FI67548C - Foerfarande foer framstaellning av terapeutiskt anvaendbara okahydro-1h-pyrrolo(2,3-g)isokinoliner - Google Patents
Foerfarande foer framstaellning av terapeutiskt anvaendbara okahydro-1h-pyrrolo(2,3-g)isokinoliner Download PDFInfo
- Publication number
- FI67548C FI67548C FI793183A FI793183A FI67548C FI 67548 C FI67548 C FI 67548C FI 793183 A FI793183 A FI 793183A FI 793183 A FI793183 A FI 793183A FI 67548 C FI67548 C FI 67548C
- Authority
- FI
- Finland
- Prior art keywords
- alkyl
- formula
- compound
- trans
- pyrrolo
- Prior art date
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- 230000001225 therapeutic effect Effects 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims description 102
- 125000000217 alkyl group Chemical group 0.000 claims description 67
- 239000000203 mixture Substances 0.000 claims description 57
- 238000002360 preparation method Methods 0.000 claims description 29
- 239000002253 acid Substances 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 26
- 238000000034 method Methods 0.000 claims description 16
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 125000003342 alkenyl group Chemical group 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 9
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 8
- 230000003287 optical effect Effects 0.000 claims description 7
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 claims description 7
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 6
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims description 5
- 150000004820 halides Chemical class 0.000 claims description 5
- 239000002243 precursor Substances 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 239000007858 starting material Substances 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 125000001589 carboacyl group Chemical group 0.000 claims description 3
- 239000003638 chemical reducing agent Substances 0.000 claims description 3
- JRVORWMACMEOAD-UHFFFAOYSA-N [N].C1=NC=CC2=CC=CC=C21 Chemical group [N].C1=NC=CC2=CC=CC=C21 JRVORWMACMEOAD-UHFFFAOYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 1
- 125000005129 aryl carbonyl group Chemical group 0.000 claims 1
- 150000002118 epoxides Chemical class 0.000 claims 1
- 125000002541 furyl group Chemical group 0.000 claims 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 claims 1
- 229910052757 nitrogen Inorganic materials 0.000 claims 1
- 125000001544 thienyl group Chemical group 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- 238000006243 chemical reaction Methods 0.000 description 49
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 47
- 239000000243 solution Substances 0.000 description 45
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 42
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 40
- -1 e.g. Chemical group 0.000 description 40
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
- 239000007787 solid Substances 0.000 description 25
- PVKCAQKXTLCSBC-UHFFFAOYSA-N 1h-isoquinolin-4-one Chemical compound C1=CC=C2C(=O)C=NCC2=C1 PVKCAQKXTLCSBC-UHFFFAOYSA-N 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 16
- 229960000583 acetic acid Drugs 0.000 description 16
- 238000010992 reflux Methods 0.000 description 16
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000012267 brine Substances 0.000 description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 13
- 239000000908 ammonium hydroxide Substances 0.000 description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 13
- 239000000284 extract Substances 0.000 description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 12
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 12
- 238000009835 boiling Methods 0.000 description 11
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- 239000012458 free base Substances 0.000 description 10
- 239000010410 layer Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000000460 chlorine Substances 0.000 description 9
- 238000009833 condensation Methods 0.000 description 9
- 230000005494 condensation Effects 0.000 description 9
- 239000012043 crude product Substances 0.000 description 9
- 238000001704 evaporation Methods 0.000 description 9
- 230000008020 evaporation Effects 0.000 description 9
- 230000007062 hydrolysis Effects 0.000 description 9
- 238000006460 hydrolysis reaction Methods 0.000 description 9
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 8
- 125000005594 diketone group Chemical group 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- 229910021529 ammonia Inorganic materials 0.000 description 7
- 239000013256 coordination polymer Substances 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 229910052744 lithium Inorganic materials 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 5
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 5
- 229930040373 Paraformaldehyde Natural products 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 5
- 229920002866 paraformaldehyde Polymers 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 239000011701 zinc Substances 0.000 description 5
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 4
- JIHKVQUFCHKYRB-UHFFFAOYSA-N 2-methyl-1,3,4,4a,5,8a-hexahydroisoquinoline-6,8-dione Chemical compound C1C(=O)CC(=O)C2CN(C)CCC21 JIHKVQUFCHKYRB-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 241001061127 Thione Species 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- QVZMSOCLXCDORR-UHFFFAOYSA-N n-ethyl-3,5-dimethoxy-n-methylaniline;hydrochloride Chemical compound Cl.CCN(C)C1=CC(OC)=CC(OC)=C1 QVZMSOCLXCDORR-UHFFFAOYSA-N 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 235000011181 potassium carbonates Nutrition 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 229910052717 sulfur Inorganic materials 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 229910052725 zinc Inorganic materials 0.000 description 4
- ZVJBPHMCBRHVEV-XQRVVYSFSA-N (2z)-2-hydroxyiminopentan-3-one Chemical compound CCC(=O)C(\C)=N/O ZVJBPHMCBRHVEV-XQRVVYSFSA-N 0.000 description 3
- PMZDQRJGMBOQBF-UHFFFAOYSA-N 1H-quinolin-4-one Natural products C1=CC=C2C(O)=CC=NC2=C1 PMZDQRJGMBOQBF-UHFFFAOYSA-N 0.000 description 3
- JFJMWQNUCYLAQW-UHFFFAOYSA-N 2-(3,5-dimethoxycyclohexa-2,5-dien-1-yl)-n-methylethanamine Chemical compound CNCCC1C=C(OC)CC(OC)=C1 JFJMWQNUCYLAQW-UHFFFAOYSA-N 0.000 description 3
- OIPARUNOKIPYON-UHFFFAOYSA-N 3-ethyl-2-methyl-1,4a,5,6,7,8,8a,9-octahydropyrrolo[2,3-g]isoquinolin-4-one Chemical compound C1C2CCNCC2C(=O)C2=C1NC(C)=C2CC OIPARUNOKIPYON-UHFFFAOYSA-N 0.000 description 3
- DZOKENUNRMDZCS-UHFFFAOYSA-N 3h-isoquinolin-4-one Chemical compound C1=CC=C2C(=O)CN=CC2=C1 DZOKENUNRMDZCS-UHFFFAOYSA-N 0.000 description 3
- PYPHDJNEFGUASN-UHFFFAOYSA-N 3h-isoquinoline-4-thione Chemical compound C1=CC=C2C(=S)CN=CC2=C1 PYPHDJNEFGUASN-UHFFFAOYSA-N 0.000 description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 3
- 238000006027 Birch reduction reaction Methods 0.000 description 3
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 3
- 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 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- AWMVMTVKBNGEAK-UHFFFAOYSA-N Styrene oxide Chemical compound C1OC1C1=CC=CC=C1 AWMVMTVKBNGEAK-UHFFFAOYSA-N 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000002964 excitative effect Effects 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 229940093915 gynecological organic acid Drugs 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 238000006317 isomerization reaction Methods 0.000 description 3
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 3
- 239000012452 mother liquor Substances 0.000 description 3
- VGPBPWRBXBKGRE-UHFFFAOYSA-N n-(oxomethylidene)hydroxylamine Chemical compound ON=C=O VGPBPWRBXBKGRE-UHFFFAOYSA-N 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 235000005985 organic acids Nutrition 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- VSGPVHSTVTXREH-UHFFFAOYSA-N quinolin-4-one Chemical compound C1=CC=C[C]2C(=O)C=CN=C21 VSGPVHSTVTXREH-UHFFFAOYSA-N 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 230000003595 spectral effect Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- VJFARDWQCMLCGT-UHFFFAOYSA-N 1,2,3,4,4a,5-hexahydroisoquinoline Chemical compound C1C=CC=C2CNCCC21 VJFARDWQCMLCGT-UHFFFAOYSA-N 0.000 description 2
- BGJSXRVXTHVRSN-UHFFFAOYSA-N 1,3,5-trioxane Chemical compound C1OCOCO1 BGJSXRVXTHVRSN-UHFFFAOYSA-N 0.000 description 2
- ORCJWYKSNVSPRX-UHFFFAOYSA-N 1,4a,5,6,7,8,8a,9-octahydropyrrolo[2,3-g]isoquinolin-4-one Chemical compound O=C1C2CNCCC2CC2=C1C=CN2 ORCJWYKSNVSPRX-UHFFFAOYSA-N 0.000 description 2
- QKWWDTYDYOFRJL-UHFFFAOYSA-N 2,2-dimethoxyethanamine Chemical compound COC(CN)OC QKWWDTYDYOFRJL-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- PVZMYDPRVUCJKV-UHFFFAOYSA-N 3-ethyl-2,6-dimethyl-4a,5,7,8,8a,9-hexahydro-1h-pyrrolo[2,3-g]isoquinolin-4-one Chemical compound C1C2CCN(C)CC2C(=O)C2=C1NC(C)=C2CC PVZMYDPRVUCJKV-UHFFFAOYSA-N 0.000 description 2
- GDPDIPLTWCMPIC-UHFFFAOYSA-N 3-ethyl-2-methyl-1,4a,5,6,7,8,8a,9-octahydropyrrolo[2,3-g]isoquinoline-4-thione Chemical compound C1C2CCNCC2C(=S)C2=C1NC(C)=C2CC GDPDIPLTWCMPIC-UHFFFAOYSA-N 0.000 description 2
- UEGVVERPSDYMKW-UHFFFAOYSA-N 4h-pyrrolo[2,3-g]isoquinoline Chemical class C1=NC=C2CC3=CC=NC3=CC2=C1 UEGVVERPSDYMKW-UHFFFAOYSA-N 0.000 description 2
- JYRADYLOSIMJFK-UHFFFAOYSA-N 6,8-dimethoxy-2-methyl-3,4,4a,7-tetrahydro-1h-isoquinoline Chemical compound C1CN(C)CC2=C(OC)CC(OC)=CC21 JYRADYLOSIMJFK-UHFFFAOYSA-N 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- 101100178313 Aedes aegypti HP-I gene Proteins 0.000 description 2
- 241000234282 Allium Species 0.000 description 2
- 235000002732 Allium cepa var. cepa Nutrition 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- PKXADSMBZJCAGK-UHFFFAOYSA-N Cl.C1=CC=C2C(=O)CN=CC2=C1 Chemical compound Cl.C1=CC=C2C(=O)CN=CC2=C1 PKXADSMBZJCAGK-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 101710094396 Hexon protein Proteins 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 238000006683 Mannich reaction Methods 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 238000006900 dealkylation reaction Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
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- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- IWOKCMBOJXYDEE-UHFFFAOYSA-N sulfinylmethane Chemical compound C=S=O IWOKCMBOJXYDEE-UHFFFAOYSA-N 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-O sulfonium Chemical compound [SH3+] RWSOTUBLDIXVET-UHFFFAOYSA-O 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 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 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000004809 thin layer chromatography Methods 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
- JREYOWJEWZVAOR-UHFFFAOYSA-N triazanium;[3-methylbut-3-enoxy(oxido)phosphoryl] phosphate Chemical compound [NH4+].[NH4+].[NH4+].CC(=C)CCOP([O-])(=O)OP([O-])([O-])=O JREYOWJEWZVAOR-UHFFFAOYSA-N 0.000 description 1
- 150000003673 urethanes Chemical class 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 239000004246 zinc acetate Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/04—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
-
- 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
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Psychiatry (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurosurgery (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI801159A FI68833C (fi) | 1979-10-12 | 1980-04-11 | Foerfarande foer framstaellning av terapeutiskt anvaendbara cyloalka(4,5)pyrrolo(2,3-g)isokinoliner |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US95094778A | 1978-10-13 | 1978-10-13 | |
| US95094778 | 1978-10-13 | ||
| US06/073,813 US4260762A (en) | 1979-09-10 | 1979-09-10 | Octahydro-1H-pyrrolo[2,3-g]isoquinolines |
| US7381379 | 1979-09-10 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI793183A7 FI793183A7 (fi) | 1980-04-14 |
| FI67548B FI67548B (fi) | 1984-12-31 |
| FI67548C true FI67548C (fi) | 1985-04-10 |
Family
ID=26754910
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI793183A FI67548C (fi) | 1978-10-13 | 1979-10-12 | Foerfarande foer framstaellning av terapeutiskt anvaendbara okahydro-1h-pyrrolo(2,3-g)isokinoliner |
Country Status (18)
| Country | Link |
|---|---|
| EP (1) | EP0010661B1 (cs) |
| AR (2) | AR228244A1 (cs) |
| AU (1) | AU528685B2 (cs) |
| CA (1) | CA1132553A (cs) |
| CS (1) | CS242858B2 (cs) |
| DE (1) | DE2967215D1 (cs) |
| DK (1) | DK430579A (cs) |
| ES (2) | ES493015A0 (cs) |
| FI (1) | FI67548C (cs) |
| HU (1) | HU181883B (cs) |
| IE (1) | IE48965B1 (cs) |
| IL (1) | IL58438A (cs) |
| MC (1) | MC1285A1 (cs) |
| NO (1) | NO152873C (cs) |
| NZ (1) | NZ191830A (cs) |
| PH (1) | PH14835A (cs) |
| PT (1) | PT70310A (cs) |
| SU (3) | SU1109052A3 (cs) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MC1377A1 (fr) * | 1980-02-28 | 1982-01-19 | Hoffmann La Roche | Derives d'isoquinoleine |
| DE3363146D1 (en) * | 1982-03-29 | 1986-05-28 | Hoffmann La Roche | Process for the manufacture of isoquinoline diones |
| US4732902A (en) * | 1986-05-23 | 1988-03-22 | Hoffmann-La Roche Inc. | Pyrroloisoquinolinyl-dimethyloxoalkyl alkonoates and their use as antipsychotic agents |
| GB8828669D0 (en) * | 1988-12-08 | 1989-01-11 | Lilly Industries Ltd | Organic compounds |
| US6344589B1 (en) | 1998-11-20 | 2002-02-05 | Basf Aktiengesellschaft | Method and intermediate products for producing bis(oxime)monoethers |
-
1979
- 1979-09-27 CA CA336,495A patent/CA1132553A/en not_active Expired
- 1979-10-08 SU SU792819251A patent/SU1109052A3/ru active
- 1979-10-08 SU SU812819251K patent/SU1014474A3/ru active
- 1979-10-10 MC MC791409A patent/MC1285A1/xx unknown
- 1979-10-11 EP EP79103908A patent/EP0010661B1/de not_active Expired
- 1979-10-11 DE DE7979103908T patent/DE2967215D1/de not_active Expired
- 1979-10-11 NZ NZ191830A patent/NZ191830A/en unknown
- 1979-10-11 IL IL58438A patent/IL58438A/xx unknown
- 1979-10-11 AU AU51697/79A patent/AU528685B2/en not_active Ceased
- 1979-10-11 DK DK430579A patent/DK430579A/da not_active Application Discontinuation
- 1979-10-12 FI FI793183A patent/FI67548C/fi not_active IP Right Cessation
- 1979-10-12 PT PT70310A patent/PT70310A/pt unknown
- 1979-10-12 HU HU79HO2188A patent/HU181883B/hu not_active IP Right Cessation
- 1979-10-12 CS CS796945A patent/CS242858B2/cs unknown
- 1979-10-12 PH PH23160A patent/PH14835A/en unknown
- 1979-10-12 IE IE1944/79A patent/IE48965B1/en unknown
- 1979-10-12 AR AR278488A patent/AR228244A1/es active
- 1979-10-12 NO NO793301A patent/NO152873C/no unknown
-
1980
- 1980-07-02 ES ES493015A patent/ES493015A0/es active Granted
- 1980-07-02 ES ES493014A patent/ES493014A0/es active Granted
-
1981
- 1981-03-02 SU SU813250198A patent/SU1048985A3/ru active
- 1981-07-02 AR AR285961A patent/AR229096A1/es active
Also Published As
| Publication number | Publication date |
|---|---|
| AU5169779A (en) | 1980-04-17 |
| AU528685B2 (en) | 1983-05-12 |
| IE48965B1 (en) | 1985-06-26 |
| ES8104805A1 (es) | 1981-05-16 |
| HU181883B (en) | 1983-11-28 |
| DK430579A (da) | 1980-04-14 |
| SU1109052A3 (ru) | 1984-08-15 |
| EP0010661A2 (de) | 1980-05-14 |
| CA1132553A (en) | 1982-09-28 |
| IL58438A (en) | 1982-12-31 |
| EP0010661A3 (en) | 1980-10-01 |
| NO793301L (no) | 1980-04-15 |
| ES493014A0 (es) | 1981-05-16 |
| AR229096A1 (es) | 1983-06-15 |
| SU1048985A3 (ru) | 1983-10-15 |
| MC1285A1 (fr) | 1980-07-22 |
| NO152873B (no) | 1985-08-26 |
| ES8104806A1 (es) | 1981-05-16 |
| IE791944L (en) | 1980-04-13 |
| NZ191830A (en) | 1984-09-28 |
| SU1014474A3 (ru) | 1983-04-23 |
| FI67548B (fi) | 1984-12-31 |
| PH14835A (en) | 1981-12-16 |
| FI793183A7 (fi) | 1980-04-14 |
| NO152873C (no) | 1985-12-04 |
| CS242858B2 (en) | 1986-05-15 |
| IL58438A0 (en) | 1980-01-31 |
| EP0010661B1 (de) | 1984-09-12 |
| AR228244A1 (es) | 1983-02-15 |
| PT70310A (en) | 1979-11-01 |
| CS694579A2 (en) | 1985-08-15 |
| DE2967215D1 (en) | 1984-10-18 |
| ES493015A0 (es) | 1981-05-16 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: F HOFFMANN-LA ROCHE & CO |