SE454777B - 5-substituerade 3-aminoalkyl-1h-indoler, forfarande for framstellning av dessa och en farmaceutisk komposition for behandling av migren - Google Patents

5-substituerade 3-aminoalkyl-1h-indoler, forfarande for framstellning av dessa och en farmaceutisk komposition for behandling av migren

Info

Publication number: SE454777B
Authority: SE; Sweden
Prior art keywords: group; compound; formula; hydrogen atom; methyl
Prior art date: 1980-08-12

Application number

SE8104783A

Other languages

English (en)

Swedish (sv)

Other versions

SE8104783L (sv

Inventor

I H Coates

K Mills

C F Webb

M D Dowle

D E Bays

Original Assignee

Glaxo Group Ltd

Priority date (The priority date 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 date listed.)

1980-08-12

Filing date

1981-08-11

Publication date

1988-05-30

1981-08-11 Application filed by Glaxo Group Ltd filed Critical Glaxo Group Ltd

1982-02-13 Publication of SE8104783L publication Critical patent/SE8104783L/xx

1988-05-30 Publication of SE454777B publication Critical patent/SE454777B/sv

Links

238000000034 method Methods 0.000 title claims description 29
238000002360 preparation method Methods 0.000 title claims description 11
239000008194 pharmaceutical composition Substances 0.000 title claims description 3
150000002475 indoles Chemical class 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims description 203
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 50
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 49
-1 ethyl [3- (2-aminoethyl) -1H-indol-5-yl] Chemical group 0.000 claims description 47
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 38
239000003054 catalyst Substances 0.000 claims description 37
150000003839 salts Chemical class 0.000 claims description 36
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 32
238000006243 chemical reaction Methods 0.000 claims description 30
229910052739 hydrogen Inorganic materials 0.000 claims description 30
239000001257 hydrogen Substances 0.000 claims description 26
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 24
125000000217 alkyl group Chemical group 0.000 claims description 18
125000004432 carbon atom Chemical group C* 0.000 claims description 17
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
239000002253 acid Substances 0.000 claims description 15
239000012453 solvate Substances 0.000 claims description 14
239000002904 solvent Substances 0.000 claims description 14
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 12
230000008569 process Effects 0.000 claims description 12
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 11
125000005843 halogen group Chemical group 0.000 claims description 11
150000002431 hydrogen Chemical class 0.000 claims description 10
125000006239 protecting group Chemical group 0.000 claims description 10
150000001412 amines Chemical class 0.000 claims description 9
229910052799 carbon Inorganic materials 0.000 claims description 9
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 8
239000003638 chemical reducing agent Substances 0.000 claims description 8
230000009467 reduction Effects 0.000 claims description 8
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 8
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 6
229910021653 sulphate ion Inorganic materials 0.000 claims description 6
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 claims description 6
208000019695 Migraine disease Diseases 0.000 claims description 5
239000003153 chemical reaction reagent Substances 0.000 claims description 5
150000002576 ketones Chemical class 0.000 claims description 5
239000003960 organic solvent Substances 0.000 claims description 5
125000001424 substituent group Chemical group 0.000 claims description 5
229910052783 alkali metal Inorganic materials 0.000 claims description 4
239000003795 chemical substances by application Substances 0.000 claims description 4
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 4
206010027599 migraine Diseases 0.000 claims description 4
238000010992 reflux Methods 0.000 claims description 4
238000007363 ring formation reaction Methods 0.000 claims description 4
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 3
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 3
238000005804 alkylation reaction Methods 0.000 claims description 3
125000002947 alkylene group Chemical group 0.000 claims description 3
239000007822 coupling agent Substances 0.000 claims description 3
235000019253 formic acid Nutrition 0.000 claims description 3
238000010438 heat treatment Methods 0.000 claims description 3
239000000546 pharmaceutical excipient Substances 0.000 claims description 3
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 2
125000004423 acyloxy group Chemical group 0.000 claims description 2
150000001340 alkali metals Chemical class 0.000 claims description 2
230000029936 alkylation Effects 0.000 claims description 2
239000012431 aqueous reaction media Substances 0.000 claims description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 claims description 2
229910052740 iodine Inorganic materials 0.000 claims description 2
ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 claims description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 5
125000003545 alkoxy group Chemical group 0.000 claims 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 5
238000006722 reduction reaction Methods 0.000 claims 3
125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims 2
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 2
239000003377 acid catalyst Substances 0.000 claims 1
125000003342 alkenyl group Chemical group 0.000 claims 1
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims 1
125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
239000000969 carrier Substances 0.000 claims 1
238000010531 catalytic reduction reaction Methods 0.000 claims 1
229910052500 inorganic mineral Inorganic materials 0.000 claims 1
239000011707 mineral Substances 0.000 claims 1
229910052702 rhenium Inorganic materials 0.000 claims 1
229910052707 ruthenium Inorganic materials 0.000 claims 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 163
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 144
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 103
239000000243 solution Substances 0.000 description 99
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 95
DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Natural products CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 89
239000007787 solid Substances 0.000 description 71
239000000203 mixture Substances 0.000 description 66
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
229940109239 creatinine Drugs 0.000 description 45
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 37
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
238000002844 melting Methods 0.000 description 30
230000008018 melting Effects 0.000 description 30
239000003921 oil Substances 0.000 description 29
235000019198 oils Nutrition 0.000 description 29
125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 27
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 25
238000004458 analytical method Methods 0.000 description 25
239000000725 suspension Substances 0.000 description 24
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 20
239000004480 active ingredient Substances 0.000 description 19
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical group CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 18
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
239000000706 filtrate Substances 0.000 description 18
WEVYAHXRMPXWCK-UHFFFAOYSA-N methyl cyanide Natural products CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 17
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
239000000284 extract Substances 0.000 description 15
VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
239000000047 product Substances 0.000 description 13
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
229910052938 sodium sulfate Inorganic materials 0.000 description 12
235000011152 sodium sulphate Nutrition 0.000 description 12
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 11
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 11
239000007864 aqueous solution Substances 0.000 description 11
238000001816 cooling Methods 0.000 description 11
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 10
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 10
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 10
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
238000004440 column chromatography Methods 0.000 description 9
239000011541 reaction mixture Substances 0.000 description 9
229910000029 sodium carbonate Inorganic materials 0.000 description 9
VBGAHRCLHMYZFJ-UHFFFAOYSA-N 2-(5-amino-1h-indol-3-yl)acetonitrile Chemical compound NC1=CC=C2NC=C(CC#N)C2=C1 VBGAHRCLHMYZFJ-UHFFFAOYSA-N 0.000 description 8
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 8
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
239000012267 brine Substances 0.000 description 8
238000000354 decomposition reaction Methods 0.000 description 8
IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 8
239000003480 eluent Substances 0.000 description 8
239000000543 intermediate Substances 0.000 description 8
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
239000012299 nitrogen atmosphere Substances 0.000 description 8
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
229960000583 acetic acid Drugs 0.000 description 6
150000001299 aldehydes Chemical class 0.000 description 6
229910021529 ammonia Inorganic materials 0.000 description 6
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 6
230000015572 biosynthetic process Effects 0.000 description 6
239000006071 cream Substances 0.000 description 6
VCSZKSHWUBFOOE-UHFFFAOYSA-N dioxidanium;sulfate Chemical compound O.O.OS(O)(=O)=O VCSZKSHWUBFOOE-UHFFFAOYSA-N 0.000 description 6
238000001914 filtration Methods 0.000 description 6
239000012280 lithium aluminium hydride Substances 0.000 description 6
229910052943 magnesium sulfate Inorganic materials 0.000 description 6
235000019341 magnesium sulphate Nutrition 0.000 description 6
239000000377 silicon dioxide Substances 0.000 description 6
MEVXSUZBFYZPHZ-UHFFFAOYSA-N 2-amino-3-methyl-4h-imidazol-5-one;sulfuric acid Chemical compound OS(O)(=O)=O.CN1CC(=O)N=C1N MEVXSUZBFYZPHZ-UHFFFAOYSA-N 0.000 description 5
241000400611 Eucalyptus deanei Species 0.000 description 5
150000001408 amides Chemical class 0.000 description 5
239000004202 carbamide Substances 0.000 description 5
239000007858 starting material Substances 0.000 description 5
101100298295 Drosophila melanogaster flfl gene Proteins 0.000 description 4
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
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 4
LGDSHSYDSCRFAB-UHFFFAOYSA-N Methyl isothiocyanate Chemical compound CN=C=S LGDSHSYDSCRFAB-UHFFFAOYSA-N 0.000 description 4
239000007868 Raney catalyst Substances 0.000 description 4
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
229910000564 Raney nickel Inorganic materials 0.000 description 4
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
229920002472 Starch Polymers 0.000 description 4
150000008064 anhydrides Chemical class 0.000 description 4
239000002585 base Substances 0.000 description 4
238000007796 conventional method Methods 0.000 description 4
230000000694 effects Effects 0.000 description 4
150000004677 hydrates Chemical class 0.000 description 4
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
229910000041 hydrogen chloride Inorganic materials 0.000 description 4
238000005984 hydrogenation reaction Methods 0.000 description 4
239000008101 lactose Substances 0.000 description 4
239000010410 layer Substances 0.000 description 4
235000019359 magnesium stearate Nutrition 0.000 description 4
TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical compound COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
239000012429 reaction media Substances 0.000 description 4
239000001632 sodium acetate Substances 0.000 description 4
235000017281 sodium acetate Nutrition 0.000 description 4
239000011780 sodium chloride Substances 0.000 description 4
239000008107 starch Substances 0.000 description 4
235000019698 starch Nutrition 0.000 description 4
KPJZHOPZRAFDTN-ZRGWGRIASA-N (6aR,9R)-N-[(2S)-1-hydroxybutan-2-yl]-4,7-dimethyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-9-carboxamide Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@H](CO)CC)C2)=C3C2=CN(C)C3=C1 KPJZHOPZRAFDTN-ZRGWGRIASA-N 0.000 description 3
DBLQFXNZAWIKCH-UHFFFAOYSA-N 2-[5-(methylamino)-1h-indol-3-yl]acetonitrile Chemical compound CNC1=CC=C2NC=C(CC#N)C2=C1 DBLQFXNZAWIKCH-UHFFFAOYSA-N 0.000 description 3
241000282472 Canis lupus familiaris Species 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
150000001350 alkyl halides Chemical class 0.000 description 3
239000002775 capsule Substances 0.000 description 3
239000003610 charcoal Substances 0.000 description 3
239000000460 chlorine Substances 0.000 description 3
239000012043 crude product Substances 0.000 description 3
239000013078 crystal Substances 0.000 description 3
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
239000006260 foam Substances 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
239000012948 isocyanate Substances 0.000 description 3
150000002513 isocyanates Chemical class 0.000 description 3
150000002540 isothiocyanates Chemical class 0.000 description 3
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 3
229960001186 methysergide Drugs 0.000 description 3
150000002825 nitriles Chemical class 0.000 description 3
229910003445 palladium oxide Inorganic materials 0.000 description 3
JQPTYAILLJKUCY-UHFFFAOYSA-N palladium(ii) oxide Chemical compound [O-2].[Pd+2] JQPTYAILLJKUCY-UHFFFAOYSA-N 0.000 description 3
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 3
239000000843 powder Substances 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
238000007790 scraping Methods 0.000 description 3
239000000829 suppository Substances 0.000 description 3
238000004809 thin layer chromatography Methods 0.000 description 3
WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
NRKYWOKHZRQRJR-UHFFFAOYSA-N 2,2,2-trifluoroacetamide Chemical compound NC(=O)C(F)(F)F NRKYWOKHZRQRJR-UHFFFAOYSA-N 0.000 description 2
FZEUWJICQPZSKM-UHFFFAOYSA-N 2-[5-(aminomethyl)-1h-indol-3-yl]-n-benzyl-n-methylethanamine Chemical compound C=1NC2=CC=C(CN)C=C2C=1CCN(C)CC1=CC=CC=C1 FZEUWJICQPZSKM-UHFFFAOYSA-N 0.000 description 2
LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
PUPOHAOGJQTRCJ-UHFFFAOYSA-N 3-(cyanomethyl)-5-(dimethylsulfamoylamino)-1h-indole Chemical compound CN(C)S(=O)(=O)NC1=CC=C2NC=C(CC#N)C2=C1 PUPOHAOGJQTRCJ-UHFFFAOYSA-N 0.000 description 2
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239000001923 methylcellulose Substances 0.000 description 1
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
XGEGHDBEHXKFPX-NJFSPNSNSA-N methylurea Chemical compound [14CH3]NC(N)=O XGEGHDBEHXKFPX-NJFSPNSNSA-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
238000003801 milling Methods 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
SQNVFBHILRFQJY-UHFFFAOYSA-N n-(methylsulfamoyl)methanamine Chemical compound CNS(=O)(=O)NC SQNVFBHILRFQJY-UHFFFAOYSA-N 0.000 description 1
HXEVGLDMPHPLKX-UHFFFAOYSA-N n-[3-(2-aminoethyl)-1h-indol-5-yl]-n-methylformamide Chemical compound O=CN(C)C1=CC=C2NC=C(CCN)C2=C1 HXEVGLDMPHPLKX-UHFFFAOYSA-N 0.000 description 1
ITHBNVLQFOSPKC-UHFFFAOYSA-N n-[3-(2-aminoethyl)-1h-indol-5-yl]acetamide Chemical compound CC(=O)NC1=CC=C2NC=C(CCN)C2=C1 ITHBNVLQFOSPKC-UHFFFAOYSA-N 0.000 description 1
YLRPTTKDZJKCJZ-UHFFFAOYSA-N n-[3-(cyanomethyl)-1h-indol-5-yl]-n-methylformamide Chemical compound O=CN(C)C1=CC=C2NC=C(CC#N)C2=C1 YLRPTTKDZJKCJZ-UHFFFAOYSA-N 0.000 description 1
IIKYMHZOTYMFFU-UHFFFAOYSA-N n-[[3-(2-aminoethyl)-1h-indol-5-yl]methyl]formamide Chemical compound C1=C(CNC=O)C=C2C(CCN)=CNC2=C1 IIKYMHZOTYMFFU-UHFFFAOYSA-N 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
238000010647 peptide synthesis reaction Methods 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
230000001376 precipitating effect Effects 0.000 description 1
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
239000008213 purified water Substances 0.000 description 1
230000007017 scission Effects 0.000 description 1
238000007086 side reaction Methods 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
QAHVHSLSRLSVGS-UHFFFAOYSA-N sulfamoyl chloride Chemical class NS(Cl)(=O)=O QAHVHSLSRLSVGS-UHFFFAOYSA-N 0.000 description 1
125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 1
230000006103 sulfonylation Effects 0.000 description 1
238000005694 sulfonylation reaction Methods 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
150000003609 titanium compounds Chemical class 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
125000005490 tosylate group Chemical group 0.000 description 1
230000009466 transformation Effects 0.000 description 1
238000000844 transformation Methods 0.000 description 1
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
210000003462 vein Anatomy 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- 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
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
- 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
- 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
- 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
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Indole Compounds (AREA)

SE8104783A 1980-08-12 1981-08-11 5-substituerade 3-aminoalkyl-1h-indoler, forfarande for framstellning av dessa och en farmaceutisk komposition for behandling av migren SE454777B (sv)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB8026288		1980-08-12
GB8026287		1980-08-12

Publications (2)

Publication Number	Publication Date
SE8104783L SE8104783L (sv)	1982-02-13
SE454777B true SE454777B (sv)	1988-05-30

Family

ID=26276534

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SE8104783A SE454777B (sv)	1980-08-12	1981-08-11	5-substituerade 3-aminoalkyl-1h-indoler, forfarande for framstellning av dessa och en farmaceutisk komposition for behandling av migren

Country Status (12)

Country	Link
AU (1)	AU550010B2 (da)
CH (1)	CH652394A5 (da)
DE (1)	DE3131752A1 (da)
DK (1)	DK157995C (da)
ES (2)	ES504694A0 (da)
FR (1)	FR2488606A1 (da)
GB (1)	GB2083463B (da)
IE (1)	IE51493B1 (da)
IT (1)	IT1171450B (da)
NL (1)	NL8103764A (da)
NZ (1)	NZ197998A (da)
SE (1)	SE454777B (da)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IT1170387B (it) *	1982-06-07	1987-06-03	Glaxo Group Ltd	Composti eterociclici, procedimento per prepararli e composizioni farmaceutiche che li contengono
PT78358B (en) *	1983-04-07	1986-05-30	Smith Kline French Lab	Chemical process
GB8332437D0 (en) *	1983-12-06	1984-01-11	Glaxo Group Ltd	Chemical compounds
HU196752B (en) *	1983-12-06	1989-01-30	Glaxo Group Ltd	Process for production of medical compositions containing indole-derivatives and these compounds
GB8419575D0 (en) *	1984-08-01	1984-09-05	Glaxo Group Ltd	Chemical compounds
GB8600397D0 (en) *	1986-01-08	1986-02-12	Glaxo Group Ltd	Chemical compounds
GB8600398D0 (en) *	1986-01-08	1986-02-12	Glaxo Group Ltd	Chemical compounds
GB8607824D0 (en) *	1986-03-27	1986-04-30	Glaxo Group Ltd	Chemical compounds
US5225431A (en) *	1987-10-23	1993-07-06	Burroughs Wellcome Co.	Therapeutic substituted indole compounds and compositions thereof
SK278998B6 (sk) *	1991-02-01	1998-05-06	Merck Sharp & Dohme Limited	Deriváty imidazolu, triazolu a tetrazolu, spôsob i
GB9104136D0 (en) *	1991-02-27	1991-04-17	Merck Sharp & Dohme	Therapeutic agents
GB9207930D0 (en) *	1992-04-10	1992-05-27	Pfizer Ltd	Indoles
DK0635015T3 (da) *	1992-04-10	1997-03-17	Pfizer	Acylaminoindolderivater som 5-Htl agonister
GB9209882D0 (en) *	1992-05-07	1992-06-24	Glaxo Lab Sa	Compositions
GB9211277D0 (en)	1992-05-28	1992-07-15	Glaxo Group Inc	Pharmaceutical compositions
IL106445A (en) *	1992-07-30	1998-01-04	Merck Sharp & Dohme	History of 1,2,4-Trans-Triazole 4-Transform, Preparation and Pharmaceutical Preparations Containing Them
ES2070772B1 (es) *	1993-08-09	1996-02-16	Pfizer	Derivados de acilaminoindol
US6025374A (en) *	1994-12-06	2000-02-15	Merck Sharp & Dohme, Ltd.	Azetidine, pyrrolidine and piperidine derivatives as 5HT1 receptor agonists
FR2731224B1 (fr) *	1995-03-02	1997-05-30	Pf Medicament	Nouveaux derives bi-tryptaminiques sulfonamides, leur procede de preparation et leur utilisation a titre de medicaments
US7189753B1 (en)	1997-11-06	2007-03-13	Cady Roger K	Preemptive prophylaxis of migraine

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US2870162A (en) *	1954-04-28	1959-01-20	Upjohn Co	Production of certain tryptamines and compounds produced in the process
FR1203195A (fr) *	1958-07-25	1960-01-15	Chimiotherapie Lab Franc	Procédé de préparation d'un nouveau dérivé de la tryptamine
NL7316677A (da) *	1972-12-21	1974-06-25
ZA795239B (en) *	1978-10-12	1980-11-26	Glaxo Group Ltd	Heterocyclic compounds

1981
- 1981-08-11 SE SE8104783A patent/SE454777B/sv not_active IP Right Cessation
- 1981-08-11 IE IE1832/81A patent/IE51493B1/en unknown
- 1981-08-11 NZ NZ197998A patent/NZ197998A/en unknown
- 1981-08-11 GB GB8124478A patent/GB2083463B/en not_active Expired
- 1981-08-11 FR FR8115515A patent/FR2488606A1/fr active Granted
- 1981-08-11 DK DK357281A patent/DK157995C/da not_active IP Right Cessation
- 1981-08-11 ES ES504694A patent/ES504694A0/es active Granted
- 1981-08-11 AU AU73995/81A patent/AU550010B2/en not_active Ceased
- 1981-08-11 CH CH5161/81A patent/CH652394A5/fr not_active IP Right Cessation
- 1981-08-11 IT IT49085/81A patent/IT1171450B/it active
- 1981-08-11 DE DE19813131752 patent/DE3131752A1/de active Granted
- 1981-08-11 NL NL8103764A patent/NL8103764A/nl not_active Application Discontinuation
1982
- 1982-07-13 ES ES513934A patent/ES8405371A1/es not_active Expired

Also Published As

Publication number	Publication date
SE8104783L (sv)	1982-02-13
GB2083463A (en)	1982-03-24
ES513934A0 (es)	1984-06-01
AU550010B2 (en)	1986-02-27
AU7399581A (en)	1982-02-18
IT8149085A0 (it)	1981-08-11
IE51493B1 (en)	1987-01-07
FR2488606B1 (da)	1984-10-26
CH652394A5 (fr)	1985-11-15
DE3131752A1 (de)	1982-06-16
ES8405371A1 (es)	1984-06-01
NZ197998A (en)	1985-08-16
IT1171450B (it)	1987-06-10
DK157995B (da)	1990-03-12
DE3131752C2 (da)	1992-04-23
NL8103764A (nl)	1982-03-01
DK357281A (da)	1982-02-13
DK157995C (da)	1990-08-06
IE811832L (en)	1982-02-12
ES8300699A1 (es)	1982-11-01
FR2488606A1 (fr)	1982-02-19
ES504694A0 (es)	1982-11-01
GB2083463B (en)	1984-05-10

Publication	Publication Date	Title
SE454777B (sv)	1988-05-30	5-substituerade 3-aminoalkyl-1h-indoler, forfarande for framstellning av dessa och en farmaceutisk komposition for behandling av migren
SE454881B (sv)	1988-06-06	N-(3-(aminoalkyl)-1h-indol-5-yl-metyl) sulfonamider, forfarande for framstellning av dessa och en farmaceutisk komposition for behandling av migren
US5571833A (en)	1996-11-05	Tryptamine analogues, their synthesis and their use as 5-HT1 -like or 5-HT2 receptor agonists
US6093735A (en)	2000-07-25	Selective β-3 adrenergic agonists
SE454880B (sv)	1988-06-06	3-aminoalkyl-1h-indol-5-acetamider, forfarande for framstellning av dessa och en farmaceutisk komposition for behandling av migren
US6075040A (en)	2000-06-13	Selective β3 adrenergic agonists
HU196752B (en)	1989-01-30	Process for production of medical compositions containing indole-derivatives and these compounds
US4839377A (en)	1989-06-13	5-substituted 3-aminoalkyl indoles
US5726177A (en)	1998-03-10	Indole-derived arylpiperazines as ligands for 5HT1 -like, 5HT1B and 5HT1D receptors
CZ280529B6 (cs)	1996-02-14	Indolové deriváty, způsob výroby a farmaceutické prostředky s jejich obsahem
SE452460B (sv)	1987-11-30	3-/2-(dimetylamino)etyl/-n-metyl-1h-indol-5-metansulfonamid, en farmaceutisk komposition innehallande denna och ett forfarande for framstellning av foreningen
SE448628B (sv)	1987-03-09	5-indolamider, farmaceutisk komposition innehallande dessa och forfarande for framstellning av foreningarna
JP2001106685A (ja)	2001-04-17	ゴナドトロピン放出ホルモン拮抗剤
US6046227A (en)	2000-04-04	Selective β3 adrenergic agonists
HU199791B (en)	1990-03-28	Process for producing carboxamides comprising indolyl and indazolyl group
NL8700027A (nl)	1987-08-03	Chemische verbindingen.
US4898863A (en)	1990-02-06	Heterocyclic carboxamides
MX2010010446A (es)	2010-11-05	Derivados de (hetero)arilo ciclohexano.
WO1999010344A1 (fr)	1999-03-04	Derives d'indole comme agonistes de 5-ht1b et 5-ht1d
NL8701372A (nl)	1988-01-04	Indoolderivaten, werkwijze ter bereiding daarvan alsmede farmaceutische preparaten die deze derivaten als actieve component bevatten.
JP2001525398A (ja)	2001-12-11	選択的β３アドレナリン作動性アゴニスト
EP0782568A1 (fr)	1997-07-09	Ethers aromatiques derives d'indoles comme "5ht1-like" ligands
US5770611A (en)	1998-06-23	Indole derivatives as 5HT1 -like agonists
DK165976B (da)	1993-02-22	5-aminosulfonyl-methyl-indolderivater og farmaceutiske praeparater med indhold deraf
AU5599799A (en)	1999-12-23	Aromatic ethers derived from indols such as 5HT1-like ligands

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