NO862120L - Fremgangsmaate ved fremstilling av terapeutisk aktive isokinolinderivater. - Google Patents
Fremgangsmaate ved fremstilling av terapeutisk aktive isokinolinderivater.Info
- Publication number
- NO862120L NO862120L NO862120A NO862120A NO862120L NO 862120 L NO862120 L NO 862120L NO 862120 A NO862120 A NO 862120A NO 862120 A NO862120 A NO 862120A NO 862120 L NO862120 L NO 862120L
- Authority
- NO
- Norway
- Prior art keywords
- group
- hydrogen atom
- formula
- compound
- methyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 20
- 238000002360 preparation method Methods 0.000 title claims description 12
- 230000001225 therapeutic effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 86
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 44
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 32
- 150000003839 salts Chemical class 0.000 claims description 22
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
- 239000000203 mixture Substances 0.000 claims description 19
- -1 methylenedioxy group Chemical group 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 3
- 125000004423 acyloxy group Chemical group 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 125000004434 sulfur atom Chemical group 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 125000006413 ring segment Chemical group 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 4
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims 1
- 150000008065 acid anhydrides Chemical class 0.000 claims 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 51
- 239000000543 intermediate Substances 0.000 description 30
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 150000002148 esters Chemical class 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- 206010028980 Neoplasm Diseases 0.000 description 11
- 238000001914 filtration Methods 0.000 description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- SGXDXUYKISDCAZ-UHFFFAOYSA-N N,N-diethylglycine Chemical compound CCN(CC)CC(O)=O SGXDXUYKISDCAZ-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- 238000003776 cleavage reaction Methods 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 230000007017 scission Effects 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 238000002425 crystallisation Methods 0.000 description 6
- 230000008025 crystallization Effects 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 125000001309 chloro group Chemical group Cl* 0.000 description 5
- PNVPNXKRAUBJGW-UHFFFAOYSA-N (2-chloroacetyl) 2-chloroacetate Chemical compound ClCC(=O)OC(=O)CCl PNVPNXKRAUBJGW-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 4
- 239000013067 intermediate product Substances 0.000 description 4
- JDNTWHVOXJZDSN-UHFFFAOYSA-N iodoacetic acid Chemical compound OC(=O)CI JDNTWHVOXJZDSN-UHFFFAOYSA-N 0.000 description 4
- KQPYUDDGWXQXHS-UHFFFAOYSA-N juglone Chemical compound O=C1C=CC(=O)C2=C1C=CC=C2O KQPYUDDGWXQXHS-UHFFFAOYSA-N 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000001093 anti-cancer Effects 0.000 description 3
- 150000003840 hydrochlorides Chemical class 0.000 description 3
- 125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 2
- KSRBEBKFXYLKHC-UHFFFAOYSA-N 2-(dipropylazaniumyl)acetate Chemical compound CCCN(CCC)CC(O)=O KSRBEBKFXYLKHC-UHFFFAOYSA-N 0.000 description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 101150041968 CDC13 gene Proteins 0.000 description 2
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 2
- FFDGPVCHZBVARC-UHFFFAOYSA-N N,N-dimethylglycine Chemical compound CN(C)CC(O)=O FFDGPVCHZBVARC-UHFFFAOYSA-N 0.000 description 2
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 2
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- RQNVIKXOOKXAJQ-UHFFFAOYSA-N naphthazarin Chemical compound O=C1C=CC(=O)C2=C1C(O)=CC=C2O RQNVIKXOOKXAJQ-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 235000009518 sodium iodide Nutrition 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- HKYIQARCILRMSR-UHFFFAOYSA-N (3-methyl-14,21-dioxo-11-azapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1,4,6,8,12,15(20),16,18-octaen-16-yl) 2-(diethylamino)acetate Chemical compound CC1C=2N(CC3=CC=CC=C13)C=C1C(C3=C(C(C12)=O)C=CC=C3OC(CN(CC)CC)=O)=O HKYIQARCILRMSR-UHFFFAOYSA-N 0.000 description 1
- TXFIESXQCDPOLR-UHFFFAOYSA-N (5,8-dichloro-1,4-dioxonaphthalen-2-yl) acetate Chemical compound C1=CC(Cl)=C2C(=O)C(OC(=O)C)=CC(=O)C2=C1Cl TXFIESXQCDPOLR-UHFFFAOYSA-N 0.000 description 1
- HYJHZCJYZCQUGN-UHFFFAOYSA-N (5,8-dioxonaphthalen-1-yl) 2-iodoacetate Chemical compound O=C1C=CC(=O)C2=C1C=CC=C2OC(=O)CI HYJHZCJYZCQUGN-UHFFFAOYSA-N 0.000 description 1
- MHRNGQVWZRPUJI-UHFFFAOYSA-N 2-formyl-3,4-dihydro-1h-isoquinoline-3-carboxylic acid Chemical compound C1=CC=C2CN(C=O)C(C(=O)O)CC2=C1 MHRNGQVWZRPUJI-UHFFFAOYSA-N 0.000 description 1
- 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 1
- YMTCJQDWNOXXMO-UHFFFAOYSA-N 4-methyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid Chemical compound C1=CC=C2C(C)C(C(O)=O)NCC2=C1 YMTCJQDWNOXXMO-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
- 235000013162 Cocos nucifera Nutrition 0.000 description 1
- 244000060011 Cocos nucifera Species 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 1
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- HARNYOXPRCQLTD-UHFFFAOYSA-N acetyl 2-formyl-4-methyl-3,4,4a,5-tetrahydro-1H-isoquinoline-3-carboxylate Chemical compound C(C)(=O)OC(=O)C1N(CC2=CC=CCC2C1C)C=O HARNYOXPRCQLTD-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
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- VYTBDSUNRJYVHL-UHFFFAOYSA-N beta-Hydrojuglone Natural products O=C1CCC(=O)C2=C1C=CC=C2O VYTBDSUNRJYVHL-UHFFFAOYSA-N 0.000 description 1
- CLZTVBHOOQTDNP-UHFFFAOYSA-N butanoic acid;dichloromethane Chemical compound ClCCl.CCCC(O)=O CLZTVBHOOQTDNP-UHFFFAOYSA-N 0.000 description 1
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- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
- 229940106681 chloroacetic acid Drugs 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical compound CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
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- 239000012153 distilled water Substances 0.000 description 1
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- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
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- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
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- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- XHFXMNZYIKFCPN-UHFFFAOYSA-N perchloryl fluoride Chemical compound FCl(=O)(=O)=O XHFXMNZYIKFCPN-UHFFFAOYSA-N 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Chemical compound OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
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- 150000004053 quinones Chemical class 0.000 description 1
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- 239000008107 starch Substances 0.000 description 1
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- 239000001334 starch sodium octenyl succinate Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
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- 150000003890 succinate salts Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
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- 150000003892 tartrate salts Chemical class 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 125000005505 thiomorpholino group Chemical group 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07D491/12—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 three hetero rings
- C07D491/14—Ortho-condensed systems
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO893751A NO166001C (no) | 1985-05-29 | 1989-09-20 | Isokinolinderivater. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB858513460A GB8513460D0 (en) | 1985-05-29 | 1985-05-29 | Chemical compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO862120L true NO862120L (no) | 1986-12-01 |
Family
ID=10579796
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO862120A NO862120L (no) | 1985-05-29 | 1986-05-28 | Fremgangsmaate ved fremstilling av terapeutisk aktive isokinolinderivater. |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US4900737A (fr) |
| JP (1) | JPS6212778A (fr) |
| KR (1) | KR860009015A (fr) |
| BE (1) | BE904835A (fr) |
| CH (2) | CH668596A5 (fr) |
| DE (1) | DE3617938A1 (fr) |
| DK (1) | DK246986A (fr) |
| ES (2) | ES8800942A1 (fr) |
| FI (1) | FI862277A (fr) |
| FR (1) | FR2584072B1 (fr) |
| GB (2) | GB8513460D0 (fr) |
| IT (1) | IT1191931B (fr) |
| NL (1) | NL8601381A (fr) |
| NO (1) | NO862120L (fr) |
| NZ (1) | NZ216338A (fr) |
| PH (2) | PH24002A (fr) |
| SE (2) | SE8602434L (fr) |
| ZA (1) | ZA864015B (fr) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK616087A (da) * | 1986-11-27 | 1988-05-28 | Glaxo Group Ltd | Isoquinolinderivater og farmaceutiske praeparater indeholdende dem |
| GB8800312D0 (en) * | 1988-01-07 | 1988-02-10 | Glaxo Group Ltd | Process |
| FR2801309B1 (fr) * | 1999-11-18 | 2002-01-04 | Adir | Nouveaux composes analogues de la camptothecine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| CN114805204B (zh) * | 2022-04-01 | 2023-09-15 | 云南师范大学 | 一种制备4-碘异喹啉-1(2h)-酮类化合物的方法 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4029659A (en) * | 1971-03-29 | 1977-06-14 | Omnium Chimique Societe Anonyme | N-disubstituted aminoethyl esters of 11-methoxy-raubasinic acid |
| US3894029A (en) * | 1971-08-26 | 1975-07-08 | Basf Ag | Production of camptothecin and camptothecin-like compounds |
| US3903276A (en) * | 1972-03-20 | 1975-09-02 | American Home Prod | N-carboxymethyl-N-substituted glycinate esters of 3-hydroxy-1,4-benzodiazepin-2-ones for inducing a calming effect |
| US4301285A (en) * | 1980-10-02 | 1981-11-17 | American Home Products Corporation | Sydnonimine CNS stimulants |
| NL8202626A (nl) * | 1982-06-29 | 1984-01-16 | Stichting Rega V Z W | Derivaten van 9-(2-hydroxyethoxymethyl)guanine. |
| DK158666C (da) * | 1982-11-04 | 1990-11-19 | Glaxo Group Ltd | Analogifremgangsmaade til fremstilling af 5,14-dihydrobenz-oe5,6aa-isoindolooe2,1-baa-isoquinolin-8,13-dion |
| DE3576066D1 (de) * | 1984-05-03 | 1990-03-29 | Glaxo Group Ltd | Isochinolinderivate. |
-
1985
- 1985-05-29 GB GB858513460A patent/GB8513460D0/en active Pending
-
1986
- 1986-05-27 DK DK246986A patent/DK246986A/da not_active Application Discontinuation
- 1986-05-28 KR KR1019860004188A patent/KR860009015A/ko not_active Application Discontinuation
- 1986-05-28 DE DE19863617938 patent/DE3617938A1/de not_active Withdrawn
- 1986-05-28 IT IT48070/86A patent/IT1191931B/it active
- 1986-05-28 BE BE0/216713A patent/BE904835A/fr not_active IP Right Cessation
- 1986-05-28 NO NO862120A patent/NO862120L/no unknown
- 1986-05-28 ES ES555407A patent/ES8800942A1/es not_active Expired
- 1986-05-28 NZ NZ216338A patent/NZ216338A/xx unknown
- 1986-05-28 GB GB8612950A patent/GB2175587B/en not_active Expired
- 1986-05-28 SE SE8602434A patent/SE8602434L/xx unknown
- 1986-05-28 CH CH2151/86A patent/CH668596A5/de not_active IP Right Cessation
- 1986-05-29 NL NL8601381A patent/NL8601381A/nl not_active Application Discontinuation
- 1986-05-29 JP JP61122395A patent/JPS6212778A/ja active Pending
- 1986-05-29 FI FI862277A patent/FI862277A/fi not_active Application Discontinuation
- 1986-05-29 ZA ZA864015A patent/ZA864015B/xx unknown
- 1986-05-29 FR FR868607726A patent/FR2584072B1/fr not_active Expired - Fee Related
- 1986-05-29 PH PH33829A patent/PH24002A/en unknown
-
1987
- 1987-08-31 ES ES557703A patent/ES8801212A1/es not_active Expired
- 1987-12-02 PH PH36162A patent/PH24375A/en unknown
-
1988
- 1988-05-28 CH CH2310/88A patent/CH671959A5/de not_active IP Right Cessation
- 1988-09-28 US US07/250,216 patent/US4900737A/en not_active Expired - Fee Related
-
1989
- 1989-12-05 SE SE8904107A patent/SE464523B/sv not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| AU591905B2 (en) | 1989-12-21 |
| ES8800942A1 (es) | 1987-12-01 |
| GB8612950D0 (en) | 1986-07-02 |
| PH24375A (en) | 1990-06-13 |
| AU5807386A (en) | 1986-12-04 |
| ZA864015B (en) | 1988-01-27 |
| CH668596A5 (de) | 1989-01-13 |
| GB2175587B (en) | 1989-10-11 |
| SE8602434D0 (sv) | 1986-05-28 |
| GB8513460D0 (en) | 1985-07-03 |
| KR860009015A (ko) | 1986-12-19 |
| ES557703A0 (es) | 1988-01-01 |
| JPS6212778A (ja) | 1987-01-21 |
| SE464523B (sv) | 1991-05-06 |
| NL8601381A (nl) | 1986-12-16 |
| FI862277A (fi) | 1986-11-30 |
| CH671959A5 (fr) | 1989-10-13 |
| BE904835A (fr) | 1986-11-28 |
| US4900737A (en) | 1990-02-13 |
| GB2175587A (en) | 1986-12-03 |
| FR2584072A1 (fr) | 1987-01-02 |
| FR2584072B1 (fr) | 1991-04-19 |
| DK246986D0 (da) | 1986-05-27 |
| FI862277A0 (fi) | 1986-05-29 |
| DK246986A (da) | 1986-11-30 |
| DE3617938A1 (de) | 1986-12-04 |
| SE8602434L (sv) | 1986-11-30 |
| SE8904107D0 (sv) | 1989-12-05 |
| ES8801212A1 (es) | 1988-01-01 |
| IT1191931B (it) | 1988-03-31 |
| ES555407A0 (es) | 1987-12-01 |
| PH24002A (en) | 1990-02-09 |
| NZ216338A (en) | 1989-03-29 |
| IT8648070A0 (it) | 1986-05-28 |
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