CH671017A5 - - Google Patents

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Publication number: CH671017A5
Authority: CH; Switzerland
Prior art keywords: group; indole; ethyl; compound; compounds
Prior art date: 1986-01-08

Application number

CH46/87A

Other languages

English (en)

French (fr)

Inventor

Keith Mills

Ian Harold Coates

David Edmund Bays

Colin Frederick Webb

Michael Dennis Dowle

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.)

1986-01-08

Filing date

1987-01-08

Publication date

1989-07-31

1987-01-08 Application filed by Glaxo Group Ltd filed Critical Glaxo Group Ltd

1989-07-31 Publication of CH671017A5 publication Critical patent/CH671017A5/fr

Links

150000001875 compounds Chemical class 0.000 description 124
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 104
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 96
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 72
239000000203 mixture Substances 0.000 description 48
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
239000000243 solution Substances 0.000 description 45
DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 41
235000019441 ethanol Nutrition 0.000 description 41
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
239000000543 intermediate Substances 0.000 description 39
150000003839 salts Chemical class 0.000 description 39
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 38
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 37
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 34
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 32
238000000034 method Methods 0.000 description 28
239000003921 oil Substances 0.000 description 28
235000019198 oils Nutrition 0.000 description 28
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
239000007787 solid Substances 0.000 description 27
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 25
238000006243 chemical reaction Methods 0.000 description 25
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
-1 carboxylic acid chlorides Chemical class 0.000 description 23
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 22
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
229940109239 creatinine Drugs 0.000 description 22
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
125000004435 hydrogen atom Chemical group [H]* 0.000 description 20
230000009467 reduction Effects 0.000 description 20
238000006722 reduction reaction Methods 0.000 description 20
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 20
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 19
230000008569 process Effects 0.000 description 18
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
239000001257 hydrogen Substances 0.000 description 16
229910052739 hydrogen Inorganic materials 0.000 description 16
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
239000006260 foam Substances 0.000 description 15
239000002253 acid Substances 0.000 description 14
238000003756 stirring Methods 0.000 description 14
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 13
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
239000003054 catalyst Substances 0.000 description 13
239000000725 suspension Substances 0.000 description 13
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 12
238000005481 NMR spectroscopy Methods 0.000 description 12
150000002148 esters Chemical class 0.000 description 12
239000000284 extract Substances 0.000 description 12
238000002360 preparation method Methods 0.000 description 12
229910000029 sodium carbonate Inorganic materials 0.000 description 12
235000017550 sodium carbonate Nutrition 0.000 description 12
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 11
239000004480 active ingredient Substances 0.000 description 11
229910021529 ammonia Inorganic materials 0.000 description 11
229910052757 nitrogen Inorganic materials 0.000 description 11
239000012453 solvate Substances 0.000 description 11
239000002904 solvent Substances 0.000 description 11
239000003826 tablet Substances 0.000 description 11
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
238000001816 cooling Methods 0.000 description 10
239000000047 product Substances 0.000 description 10
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
125000000217 alkyl group Chemical group 0.000 description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
238000004809 thin layer chromatography Methods 0.000 description 9
238000011282 treatment Methods 0.000 description 9
239000007832 Na2SO4 Substances 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
150000001408 amides Chemical class 0.000 description 8
239000003638 chemical reducing agent Substances 0.000 description 8
238000004587 chromatography analysis Methods 0.000 description 8
230000008570 general process Effects 0.000 description 8
229910052943 magnesium sulfate Inorganic materials 0.000 description 8
235000019341 magnesium sulphate Nutrition 0.000 description 8
239000012044 organic layer Substances 0.000 description 8
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 8
229910052938 sodium sulfate Inorganic materials 0.000 description 8
235000011152 sodium sulphate Nutrition 0.000 description 8
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 7
208000019695 Migraine disease Diseases 0.000 description 7
150000001299 aldehydes Chemical class 0.000 description 7
239000010410 layer Substances 0.000 description 7
206010027599 migraine Diseases 0.000 description 7
150000002825 nitriles Chemical class 0.000 description 7
238000010992 reflux Methods 0.000 description 7
238000007363 ring formation reaction Methods 0.000 description 7
125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 6
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
150000001412 amines Chemical class 0.000 description 6
239000002585 base Substances 0.000 description 6
238000001914 filtration Methods 0.000 description 6
125000005843 halogen group Chemical group 0.000 description 6
229910052740 iodine Inorganic materials 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 6
235000006408 oxalic acid Nutrition 0.000 description 6
239000002244 precipitate Substances 0.000 description 6
239000012429 reaction media Substances 0.000 description 6
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 5
239000003377 acid catalyst Substances 0.000 description 5
239000007864 aqueous solution Substances 0.000 description 5
125000004429 atom Chemical group 0.000 description 5
239000003153 chemical reaction reagent Substances 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 5
239000003814 drug Substances 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
238000003818 flash chromatography Methods 0.000 description 5
239000012458 free base Substances 0.000 description 5
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 5
150000002475 indoles Chemical class 0.000 description 5
229910052751 metal Inorganic materials 0.000 description 5
239000002184 metal Substances 0.000 description 5
239000003960 organic solvent Substances 0.000 description 5
125000003884 phenylalkyl group Chemical group 0.000 description 5
239000000377 silicon dioxide Substances 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 4
IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 4
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
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 4
239000012359 Methanesulfonyl chloride Substances 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
239000000443 aerosol Substances 0.000 description 4
229910052783 alkali metal Inorganic materials 0.000 description 4
150000001350 alkyl halides Chemical class 0.000 description 4
239000002168 alkylating agent Substances 0.000 description 4
229940100198 alkylating agent Drugs 0.000 description 4
150000008064 anhydrides Chemical class 0.000 description 4
125000003710 aryl alkyl group Chemical group 0.000 description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
239000000460 chlorine Substances 0.000 description 4
230000000694 effects Effects 0.000 description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
229910052500 inorganic mineral Inorganic materials 0.000 description 4
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
235000010755 mineral Nutrition 0.000 description 4
239000011707 mineral Substances 0.000 description 4
238000005192 partition Methods 0.000 description 4
239000008194 pharmaceutical composition Substances 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
239000000843 powder Substances 0.000 description 4
125000006239 protecting group Chemical group 0.000 description 4
238000000746 purification Methods 0.000 description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
239000011734 sodium Substances 0.000 description 4
239000011780 sodium chloride Substances 0.000 description 4
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
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 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
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 3
229920000388 Polyphosphate Polymers 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 3
125000004423 acyloxy group Chemical group 0.000 description 3
150000001340 alkali metals Chemical class 0.000 description 3
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
229940054051 antipsychotic indole derivative Drugs 0.000 description 3
239000012431 aqueous reaction media Substances 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
239000012267 brine Substances 0.000 description 3
239000002775 capsule Substances 0.000 description 3
229910052801 chlorine Inorganic materials 0.000 description 3
238000007906 compression Methods 0.000 description 3
230000006835 compression Effects 0.000 description 3
125000000753 cycloalkyl group Chemical group 0.000 description 3
239000012634 fragment Substances 0.000 description 3
238000007429 general method Methods 0.000 description 3
150000004677 hydrates Chemical class 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
150000002576 ketones Chemical class 0.000 description 3
239000008101 lactose Substances 0.000 description 3
239000012280 lithium aluminium hydride Substances 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
239000001205 polyphosphate Substances 0.000 description 3
235000011176 polyphosphates Nutrition 0.000 description 3
229910052703 rhodium Inorganic materials 0.000 description 3
239000010948 rhodium Substances 0.000 description 3
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
238000010561 standard procedure Methods 0.000 description 3
125000001424 substituent group Chemical group 0.000 description 3
239000005526 vasoconstrictor agent Substances 0.000 description 3
ADZUEEUKBYCSEY-UHFFFAOYSA-N 1h-indole-5-carbaldehyde Chemical compound O=CC1=CC=C2NC=CC2=C1 ADZUEEUKBYCSEY-UHFFFAOYSA-N 0.000 description 2
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
229920002785 Croscarmellose sodium Polymers 0.000 description 2
239000004338 Dichlorodifluoromethane Substances 0.000 description 2
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
CKXBFQJLDAMMGM-UHFFFAOYSA-N N-[2-[3-[2-(methylamino)ethyl]-1H-indol-5-yl]ethyl]methanesulfonamide Chemical compound CNCCC1=CNC2=CC=C(CCNS(C)(=O)=O)C=C12 CKXBFQJLDAMMGM-UHFFFAOYSA-N 0.000 description 2
208000002193 Pain Diseases 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
150000001241 acetals Chemical class 0.000 description 2
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 2
125000002252 acyl group Chemical group 0.000 description 2
230000010933 acylation Effects 0.000 description 2
238000005917 acylation reaction Methods 0.000 description 2
125000003342 alkenyl group Chemical group 0.000 description 2
125000005907 alkyl ester group Chemical group 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
238000010533 azeotropic distillation Methods 0.000 description 2
CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
229910052796 boron Inorganic materials 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 2
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 2
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
150000001735 carboxylic acids Chemical class 0.000 description 2
238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
VZDYWEUILIUIDF-UHFFFAOYSA-J cerium(4+);disulfate Chemical compound [Ce+4].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O VZDYWEUILIUIDF-UHFFFAOYSA-J 0.000 description 2
229910000355 cerium(IV) sulfate Inorganic materials 0.000 description 2
239000003610 charcoal Substances 0.000 description 2
239000003245 coal Substances 0.000 description 2
239000007822 coupling agent Substances 0.000 description 2
229960001681 croscarmellose sodium Drugs 0.000 description 2
235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 2
239000013078 crystal Substances 0.000 description 2
235000019700 dicalcium phosphate Nutrition 0.000 description 2
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 2
235000019404 dichlorodifluoromethane Nutrition 0.000 description 2
230000010339 dilation Effects 0.000 description 2
238000007907 direct compression Methods 0.000 description 2
238000006073 displacement reaction Methods 0.000 description 2
229940079593 drug Drugs 0.000 description 2
XCGSFFUVFURLIX-VFGNJEKYSA-N ergotamine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2C(C=3C=CC=C4NC=C(C=34)C2)=C1)C)C1=CC=CC=C1 XCGSFFUVFURLIX-VFGNJEKYSA-N 0.000 description 2
229960004943 ergotamine Drugs 0.000 description 2
XCGSFFUVFURLIX-UHFFFAOYSA-N ergotaminine Natural products C1=C(C=2C=CC=C3NC=C(C=23)C2)C2N(C)CC1C(=O)NC(C(N12)=O)(C)OC1(O)C1CCCN1C(=O)C2CC1=CC=CC=C1 XCGSFFUVFURLIX-UHFFFAOYSA-N 0.000 description 2
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235000010199 sorbic acid Nutrition 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
235000010356 sorbitol Nutrition 0.000 description 1
241000894007 species Species 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
229940032147 starch Drugs 0.000 description 1
150000003890 succinate salts Chemical class 0.000 description 1
229940124530 sulfonamide Drugs 0.000 description 1
150000003871 sulfonates Chemical class 0.000 description 1
229940032330 sulfuric acid Drugs 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 1
FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 1
125000005490 tosylate group Chemical group 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
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
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
229940029284 trichlorofluoromethane Drugs 0.000 description 1
125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 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
229910052721 tungsten Inorganic materials 0.000 description 1
229910052720 vanadium Inorganic materials 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
238000005550 wet granulation Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
239000008096 xylene Substances 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
- 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
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Pain & Pain Management (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Indole Compounds (AREA)

CH46/87A 1986-01-08 1987-01-08 CH671017A5 (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GB868600398A GB8600398D0 (en)	1986-01-08	1986-01-08	Chemical compounds

Publications (1)

Publication Number	Publication Date
CH671017A5 true CH671017A5 (de)	1989-07-31

Family

ID=10591075

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CH46/87A CH671017A5 (de)	1986-01-08	1987-01-08

Country Status (11)

Country	Link
JP (1)	JPS62228057A (de)
AT (1)	AT386197B (de)
AU (1)	AU597324B2 (de)
BE (1)	BE1000072A4 (de)
CH (1)	CH671017A5 (de)
DE (1)	DE3700407A1 (de)
FR (1)	FR2595352B1 (de)
GB (2)	GB8600398D0 (de)
IT (1)	IT1216772B (de)
NL (1)	NL8700027A (de)
ZA (1)	ZA87104B (de)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB8600397D0 (en) *	1986-01-08	1986-02-12	Glaxo Group Ltd	Chemical compounds
US5225431A (en) *	1987-10-23	1993-07-06	Burroughs Wellcome Co.	Therapeutic substituted indole compounds and compositions thereof
GB8819024D0 (en) *	1988-08-10	1988-09-14	Glaxo Group Ltd	Chemical compounds
WO1991018897A1 (en) *	1990-06-07	1991-12-12	The Wellcome Foundation Limited	Therapeutic heterocyclic compounds
GB9012672D0 (en) *	1990-06-07	1990-08-01	Wellcome Found	Therapeutic heterocyclic compounds
TW263508B (de) *	1991-02-12	1995-11-21	Pfizer
US5206377A (en) *	1991-12-05	1993-04-27	Whitby Research, Inc.	Compounds useful as antiproliferative agents
GB9201038D0 (en) *	1992-01-16	1992-03-11	Glaxo Group Ltd	Chemical compounds
US5409941A (en) *	1992-02-03	1995-04-25	Pfizer Inc.	5-heteroyl indole derivatives
GB9211277D0 (en)	1992-05-28	1992-07-15	Glaxo Group Inc	Pharmaceutical compositions
US5496957A (en) *	1993-09-01	1996-03-05	Virginia Commonwealth University	Tryptamine analogs with 5-HT1D selectivity
CA2147991A1 (en) *	1993-09-01	1995-03-09	Richard A. Glennon	Tryptamine analogs with 5-ht1d selectivity
WO2004056769A2 (en) *	2002-12-20	2004-07-08	Ciba Specialty Chemicals Holding Inc.	Synthesis of amines and intermediates for the synthesis thereof

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB147107A (en) *	1915-04-06	1921-10-07	Zeiss Carl	Improvements in finders for photographic apparatus
GB145459A (en) *	1917-03-24	1921-04-21	Anschuetz & Co Gmbh	Improvements in indicators for the turning of aircraft about a vertical axis
ZA795239B (en) *	1978-10-12	1980-11-26	Glaxo Group Ltd	Heterocyclic compounds
SE454777B (sv) *	1980-08-12	1988-05-30	Glaxo Group Ltd	5-substituerade 3-aminoalkyl-1h-indoler, forfarande for framstellning av dessa och en farmaceutisk komposition for behandling av migren
ZW19381A1 (en) *	1980-08-12	1983-03-09	Glaxo Group Ltd	Heterocyclic compounds
GB8600397D0 (en) *	1986-01-08	1986-02-12	Glaxo Group Ltd	Chemical compounds
FR2903394B1 (fr) *	2006-07-05	2008-09-19	Pierre Marcelli	Devidoir a mandrin expansible pour bobine
CN102317964B (zh) *	2007-04-06	2016-04-06	盖亚软件Ip有限公司	一种内容分发系统和分发内容的方法

1986
- 1986-01-08 GB GB868600398A patent/GB8600398D0/en active Pending
1987
- 1987-01-08 GB GB8700381A patent/GB2186874B/en not_active Expired - Fee Related
- 1987-01-08 ZA ZA87104A patent/ZA87104B/xx unknown
- 1987-01-08 IT IT8747506A patent/IT1216772B/it active
- 1987-01-08 DE DE19873700407 patent/DE3700407A1/de not_active Withdrawn
- 1987-01-08 FR FR878700108A patent/FR2595352B1/fr not_active Expired - Fee Related
- 1987-01-08 AU AU67418/87A patent/AU597324B2/en not_active Ceased
- 1987-01-08 AT AT0002487A patent/AT386197B/de not_active IP Right Cessation
- 1987-01-08 BE BE8700004A patent/BE1000072A4/fr not_active IP Right Cessation
- 1987-01-08 NL NL8700027A patent/NL8700027A/nl not_active Application Discontinuation
- 1987-01-08 CH CH46/87A patent/CH671017A5/fr not_active IP Right Cessation
- 1987-01-08 JP JP62002590A patent/JPS62228057A/ja active Pending

Also Published As

Publication number	Publication date
GB8600398D0 (en)	1986-02-12
FR2595352A1 (fr)	1987-09-11
ZA87104B (en)	1987-12-30
DE3700407A1 (de)	1987-07-09
IT1216772B (it)	1990-03-14
AU6741887A (en)	1987-07-09
ATA2487A (de)	1987-12-15
GB8700381D0 (en)	1987-02-11
GB2186874A (en)	1987-08-26
GB2186874B (en)	1990-02-07
BE1000072A4 (fr)	1988-02-02
NL8700027A (nl)	1987-08-03
AU597324B2 (en)	1990-05-31
IT8747506A0 (it)	1987-01-08
FR2595352B1 (fr)	1990-07-13
AT386197B (de)	1988-07-11
JPS62228057A (ja)	1987-10-06

Publication	Publication Date	Title
BE1000071A4 (fr)	1988-02-02	Derives d'indole, procede pour leur preparation et compositions pharmaceutiques les contenant.
FR2568571A1 (fr)	1986-02-07	Derive d'indole
FR2530625A1 (fr)	1984-01-27	Derives d'indole, procedes pour leur preparation et compositions pharmaceutiques les contenant
CH651551A5 (fr)	1985-09-30	Derives de l'indole, leur preparation et compositions pharmaceutiques les contenant.
CH663411A5 (fr)	1987-12-15	Derives d'indole utiles comme medicaments.
EP0147107B1 (de)	1989-08-02	Indolderivate
FR2488605A1 (fr)	1982-02-19	Derives de l'indole, leur preparation et leurs utilisations therapeutiques
JPH0148896B2 (de)	1989-10-20
LU87414A1 (fr)	1989-07-07	Derives de l'adenosine
CH664152A5 (fr)	1988-02-15	Derives de tetrahydrocarbazolones.
CH652394A5 (fr)	1985-11-15	Derives indoliques, leur preparation et medicaments les renfermant.
CH667647A5 (fr)	1988-10-31	5-alkenesulfonamides indoles.
FR2882054A1 (fr)	2006-08-18	Derives de 1,5-diarylpyrrole, leur preparation et leur application en therapeutique
CH671017A5 (de)	1989-07-31
EP0611766A1 (de)	1994-08-24	Polysubstituierte 2-Amidothiazole-Derivate, Verfahren zu ihrer Herstellung, pharmazeutische Zusammenstellungen die sie enthalten und ihre Anwendung für die Bereitung eines Arzneimittels
CH667454A5 (fr)	1988-10-14	Derives d'indoles.
EP0677042B1 (de)	1998-07-22	Indol-piperazin-derivate als selektive liganden der 5ht1d und 5ht1b receptoren verwendbar als arzneimittel
EP1007524B1 (de)	2003-11-12	Indolderivate als 5-ht1b und 5-ht1d agonisten
CH673841A5 (de)	1990-04-12
EP1242389A2 (de)	2002-09-25	Verzweigte substituierte aminoderivate vom 3-amino-1-phenyl-1h[1,2,4]triazol, verfahren zu deren herstellung und sie enthaltende pharmazeutische zusammensetzungen
LU87129A1 (fr)	1988-09-20	Nouvel acide piperazinecarboxylique,sa preparation et son utilisation comme medicament
US4876267A (en)	1989-10-24	5-Aminosulphoryl substituted indole derivatives
FR2884824A1 (fr)	2006-10-27	Derives de 1h-pyrimido[4,5-b]indole, leur preparation et leur application en therapeutique
LU85915A1 (fr)	1986-01-14	Nouveaux derives d'indole utiles comme medicaments et intermediaires et procedes pour leur preparation

Legal Events

Date	Code	Title	Description
1993-09-30	PL	Patent ceased
2024-10-31	PL	Patent ceased