FI59096C - Foerfarande foer framstaellning av nya vinkaminderivat anvaendbara saosom psykostimulanter - Google Patents
Foerfarande foer framstaellning av nya vinkaminderivat anvaendbara saosom psykostimulanter Download PDFInfo
- Publication number
- FI59096C FI59096C FI3552/74A FI355274A FI59096C FI 59096 C FI59096 C FI 59096C FI 3552/74 A FI3552/74 A FI 3552/74A FI 355274 A FI355274 A FI 355274A FI 59096 C FI59096 C FI 59096C
- Authority
- FI
- Finland
- Prior art keywords
- mixture
- formula
- compounds
- vincamine
- ethyl
- Prior art date
Links
- 239000000203 mixture Substances 0.000 claims description 55
- 150000001875 compounds Chemical class 0.000 claims description 53
- 229960002726 vincamine Drugs 0.000 claims description 45
- RXPRRQLKFXBCSJ-GIVPXCGWSA-N vincamine Chemical class C1=CC=C2C(CCN3CCC4)=C5[C@@H]3[C@]4(CC)C[C@](O)(C(=O)OC)N5C2=C1 RXPRRQLKFXBCSJ-GIVPXCGWSA-N 0.000 claims description 27
- 239000002253 acid Substances 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 13
- RXPRRQLKFXBCSJ-UHFFFAOYSA-N dl-Vincamin Natural products C1=CC=C2C(CCN3CCC4)=C5C3C4(CC)CC(O)(C(=O)OC)N5C2=C1 RXPRRQLKFXBCSJ-UHFFFAOYSA-N 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 9
- 230000008569 process Effects 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- 239000007795 chemical reaction product Substances 0.000 claims description 4
- 229910000039 hydrogen halide Inorganic materials 0.000 claims description 4
- 239000012433 hydrogen halide Substances 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 239000003368 psychostimulant agent Substances 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims 1
- 239000000460 chlorine Substances 0.000 claims 1
- 235000019256 formaldehyde Nutrition 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 116
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 72
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- 238000003756 stirring Methods 0.000 description 27
- 229950006936 apovincamine Drugs 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 19
- 229910001868 water Inorganic materials 0.000 description 19
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 18
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 15
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 15
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 15
- 150000004702 methyl esters Chemical class 0.000 description 15
- 239000012071 phase Substances 0.000 description 15
- -1 hydrogen halides Chemical class 0.000 description 14
- 239000002904 solvent Substances 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 239000008346 aqueous phase Substances 0.000 description 11
- 229910052938 sodium sulfate Inorganic materials 0.000 description 10
- 235000011152 sodium sulphate Nutrition 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000007858 starting material Substances 0.000 description 9
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 229910021529 ammonia Inorganic materials 0.000 description 8
- 229950002641 brovincamine Drugs 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 7
- WYIJGAVIVKPUGJ-GIVPXCGWSA-N brovincamine Chemical compound BrC1=CC=C2C(CCN3CCC4)=C5[C@@H]3[C@]4(CC)C[C@](O)(C(=O)OC)N5C2=C1 WYIJGAVIVKPUGJ-GIVPXCGWSA-N 0.000 description 7
- 239000012299 nitrogen atmosphere Substances 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 230000007958 sleep Effects 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 238000002425 crystallisation Methods 0.000 description 6
- 230000008025 crystallization Effects 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 239000006260 foam Substances 0.000 description 6
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 6
- 230000007935 neutral effect Effects 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 238000001228 spectrum Methods 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 239000001569 carbon dioxide Substances 0.000 description 4
- 229910002092 carbon dioxide Inorganic materials 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
- 230000000803 paradoxical effect Effects 0.000 description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 239000002002 slurry Substances 0.000 description 4
- 229910001488 sodium perchlorate Inorganic materials 0.000 description 4
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 150000007975 iminium salts Chemical class 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 210000003625 skull Anatomy 0.000 description 3
- 230000037322 slow-wave sleep Effects 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- JTEJPPKMYBDEMY-UHFFFAOYSA-N 5-methoxytryptamine Chemical compound COC1=CC=C2NC=C(CCN)C2=C1 JTEJPPKMYBDEMY-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 2
- 150000008046 alkali metal hydrides Chemical class 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000002566 electrocorticography Methods 0.000 description 2
- 150000002084 enol ethers Chemical class 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-M fumarate(1-) Chemical compound OC(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-M 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- BTTXESIFAHCXMK-UHFFFAOYSA-N methyl 2-methoxyprop-2-enoate Chemical class COC(=C)C(=O)OC BTTXESIFAHCXMK-UHFFFAOYSA-N 0.000 description 2
- NDYFKPMCFKLPLR-QFIPXVFZSA-N methyl 3-[(3S)-3-ethyl-1-[2-(5-fluoro-1H-indol-3-yl)ethyl]-2-oxopiperidin-3-yl]-2-methoxyprop-2-enoate Chemical compound COC(C(=C[C@]1(C(N(CCC1)CCC1=CNC2=CC=C(C=C12)F)=O)CC)OC)=O NDYFKPMCFKLPLR-QFIPXVFZSA-N 0.000 description 2
- 150000002902 organometallic compounds Chemical class 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 229920000137 polyphosphoric acid Polymers 0.000 description 2
- 235000011056 potassium acetate Nutrition 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- FCGGDEKTUUSBPS-UHFFFAOYSA-M quinolizin-5-ium;perchlorate Chemical compound [O-]Cl(=O)(=O)=O.C1=CC=CC2=CC=CC=[N+]21 FCGGDEKTUUSBPS-UHFFFAOYSA-M 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000008454 sleep-wake cycle Effects 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- BAZAXWOYCMUHIX-UHFFFAOYSA-M sodium perchlorate Chemical compound [Na+].[O-]Cl(=O)(=O)=O BAZAXWOYCMUHIX-UHFFFAOYSA-M 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- MFWFPCPYBKTJDV-JOCHJYFZSA-N (3s)-3-(diethoxymethyl)-3-ethyl-1-[2-(5-fluoro-1h-indol-3-yl)ethyl]piperidin-2-one Chemical compound O=C1[C@@](C(OCC)OCC)(CC)CCCN1CCC1=CNC2=CC=C(F)C=C12 MFWFPCPYBKTJDV-JOCHJYFZSA-N 0.000 description 1
- NVRQFIVFOGYXSC-SFHVURJKSA-N (3s)-3-ethyl-1-[2-(5-fluoro-1h-indol-3-yl)ethyl]-2-oxopiperidine-3-carbaldehyde Chemical compound O=C1[C@](CC)(C=O)CCCN1CCC1=CNC2=CC=C(F)C=C12 NVRQFIVFOGYXSC-SFHVURJKSA-N 0.000 description 1
- DPPZSVRYURJTEW-IBGZPJMESA-N (3s)-3-ethyl-1-[2-(5-methoxy-1h-indol-3-yl)ethyl]-2-oxopiperidine-3-carbaldehyde Chemical compound O=C1[C@](CC)(C=O)CCCN1CCC1=CNC2=CC=C(OC)C=C12 DPPZSVRYURJTEW-IBGZPJMESA-N 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N 1,1-Diethoxyethane Chemical compound CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- VUQMOERHEHTWPE-UHFFFAOYSA-N 1-ethylpiperidin-2-one Chemical compound CCN1CCCCC1=O VUQMOERHEHTWPE-UHFFFAOYSA-N 0.000 description 1
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- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- YIYOVHGQZRQSJT-QFIPXVFZSA-N CC[C@]1(CCCN(C1=O)CCC2=CNC3=C2C=C(C=C3)OC)CC(=C)OC Chemical compound CC[C@]1(CCCN(C1=O)CCC2=CNC3=C2C=C(C=C3)OC)CC(=C)OC YIYOVHGQZRQSJT-QFIPXVFZSA-N 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010021033 Hypomenorrhoea Diseases 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
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
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- WKACQPMBGWZDMR-UHFFFAOYSA-N Vincamin Natural products CC=C1/CN2CCC34CC2C1C(=C3Nc5ccccc45)C=O WKACQPMBGWZDMR-UHFFFAOYSA-N 0.000 description 1
- NGVAIFJVJJFCIM-KUHBDSFDSA-N Vinervidin Natural products CC=C1CN[C@H]2C[C@@H]1[C@@H](C=O)[C@@H]3Nc4ccccc4[C@@H]23 NGVAIFJVJJFCIM-KUHBDSFDSA-N 0.000 description 1
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- RCTYPNKXASFOBE-UHFFFAOYSA-M chloromercury Chemical compound [Hg]Cl RCTYPNKXASFOBE-UHFFFAOYSA-M 0.000 description 1
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- 229940032296 ferric chloride Drugs 0.000 description 1
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- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
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- 238000005984 hydrogenation reaction Methods 0.000 description 1
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- 206010022437 insomnia Diseases 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- NQXWGWZJXJUMQB-UHFFFAOYSA-K iron trichloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].Cl[Fe+]Cl NQXWGWZJXJUMQB-UHFFFAOYSA-K 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- KYMUNKMWGDJFHK-UHFFFAOYSA-N methyl 2-(dimethoxyphosphorylmethoxy)acetate Chemical compound COC(=O)COCP(=O)(OC)OC KYMUNKMWGDJFHK-UHFFFAOYSA-N 0.000 description 1
- XAENXMWMSHMHHJ-QHCPKHFHSA-N methyl 3-[(3s)-3-ethyl-1-[2-(5-methoxy-1h-indol-3-yl)ethyl]-2-oxopiperidin-3-yl]-2-methoxyprop-2-enoate Chemical compound O=C1[C@](CC)(C=C(OC)C(=O)OC)CCCN1CCC1=CNC2=CC=C(OC)C=C12 XAENXMWMSHMHHJ-QHCPKHFHSA-N 0.000 description 1
- VITRIUYHBVKBDH-UHFFFAOYSA-N methyl dimethoxyphosphorylformate Chemical compound COC(=O)P(=O)(OC)OC VITRIUYHBVKBDH-UHFFFAOYSA-N 0.000 description 1
- 210000003205 muscle Anatomy 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
- 210000004237 neck muscle Anatomy 0.000 description 1
- 229940105631 nembutal Drugs 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000005936 piperidyl group Chemical class 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000036385 rapid eye movement (rem) sleep Effects 0.000 description 1
- 239000011833 salt mixture Substances 0.000 description 1
- 230000004620 sleep latency Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000010189 synthetic method 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
- APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical class C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 230000002618 waking effect Effects 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 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
- C07D471/12—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 three hetero rings
- C07D471/14—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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
- C07D209/16—Tryptamines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D461/00—Heterocyclic compounds containing indolo [3,2,1-d,e] pyrido [3,2,1,j] [1,5]-naphthyridine ring systems, e.g. vincamine
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- General Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Psychiatry (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hospice & Palliative Care (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1768973 | 1973-12-18 | ||
| CH1768973A CH588488A5 (en) | 1973-12-18 | 1973-12-18 | Vincamine derivs for treating behaviour disorders - by ring closure of indoloquinolizine deriv |
| CH162174 | 1974-02-06 | ||
| CH162174A CH596207A5 (en) | 1974-02-06 | 1974-02-06 | Vincamine derivs for treating behaviour disorders |
| CH176574 | 1974-02-08 | ||
| CH176574A CH593283A5 (en) | 1974-02-08 | 1974-02-08 | Vincamine derivs for treating behaviour disorders - by ring closure of indoloquinolizine deriv |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI355274A7 FI355274A7 (is") | 1975-06-19 |
| FI59096B FI59096B (fi) | 1981-02-27 |
| FI59096C true FI59096C (fi) | 1981-06-10 |
Family
ID=27173122
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI3552/74A FI59096C (fi) | 1973-12-18 | 1974-12-10 | Foerfarande foer framstaellning av nya vinkaminderivat anvaendbara saosom psykostimulanter |
Country Status (16)
| Country | Link |
|---|---|
| JP (1) | JPS5817474B2 (is") |
| CA (1) | CA1051899A (is") |
| DD (1) | DD116043A5 (is") |
| DE (1) | DE2458164A1 (is") |
| DK (1) | DK139358B (is") |
| ES (3) | ES432952A1 (is") |
| FI (1) | FI59096C (is") |
| FR (1) | FR2254342B1 (is") |
| GB (1) | GB1492579A (is") |
| HK (1) | HK53980A (is") |
| IE (1) | IE40791B1 (is") |
| MY (1) | MY8100186A (is") |
| NL (1) | NL7416237A (is") |
| NO (1) | NO744456L (is") |
| PH (1) | PH12927A (is") |
| SE (1) | SE422798B (is") |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2396759A1 (fr) * | 1977-07-06 | 1979-02-02 | Omnium Chimique Sa | Nouveaux composes heterocycliques, derives de la vincamine, leur preparation et leur application comme medicaments, notamment dans le domaine des insuffisances cardio-circulatoires, cerebro-vasculaires ou respiratoires |
| HU177498B (en) * | 1977-07-27 | 1981-10-28 | Richter Gedeon Vegyeszet | Process for preparing new vincinic acid and apovincinic acid esters |
| FR2423493A1 (fr) * | 1977-10-19 | 1979-11-16 | Omnium Chimique Sa | Nouveaux composes heterocycliques derives de l'apo-vincamine, leur preparation et leur application comme medicaments, notamment dans le domaine des insuffisances cardio-circulatoires, cerebro-vasculaires et respiratoires |
| FR2407931A1 (fr) * | 1977-11-02 | 1979-06-01 | Synthelabo | Derives de l'eburnamenine et leur application en therapeutique |
| JPS5493000A (en) * | 1977-12-28 | 1979-07-23 | Sandoz Ag | Improvement of organic compound |
| DE2800063A1 (de) * | 1978-01-02 | 1979-07-12 | Sandoz Ag | 10-bromvincamin, seine herstellung und verwendung |
| US4315011A (en) * | 1978-07-12 | 1982-02-09 | Richter Gedeon Vegyeszeti Gyar Rt. | 1-Alkyl-9-bromohexahydroindolo quinolizium salts and use thereof to increase blood flow |
| FR2445328A1 (fr) * | 1978-07-12 | 1980-07-25 | Richter Gedeon Vegyeszet | Derives du 14-oxo-e-homo-eburnane, leur procede de preparation et leur utilisation comme medicament |
| US4285949A (en) * | 1978-12-11 | 1981-08-25 | Omnichem Societe Anonyme | Vincamine derivatives, their preparation and therapeutical use |
| HU177732B (en) * | 1978-12-15 | 1981-12-28 | Richter Gedeon Vegyeszet | Process for producing 10-bromo-vincamine and acid additional salts thereof,and 10-bromo-14-epivincamine |
| HU180928B (en) * | 1979-08-06 | 1983-05-30 | Richter Gedeon Vegyeszet | Process for preparing new brominated 15-hydroxy-e-homo-eburane derivatives |
| HU180929B (en) * | 1979-08-13 | 1983-05-30 | Richter Gedeon Vegyeszet | Process for producing new bromo-vincamone derivatives |
| HU185305B (en) * | 1981-08-23 | 1985-01-28 | Richter Gedeon Vegyeszet | Process for preparing vincine and apovincine |
| HU183326B (en) * | 1981-02-11 | 1984-04-28 | Richter Gedeon Vegyeszet | Process for preparing new apovincaminol-3',4',5'-trimethoxy-benzoates substituted in the a ring and acid addition salts thereof |
| ES8604952A1 (es) * | 1985-11-05 | 1986-03-16 | Covex Sa | Procedimiento para la preparacion de los compuestos 10-11 bromo-14,15-dihidro-14 b-hidroxi-(3x,16x)-eburnamenina-14- carboxilato de metilo |
| US4883876A (en) * | 1987-09-07 | 1989-11-28 | Taisho Pharmaceutical Co., Ltd. | Acylated vincaminic acid derivatives |
-
1974
- 1974-12-09 DK DK639774AA patent/DK139358B/da not_active IP Right Cessation
- 1974-12-09 DE DE19742458164 patent/DE2458164A1/de active Granted
- 1974-12-09 SE SE7415416A patent/SE422798B/xx not_active IP Right Cessation
- 1974-12-10 NO NO744456A patent/NO744456L/no unknown
- 1974-12-10 FI FI3552/74A patent/FI59096C/fi active
- 1974-12-13 NL NL7416237A patent/NL7416237A/xx not_active Application Discontinuation
- 1974-12-16 IE IE2591/74A patent/IE40791B1/xx unknown
- 1974-12-16 GB GB54159/74A patent/GB1492579A/en not_active Expired
- 1974-12-16 PH PH16634A patent/PH12927A/en unknown
- 1974-12-16 ES ES432952A patent/ES432952A1/es not_active Expired
- 1974-12-17 CA CA216,230A patent/CA1051899A/en not_active Expired
- 1974-12-17 JP JP49144170A patent/JPS5817474B2/ja not_active Expired
- 1974-12-17 DD DD183107A patent/DD116043A5/xx unknown
- 1974-12-18 FR FR7441717A patent/FR2254342B1/fr not_active Expired
-
1976
- 1976-08-16 ES ES450741A patent/ES450741A1/es not_active Expired
- 1976-08-16 ES ES450740A patent/ES450740A1/es not_active Expired
-
1980
- 1980-09-25 HK HK539/80A patent/HK53980A/xx unknown
-
1981
- 1981-12-30 MY MY186/81A patent/MY8100186A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CA1051899A (en) | 1979-04-03 |
| DK139358C (is") | 1979-07-09 |
| IE40791L (en) | 1975-06-18 |
| DK639774A (is") | 1975-08-25 |
| SE422798B (sv) | 1982-03-29 |
| HK53980A (en) | 1980-10-03 |
| ES450740A1 (es) | 1977-12-16 |
| SE7415416L (is") | 1975-06-19 |
| MY8100186A (en) | 1981-12-31 |
| FR2254342A1 (is") | 1975-07-11 |
| JPS5817474B2 (ja) | 1983-04-07 |
| DE2458164C2 (is") | 1991-04-18 |
| DD116043A5 (is") | 1975-11-05 |
| AU7648374A (en) | 1976-06-17 |
| FI355274A7 (is") | 1975-06-19 |
| NO744456L (is") | 1975-07-14 |
| NL7416237A (nl) | 1975-06-20 |
| GB1492579A (en) | 1977-11-23 |
| FI59096B (fi) | 1981-02-27 |
| PH12927A (en) | 1979-10-10 |
| FR2254342B1 (is") | 1978-07-21 |
| JPS50105700A (is") | 1975-08-20 |
| ES450741A1 (es) | 1978-03-16 |
| DE2458164A1 (de) | 1975-06-26 |
| ES432952A1 (es) | 1977-02-16 |
| IE40791B1 (en) | 1979-08-15 |
| DK139358B (da) | 1979-02-05 |
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