 heteroatom Chemical group 0.000 claims description 16
- 125000003277 amino group Chemical group 0.000 claims description 15
- 125000001624 naphthyl group Chemical group 0.000 claims description 15
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 13
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 12
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 12
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 12
- 230000000694 effects Effects 0.000 claims description 11
- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 125000002541 furyl group Chemical group 0.000 claims description 9
- 125000004414 alkyl thio group Chemical group 0.000 claims description 8
- 239000000544 cholinesterase inhibitor Substances 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 8
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 7
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 7
- 125000002757 morpholinyl group Chemical group 0.000 claims description 7
- 125000004043 oxo group Chemical group O=* 0.000 claims description 7
- 125000006678 phenoxycarbonyl group Chemical group 0.000 claims description 7
- 125000004193 piperazinyl group Chemical group 0.000 claims description 7
- 125000003386 piperidinyl group Chemical group 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 6
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000004122 cyclic group Chemical group 0.000 claims description 6
- 125000002950 monocyclic group Chemical group 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 5
- 125000005947 C1-C6 alkylsulfonyloxy group Chemical group 0.000 claims description 4
- 229940122041 Cholinesterase inhibitor Drugs 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000005974 C6-C14 arylcarbonyl group Chemical group 0.000 claims description 3
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 3
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 3
- 125000005400 pyridylcarbonyl group Chemical group N1=C(C=CC=C1)C(=O)* 0.000 claims description 3
- 125000004434 sulfur atom Chemical group 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 239000004305 biphenyl Substances 0.000 claims description 2
- 235000010290 biphenyl Nutrition 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 2
- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 53
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 4
- 102100033639 Acetylcholinesterase Human genes 0.000 claims 2
- 108010022752 Acetylcholinesterase Proteins 0.000 claims 2
- 229940022698 acetylcholinesterase Drugs 0.000 claims 2
- 125000005530 alkylenedioxy group Chemical group 0.000 claims 2
- 125000004191 (C1-C6) alkoxy group Chemical class 0.000 claims 1
- SBGOLVMITIRYPS-UHFFFAOYSA-N 1-(1-benzyl-2,3-dihydroindol-5-yl)-3-(4-benzylpiperazin-1-yl)propan-1-one Chemical compound C=1C=C2N(CC=3C=CC=CC=3)CCC2=CC=1C(=O)CCN(CC1)CCN1CC1=CC=CC=C1 SBGOLVMITIRYPS-UHFFFAOYSA-N 0.000 claims 1
- FVTFVCGFZLWINH-UHFFFAOYSA-N 3-(4-benzylpiperazin-1-yl)-1-(2-benzyl-1,3,4,5-tetrahydro-2-benzazepin-8-yl)propan-1-one Chemical compound C=1C=C2CCCN(CC=3C=CC=CC=3)CC2=CC=1C(=O)CCN(CC1)CCN1CC1=CC=CC=C1 FVTFVCGFZLWINH-UHFFFAOYSA-N 0.000 claims 1
- VUHUXGACMWJCPL-UHFFFAOYSA-N 3-(4-benzylpiperazin-1-yl)-1-(3-benzyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)propan-1-one Chemical compound C=1C=C2CCN(CC=3C=CC=CC=3)CCC2=CC=1C(=O)CCN(CC1)CCN1CC1=CC=CC=C1 VUHUXGACMWJCPL-UHFFFAOYSA-N 0.000 claims 1
- ZZMLXTXUXITSNI-UHFFFAOYSA-N 3-(4-benzylpiperazin-1-yl)-1-[3-(2-methylpropyl)-1,2,4,5-tetrahydro-3-benzazepin-7-yl]propan-1-one Chemical compound C1=C2CCN(CC(C)C)CCC2=CC=C1C(=O)CCN(CC1)CCN1CC1=CC=CC=C1 ZZMLXTXUXITSNI-UHFFFAOYSA-N 0.000 claims 1
- WDZHNTDCWRKWOW-UHFFFAOYSA-N 3-(4-benzylpiperazin-1-yl)-1-[3-(2-phenylethyl)-1,2,4,5-tetrahydro-3-benzazepin-7-yl]propan-1-one Chemical compound C=1C=C2CCN(CCC=3C=CC=CC=3)CCC2=CC=1C(=O)CCN(CC1)CCN1CC1=CC=CC=C1 WDZHNTDCWRKWOW-UHFFFAOYSA-N 0.000 claims 1
- QNQXUZDRKXZTBM-UHFFFAOYSA-N 3-(4-benzylpiperazin-1-yl)-1-[3-[(4-methoxyphenyl)methyl]-1,2,4,5-tetrahydro-3-benzazepin-7-yl]propan-1-one Chemical compound C1=CC(OC)=CC=C1CN1CCC2=CC(C(=O)CCN3CCN(CC=4C=CC=CC=4)CC3)=CC=C2CC1 QNQXUZDRKXZTBM-UHFFFAOYSA-N 0.000 claims 1
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims 1
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- 239000004615 ingredient Substances 0.000 claims 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
- 150000002430 hydrocarbons Chemical class 0.000 abstract description 31
- 125000002252 acyl group Chemical class 0.000 abstract description 15
- 230000001225 therapeutic effect Effects 0.000 abstract description 11
- 230000000069 prophylactic effect Effects 0.000 abstract description 10
- 229930195733 hydrocarbon Natural products 0.000 abstract description 8
- 239000004215 Carbon black (E152) Substances 0.000 abstract description 7
- 230000000407 monoamine reuptake Effects 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 3
- 230000001747 exhibiting effect Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 75
- 239000002904 solvent Substances 0.000 description 59
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 53
- 239000000203 mixture Substances 0.000 description 36
- 239000000243 solution Substances 0.000 description 35
- 238000000034 method Methods 0.000 description 34
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 28
- 239000000460 chlorine Substances 0.000 description 23
- 229910052801 chlorine Inorganic materials 0.000 description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 20
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 19
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 19
- 229910052794 bromium Inorganic materials 0.000 description 19
- 238000000921 elemental analysis Methods 0.000 description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- 239000013078 crystal Substances 0.000 description 17
- 229910052731 fluorine Inorganic materials 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 16
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 16
- 239000011737 fluorine Substances 0.000 description 16
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 15
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
- 238000000605 extraction Methods 0.000 description 14
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 12
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 230000008569 process Effects 0.000 description 12
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 12
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 10
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 10
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 10
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 10
- 239000000843 powder Substances 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 9
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 9
- 229920002261 Corn starch Polymers 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 239000008120 corn starch Substances 0.000 description 8
- 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 8
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 125000004344 phenylpropyl group Chemical group 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 7
- 239000012458 free base Substances 0.000 description 7
- 235000011087 fumaric acid Nutrition 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 7
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 125000003545 alkoxy group Chemical group 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 239000001530 fumaric acid Substances 0.000 description 6
- 150000007529 inorganic bases Chemical class 0.000 description 6
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 6
- 150000007522 mineralic acids Chemical class 0.000 description 6
- 150000007530 organic bases Chemical class 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-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
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 5
- 239000005711 Benzoic acid Substances 0.000 description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 5
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 5
- 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 5
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 5
- PIJVFDBKTWXHHD-UHFFFAOYSA-N Physostigmine Natural products C12=CC(OC(=O)NC)=CC=C2N(C)C2C1(C)CCN2C PIJVFDBKTWXHHD-UHFFFAOYSA-N 0.000 description 5
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 5
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 5
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 5
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 5
- 235000011054 acetic acid Nutrition 0.000 description 5
- 229910052783 alkali metal Inorganic materials 0.000 description 5
- 150000001340 alkali metals Chemical class 0.000 description 5
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 5
- 150000001342 alkaline earth metals Chemical class 0.000 description 5
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 5
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 5
- 229910021529 ammonia Inorganic materials 0.000 description 5
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 5
- 229940092714 benzenesulfonic acid Drugs 0.000 description 5
- 235000010233 benzoic acid Nutrition 0.000 description 5
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 5
- 239000011575 calcium Substances 0.000 description 5
- 229910052791 calcium Inorganic materials 0.000 description 5
- 235000015165 citric acid Nutrition 0.000 description 5
- 125000000753 cycloalkyl group Chemical group 0.000 description 5
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 5
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- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical class C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 229940043274 prophylactic drug Drugs 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000005412 pyrazyl group Chemical group 0.000 description 1
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 1
- CYIDZMCFTVVTJO-UHFFFAOYSA-N pyromellityc acid Natural products OC(=O)C1=CC(C(O)=O)=C(C(O)=O)C=C1C(O)=O CYIDZMCFTVVTJO-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 150000008515 quinazolinediones Chemical class 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 208000026451 salivation Diseases 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000005504 styryl group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 210000002820 sympathetic nervous system Anatomy 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 125000004933 β-carbolinyl group Chemical group C1(=NC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
Classifications
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/04—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
- C07D215/08—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms with acylated ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D225/00—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom
- C07D225/04—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D225/06—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems condensed with one six-membered ring
-
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D401/02—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
- C07D401/12—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 chain containing hetero atoms as chain links
-
- 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
- C07D405/02—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 two hetero rings
- C07D405/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed systems
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/582—Recycling of unreacted starting or intermediate materials
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pyridine Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP5096092 | 1992-03-09 | ||
JP9794892 | 1992-04-17 | ||
JP14585292 | 1992-06-05 | ||
JP21022592 | 1992-08-06 | ||
JP25960692 | 1992-09-29 |
Publications (2)
Publication Number | Publication Date |
---|---|
DE69311165D1 DE69311165D1 (de) | 1997-07-10 |
DE69311165T2 true DE69311165T2 (de) | 1997-09-18 |
Family
ID=27522916
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE69311165T Expired - Fee Related DE69311165T2 (de) | 1992-03-09 | 1993-03-06 | Kondensierte heterocyclische Ketonderivate, ihre Herstellung und ihre Verwendung |
Country Status (11)
Families Citing this family (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5639748A (en) * | 1991-08-05 | 1997-06-17 | Smithkline Beecham Corporation | 6,9-disubstituted benzazepines having α-adrenoceptor blocking activity |
US5620973A (en) * | 1993-11-30 | 1997-04-15 | Takeda Chemical Industries, Ltd. | Tetracyclic condensed heterocyclic compounds and their use |
US5658909A (en) * | 1994-11-17 | 1997-08-19 | Molecular Geriatrics Corporation | Certain substituted 1-aryl-3-piperazin-1'-yl propanones to treat Alzheimer's Disease |
US5705501A (en) * | 1994-11-17 | 1998-01-06 | Molecular Geriatrics Corporation | Certain substituted 1-aryl-3-morpholinopropanones to treat Alzheimer's Disease |
GB2308362A (en) * | 1995-12-19 | 1997-06-25 | Lilly Industries Ltd | Pharmaceutical indole derivatives |
AU6852898A (en) * | 1997-04-17 | 1998-11-11 | Takeda Chemical Industries Ltd. | Thermogenic composition and benzazepine thermogenics |
US6500820B1 (en) | 1998-04-23 | 2002-12-31 | Takeda Chemical Industries, Ltd. | Pharmaceutical composition for neurotrophic action |
EP1891954A3 (en) | 1998-09-30 | 2009-01-14 | Takeda Pharmaceutical Company Limited | Acetylcholinesterase inhibitors for improving excretory potency of urinary bladder |
CA2408913A1 (en) * | 2000-05-16 | 2001-11-22 | Takeda Chemical Industries, Ltd. | Melanin-concentrating hormone antagonist |
CA2414976A1 (en) * | 2000-07-04 | 2002-01-10 | Takeda Chemical Industries, Ltd. | Gpr14 antagonistic agent |
WO2002014513A1 (en) * | 2000-08-10 | 2002-02-21 | Takeda Chemical Industries, Ltd. | Use of polypeptide |
BR0215389A (pt) | 2001-12-28 | 2004-10-26 | Takeda Chemical Industries Ltd | Agente preventivo ou terapêutico para distúrbio urinário, método para prevenir ou tratar distúrbio urinário, uso de um composto, composto, pró-droga, processo para preparar o composto, medicamento, e, método para triar um composto |
GB201106817D0 (en) | 2011-04-21 | 2011-06-01 | Astex Therapeutics Ltd | New compound |
GB201218862D0 (en) | 2012-10-19 | 2012-12-05 | Astex Therapeutics Ltd | Bicyclic heterocycle compounds and their uses in therapy |
GB201218864D0 (en) | 2012-10-19 | 2012-12-05 | Astex Therapeutics Ltd | Bicyclic heterocycle compounds and their uses in therapy |
GB201218850D0 (en) | 2012-10-19 | 2012-12-05 | Astex Therapeutics Ltd | Bicyclic heterocycle compounds and their uses in therapy |
US9980973B2 (en) | 2012-10-19 | 2018-05-29 | Astex Therapeutics Limited | Bicyclic heterocycle compounds and their uses in therapy |
CN109336883B (zh) | 2013-12-20 | 2022-06-14 | 阿斯特克斯治疗有限公司 | 双环杂环化合物及其治疗用途 |
CN115433116B (zh) * | 2022-09-20 | 2023-07-14 | 徐州医科大学 | 一种酰化吲哚啉类衍生物、组合物及其应用 |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FI73423C (fi) * | 1980-02-29 | 1987-10-09 | Otsuka Pharma Co Ltd | Foerfarande foer framstaellning av farmakologiskt verksamma tetrazolderivat. |
US4521606A (en) * | 1983-06-30 | 1985-06-04 | American Home Products Corp. | 5-Indolyl substituted aminoethanols |
DK623586A (da) * | 1985-12-27 | 1987-06-28 | Eisai Co Ltd | Piperidinderivater eller salte deraf og farmaceutiske kompositioner indeholdende forbindelserne |
AU614965B2 (en) * | 1987-06-06 | 1991-09-19 | Merck Patent Gesellschaft Mit Beschrankter Haftung | Thiadiazinones |
JP2699511B2 (ja) * | 1988-01-29 | 1998-01-19 | 武田薬品工業株式会社 | 置換アミン類 |
FR2640266B2 (fr) * | 1988-07-12 | 1992-07-10 | Synthelabo | Derives de (hydroxy-1 piperidinyl-2 alkyl) indolones-2, quinoleinones-2, benzo(b)azepinones-2 et benzimidazolones-2, leur preparation et leur application en therapeutique |
TW197435B (US07229986-20070612-C00042.png) * | 1990-11-22 | 1993-01-01 | Takeda Pharm Industry Co Ltd |
-
1993
- 1993-02-16 TW TW082101055A patent/TW218875B/zh active
- 1993-02-23 NZ NZ245974A patent/NZ245974A/en unknown
- 1993-03-03 NO NO93930783A patent/NO930783L/no unknown
- 1993-03-05 MX MX9301240A patent/MX9301240A/es unknown
- 1993-03-06 AT AT93103614T patent/ATE154020T1/de not_active IP Right Cessation
- 1993-03-06 EP EP93103614A patent/EP0560235B1/en not_active Expired - Lifetime
- 1993-03-06 DE DE69311165T patent/DE69311165T2/de not_active Expired - Fee Related
- 1993-03-08 FI FI931011A patent/FI931011A/fi not_active Application Discontinuation
- 1993-03-08 CA CA002091216A patent/CA2091216A1/en not_active Abandoned
- 1993-03-09 HU HU9300659A patent/HUT67283A/hu unknown
- 1993-03-09 CN CN93102438A patent/CN1039119C/zh not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
ATE154020T1 (de) | 1997-06-15 |
DE69311165D1 (de) | 1997-07-10 |
NO930783D0 (no) | 1993-03-03 |
CA2091216A1 (en) | 1993-09-10 |
EP0560235A1 (en) | 1993-09-15 |
HUT67283A (en) | 1995-03-28 |
NZ245974A (en) | 1995-04-27 |
CN1078969A (zh) | 1993-12-01 |
FI931011A0 (fi) | 1993-03-08 |
FI931011A (fi) | 1993-09-10 |
TW218875B (US07229986-20070612-C00042.png) | 1994-01-11 |
HU9300659D0 (en) | 1993-05-28 |
EP0560235B1 (en) | 1997-06-04 |
MX9301240A (es) | 1993-12-01 |
CN1039119C (zh) | 1998-07-15 |
NO930783L (no) | 1993-09-10 |
AU3380393A (en) | 1993-09-16 |
AU658481B2 (en) | 1995-04-13 |
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Owner name: TAKEDA PHARMACEUTICAL CO. LTD., OSAKA, JP |
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8339 | Ceased/non-payment of the annual fee |