DE2351184A1 - Isochinolinderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneipraeparate - Google Patents
Isochinolinderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneipraeparateInfo
- Publication number
- DE2351184A1 DE2351184A1 DE19732351184 DE2351184A DE2351184A1 DE 2351184 A1 DE2351184 A1 DE 2351184A1 DE 19732351184 DE19732351184 DE 19732351184 DE 2351184 A DE2351184 A DE 2351184A DE 2351184 A1 DE2351184 A1 DE 2351184A1
- Authority
- DE
- Germany
- Prior art keywords
- bromide
- formula
- radical
- monohydrate
- compound
- 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.)
- Pending
Links
- 150000001875 compounds Chemical class 0.000 title claims description 25
- 238000000034 method Methods 0.000 title claims description 14
- 238000002360 preparation method Methods 0.000 title claims description 13
- 150000002537 isoquinolines Chemical class 0.000 title claims description 11
- 230000008569 process Effects 0.000 title claims description 9
- 238000004519 manufacturing process Methods 0.000 title description 4
- -1 alkynyl radical Chemical class 0.000 claims description 74
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical group [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- 239000004480 active ingredient Substances 0.000 claims description 10
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 10
- 150000003254 radicals Chemical class 0.000 claims description 9
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 6
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical group [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 239000000969 carrier Substances 0.000 claims description 5
- 150000004682 monohydrates Chemical class 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 4
- PUCMKBHSNNRNGN-UHFFFAOYSA-M 2-(2-methylisoquinolin-2-ium-6-yl)oxyethanamine;bromide Chemical compound [Br-].C1=C(OCCN)C=CC2=C[N+](C)=CC=C21 PUCMKBHSNNRNGN-UHFFFAOYSA-M 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 150000005840 aryl radicals Chemical group 0.000 claims description 3
- GVLGAFRNYJVHBC-UHFFFAOYSA-N hydrate;hydrobromide Chemical compound O.Br GVLGAFRNYJVHBC-UHFFFAOYSA-N 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 239000002798 polar solvent Substances 0.000 claims description 3
- 238000010992 reflux Methods 0.000 claims description 3
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical group CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 claims description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 2
- YVRAKDOVJVZEHY-UHFFFAOYSA-M 6-methoxy-2-methylisoquinolin-2-ium;iodide Chemical compound [I-].C1=[N+](C)C=CC2=CC(OC)=CC=C21 YVRAKDOVJVZEHY-UHFFFAOYSA-M 0.000 claims description 2
- XAKBSHICSHRJCL-UHFFFAOYSA-N [CH2]C(=O)C1=CC=CC=C1 Chemical group [CH2]C(=O)C1=CC=CC=C1 XAKBSHICSHRJCL-UHFFFAOYSA-N 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 150000001450 anions Chemical class 0.000 claims description 2
- 125000003435 aroyl group Chemical group 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
- 235000019253 formic acid Nutrition 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical group OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 claims description 2
- 150000007529 inorganic bases Chemical class 0.000 claims description 2
- 150000004694 iodide salts Chemical group 0.000 claims description 2
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims description 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims 2
- 125000004103 aminoalkyl group Chemical group 0.000 claims 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims 2
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims 2
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 claims 2
- YURYZEMMQVIXGO-UHFFFAOYSA-M 1-benzyl-6-methoxy-2-methylisoquinolin-2-ium;iodide;hydrate Chemical compound O.[I-].C[N+]=1C=CC2=CC(OC)=CC=C2C=1CC1=CC=CC=C1 YURYZEMMQVIXGO-UHFFFAOYSA-M 0.000 claims 1
- ALDQTEXDCPDZFI-UHFFFAOYSA-M 2-methyl-6-pentoxyisoquinolin-2-ium;bromide;hydrate Chemical compound O.[Br-].C1=[N+](C)C=CC2=CC(OCCCCC)=CC=C21 ALDQTEXDCPDZFI-UHFFFAOYSA-M 0.000 claims 1
- OWNUNPXDHIYINW-UHFFFAOYSA-M 6-ethoxy-2,3-dimethylisoquinolin-2-ium;bromide;hydrate Chemical compound O.[Br-].C1=[N+](C)C(C)=CC2=CC(OCC)=CC=C21 OWNUNPXDHIYINW-UHFFFAOYSA-M 0.000 claims 1
- SHYRLQNNWCHCKK-UHFFFAOYSA-M 6-methoxy-1-(4-methoxyphenyl)-2-methylisoquinolin-2-ium;chloride Chemical compound [Cl-].C1=CC(OC)=CC=C1C1=[N+](C)C=CC2=CC(OC)=CC=C12 SHYRLQNNWCHCKK-UHFFFAOYSA-M 0.000 claims 1
- 125000004416 alkarylalkyl group Chemical group 0.000 claims 1
- 125000006196 aroyl alkyl group Chemical group 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- ZYCMDWDFIQDPLP-UHFFFAOYSA-N hbr bromine Chemical compound Br.Br ZYCMDWDFIQDPLP-UHFFFAOYSA-N 0.000 claims 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
- FWFGVMYFCODZRD-UHFFFAOYSA-N oxidanium;hydrogen sulfate Chemical compound O.OS(O)(=O)=O FWFGVMYFCODZRD-UHFFFAOYSA-N 0.000 claims 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 42
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 description 6
- IGGGWGBPSWUADK-UHFFFAOYSA-N 6-ethoxyisoquinoline Chemical compound C1=NC=CC2=CC(OCC)=CC=C21 IGGGWGBPSWUADK-UHFFFAOYSA-N 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- TXJMCXHDSDDIIY-UHFFFAOYSA-N 2-methylisoquinolin-2-ium-6-ol;bromide Chemical compound [Br-].C1=C(O)C=CC2=C[N+](C)=CC=C21 TXJMCXHDSDDIIY-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 229940123208 Biguanide Drugs 0.000 description 3
- 241000282472 Canis lupus familiaris Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000002168 alkylating agent Substances 0.000 description 3
- 229940100198 alkylating agent Drugs 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000000575 pesticide Substances 0.000 description 3
- ICFJFFQQTFMIBG-UHFFFAOYSA-N phenformin Chemical compound NC(=N)NC(=N)NCCC1=CC=CC=C1 ICFJFFQQTFMIBG-UHFFFAOYSA-N 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 235000009518 sodium iodide Nutrition 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 2
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 239000001828 Gelatine Substances 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 150000005485 alkoxyisoquinolines Chemical class 0.000 description 2
- 239000011260 aqueous acid Substances 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- 150000004283 biguanides Chemical class 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- HFPZCAJZSCWRBC-UHFFFAOYSA-N p-cymene Chemical compound CC(C)C1=CC=C(C)C=C1 HFPZCAJZSCWRBC-UHFFFAOYSA-N 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 229960003243 phenformin Drugs 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 150000003459 sulfonic acid esters Chemical class 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- CHZXTOCAICMPQR-UHFFFAOYSA-N 2-(2-bromoethyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCBr)C(=O)C2=C1 CHZXTOCAICMPQR-UHFFFAOYSA-N 0.000 description 1
- GDEOHZKOKRRBDC-UHFFFAOYSA-M 2-(6-ethoxyisoquinolin-2-ium-2-yl)ethanamine;bromide Chemical compound [Br-].C1=[N+](CCN)C=CC2=CC(OCC)=CC=C21 GDEOHZKOKRRBDC-UHFFFAOYSA-M 0.000 description 1
- XMFJBDMRVGNPGN-UHFFFAOYSA-M 2-(6-ethoxyisoquinolin-2-ium-2-yl)ethanol;bromide Chemical compound [Br-].C1=[N+](CCO)C=CC2=CC(OCC)=CC=C21 XMFJBDMRVGNPGN-UHFFFAOYSA-M 0.000 description 1
- XCWPJGKRBLGNEU-UHFFFAOYSA-M 2-[2-(2-methylisoquinolin-2-ium-6-yl)oxyethyl]isoindole-1,3-dione;bromide Chemical compound [Br-].O=C1C2=CC=CC=C2C(=O)N1CCOC1=CC2=CC=[N+](C)C=C2C=C1 XCWPJGKRBLGNEU-UHFFFAOYSA-M 0.000 description 1
- UYRNVPVBHXRFBX-UHFFFAOYSA-M 2-benzyl-6-methoxyisoquinolin-2-ium;bromide Chemical compound [Br-].C1=CC2=CC(OC)=CC=C2C=[N+]1CC1=CC=CC=C1 UYRNVPVBHXRFBX-UHFFFAOYSA-M 0.000 description 1
- JJFOBACUIRKUPN-UHFFFAOYSA-N 2-bromoethoxybenzene Chemical compound BrCCOC1=CC=CC=C1 JJFOBACUIRKUPN-UHFFFAOYSA-N 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- YBGDWMTWERRXPN-UHFFFAOYSA-M 2-methyl-6-phenylmethoxyisoquinolin-2-ium;bromide Chemical compound [Br-].C1=CC2=C[N+](C)=CC=C2C=C1OCC1=CC=CC=C1 YBGDWMTWERRXPN-UHFFFAOYSA-M 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- SLEHYCPTJRGREJ-UHFFFAOYSA-N 4-methylbenzenesulfonic acid;oxolan-3-ol Chemical compound OC1CCOC1.CC1=CC=C(S(O)(=O)=O)C=C1 SLEHYCPTJRGREJ-UHFFFAOYSA-N 0.000 description 1
- OWKFCXAKXQPMOO-UHFFFAOYSA-M 6-ethoxy-2-methylisoquinolin-2-ium;bromide;hydrate Chemical compound O.[Br-].C1=[N+](C)C=CC2=CC(OCC)=CC=C21 OWKFCXAKXQPMOO-UHFFFAOYSA-M 0.000 description 1
- XZNUJESLPUNSNO-UHFFFAOYSA-N 6-methoxyisoquinoline Chemical compound C1=NC=CC2=CC(OC)=CC=C21 XZNUJESLPUNSNO-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 description 1
- 238000006407 Bischler-Napieralski reaction Methods 0.000 description 1
- 244000278792 Calathea allouia Species 0.000 description 1
- 235000007487 Calathea allouia Nutrition 0.000 description 1
- KIWBPDUYBMNFTB-UHFFFAOYSA-N Ethyl hydrogen sulfate Chemical compound CCOS(O)(=O)=O KIWBPDUYBMNFTB-UHFFFAOYSA-N 0.000 description 1
- 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 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
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 238000006929 Pictet-Spengler synthesis reaction Methods 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- KMGBZBJJOKUPIA-UHFFFAOYSA-N butyl iodide Chemical compound CCCCI KMGBZBJJOKUPIA-UHFFFAOYSA-N 0.000 description 1
- XAAHAAMILDNBPS-UHFFFAOYSA-L calcium hydrogenphosphate dihydrate Chemical compound O.O.[Ca+2].OP([O-])([O-])=O XAAHAAMILDNBPS-UHFFFAOYSA-L 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
- QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical group C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 description 1
- BESCFIAGVMCBAI-UHFFFAOYSA-N ethyl n-(2-bromoethyl)carbamate Chemical compound CCOC(=O)NCCBr BESCFIAGVMCBAI-UHFFFAOYSA-N 0.000 description 1
- GIFLBTUMFMWBBB-UHFFFAOYSA-N ethyl n-[2-(6-ethoxyisoquinolin-2-ium-2-yl)ethyl]carbamate;bromide Chemical compound [Br-].C1=C(OCC)C=CC2=C[N+](CCNC(=O)OCC)=CC=C21 GIFLBTUMFMWBBB-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003337 fertilizer Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- XDYHDLLKHFVVSE-UHFFFAOYSA-N hydrate;dihydrobromide Chemical compound O.Br.Br XDYHDLLKHFVVSE-UHFFFAOYSA-N 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- SHLPPXXKRFINFY-UHFFFAOYSA-N isoquinolin-2-ium;bromide Chemical compound Br.C1=NC=CC2=CC=CC=C21 SHLPPXXKRFINFY-UHFFFAOYSA-N 0.000 description 1
- GPVPDRHTRGTSIH-UHFFFAOYSA-N isoquinolin-6-ol Chemical compound C1=NC=CC2=CC(O)=CC=C21 GPVPDRHTRGTSIH-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 229940117803 phenethylamine Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 150000003839 salts Chemical group 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
Classifications
-
- 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
- C07D217/10—Quaternary compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/14—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals
- C07D217/16—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals substituted by oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB4821172A GB1407685A (en) | 1972-10-19 | 1972-10-19 | Isoquinolinium compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2351184A1 true DE2351184A1 (de) | 1974-05-02 |
Family
ID=10447780
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19732351184 Pending DE2351184A1 (de) | 1972-10-19 | 1973-10-11 | Isochinolinderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneipraeparate |
Country Status (15)
| Country | Link |
|---|---|
| JP (1) | JPS49132081A (enExample) |
| AT (1) | AT333283B (enExample) |
| BE (1) | BE806131A (enExample) |
| CA (1) | CA1019743A (enExample) |
| CH (1) | CH598224A5 (enExample) |
| DE (1) | DE2351184A1 (enExample) |
| DK (1) | DK134013B (enExample) |
| ES (1) | ES419660A1 (enExample) |
| FR (1) | FR2203629B1 (enExample) |
| GB (1) | GB1407685A (enExample) |
| IE (1) | IE38339B1 (enExample) |
| LU (1) | LU68628A1 (enExample) |
| NL (1) | NL7314378A (enExample) |
| SE (1) | SE402286B (enExample) |
| ZA (1) | ZA737712B (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9322828D0 (en) * | 1993-11-05 | 1993-12-22 | Sandoz Ltd | Organic compounds |
| US7067529B2 (en) * | 2003-05-19 | 2006-06-27 | Hoffmann-La Roche Inc. | Glutamine fructose-y-phosphate amidotransferase (GFAT) inhibitors |
| JP2007508338A (ja) * | 2003-10-16 | 2007-04-05 | エフ．ホフマン−ラ ロシュ アーゲー | グルタミンフルクトース−６−リン酸アミドトランスフェラーゼ（ｇｆａｔ）インヒビター |
| FR3135816A1 (fr) | 2022-05-20 | 2023-11-24 | Elno | Connecteur électrique militarisé destiné à être connecté à un équipement audio, câble de connexion et système audio associés |
-
1972
- 1972-10-19 GB GB4821172A patent/GB1407685A/en not_active Expired
-
1973
- 1973-10-01 IE IE1747/73A patent/IE38339B1/xx unknown
- 1973-10-02 ZA ZA737712A patent/ZA737712B/xx unknown
- 1973-10-11 DE DE19732351184 patent/DE2351184A1/de active Pending
- 1973-10-15 ES ES419660A patent/ES419660A1/es not_active Expired
- 1973-10-16 AT AT878373A patent/AT333283B/de not_active IP Right Cessation
- 1973-10-16 BE BE136736A patent/BE806131A/xx unknown
- 1973-10-16 CA CA183,479A patent/CA1019743A/en not_active Expired
- 1973-10-16 LU LU68628A patent/LU68628A1/xx unknown
- 1973-10-18 DK DK564673AA patent/DK134013B/da unknown
- 1973-10-18 NL NL7314378A patent/NL7314378A/xx not_active Application Discontinuation
- 1973-10-18 SE SE7314205A patent/SE402286B/xx unknown
- 1973-10-18 JP JP48117362A patent/JPS49132081A/ja active Pending
- 1973-10-18 CH CH1472273A patent/CH598224A5/xx not_active IP Right Cessation
- 1973-10-18 FR FR7337198A patent/FR2203629B1/fr not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| AT333283B (de) | 1976-11-10 |
| CA1019743A (en) | 1977-10-25 |
| NL7314378A (enExample) | 1974-04-23 |
| FR2203629A1 (enExample) | 1974-05-17 |
| IE38339B1 (en) | 1978-02-15 |
| SE402286B (sv) | 1978-06-26 |
| IE38339L (en) | 1974-04-19 |
| ZA737712B (en) | 1974-08-28 |
| CH598224A5 (enExample) | 1978-04-28 |
| DK134013B (da) | 1976-08-30 |
| GB1407685A (en) | 1975-09-24 |
| DK134013C (enExample) | 1977-01-31 |
| AU6123573A (en) | 1975-04-10 |
| JPS49132081A (enExample) | 1974-12-18 |
| BE806131A (fr) | 1974-04-16 |
| FR2203629B1 (enExample) | 1976-07-02 |
| ATA878373A (de) | 1976-03-15 |
| LU68628A1 (enExample) | 1973-12-27 |
| ES419660A1 (es) | 1976-07-01 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| OHA | Expiration of time for request for examination |