CZ359292A3 - Anti-migrainous 4-pyrimidinyl- and 4-pyridyl derivatives of indol-2-yl-alkyl piperazines - Google Patents
Anti-migrainous 4-pyrimidinyl- and 4-pyridyl derivatives of indol-2-yl-alkyl piperazines Download PDFInfo
- Publication number
- CZ359292A3 CZ359292A3 CS923592A CS359292A CZ359292A3 CZ 359292 A3 CZ359292 A3 CZ 359292A3 CS 923592 A CS923592 A CS 923592A CS 359292 A CS359292 A CS 359292A CZ 359292 A3 CZ359292 A3 CZ 359292A3
- Authority
- CZ
- Czechia
- Prior art keywords
- solution
- mmol
- propyl
- methoxy
- indolyl
- Prior art date
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- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 title description 2
- 208000001407 Vascular Headaches Diseases 0.000 claims abstract description 10
- -1 alkoxy radicals Chemical class 0.000 claims description 124
- 150000001875 compounds Chemical class 0.000 claims description 103
- 229910052739 hydrogen Inorganic materials 0.000 claims description 76
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 28
- 125000000217 alkyl group Chemical group 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 19
- 239000001257 hydrogen Substances 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 150000002431 hydrogen Chemical group 0.000 claims description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
- IDMFVGRBITWGLW-UHFFFAOYSA-N 5-methoxy-4-piperazin-1-ylpyrimidine Chemical compound COC1=CN=CN=C1N1CCNCC1 IDMFVGRBITWGLW-UHFFFAOYSA-N 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical group 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 239000012453 solvate Substances 0.000 claims description 3
- QLEIDMAURCRVCX-UHFFFAOYSA-N 1-propylpiperazine Chemical compound CCCN1CCNCC1 QLEIDMAURCRVCX-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- RZQIGQUOKAWBDA-UHFFFAOYSA-N 3-[3-[4-(3-methoxypyridin-4-yl)-2-methylpiperazin-1-yl]propyl]-1h-indole Chemical compound COC1=CN=CC=C1N1CC(C)N(CCCC=2C3=CC=CC=C3NC=2)CC1 RZQIGQUOKAWBDA-UHFFFAOYSA-N 0.000 claims 1
- OBGFIOQZOFKHJX-UHFFFAOYSA-N 5-nitro-2-propyl-1h-indole Chemical compound [O-][N+](=O)C1=CC=C2NC(CCC)=CC2=C1 OBGFIOQZOFKHJX-UHFFFAOYSA-N 0.000 claims 1
- 206010007134 Candida infections Diseases 0.000 claims 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims 1
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims 1
- 125000002071 phenylalkoxy group Chemical class 0.000 claims 1
- 238000007910 systemic administration Methods 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 9
- 239000003795 chemical substances by application Substances 0.000 abstract description 5
- 230000003389 potentiating effect Effects 0.000 abstract description 4
- 102100027493 5-hydroxytryptamine receptor 1D Human genes 0.000 abstract 1
- 101710138068 5-hydroxytryptamine receptor 1D Proteins 0.000 abstract 1
- 239000000556 agonist Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 280
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 211
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 208
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 165
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 132
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 126
- 239000011541 reaction mixture Substances 0.000 description 103
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 92
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 86
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 69
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 64
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 64
- 239000000741 silica gel Substances 0.000 description 56
- 229910002027 silica gel Inorganic materials 0.000 description 56
- 238000000034 method Methods 0.000 description 55
- 239000000203 mixture Substances 0.000 description 52
- 235000019441 ethanol Nutrition 0.000 description 47
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 46
- 238000001914 filtration Methods 0.000 description 45
- 239000000706 filtrate Substances 0.000 description 43
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
- 238000004458 analytical method Methods 0.000 description 42
- 229910052799 carbon Inorganic materials 0.000 description 42
- 238000001816 cooling Methods 0.000 description 42
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 39
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 36
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 36
- 239000000047 product Substances 0.000 description 36
- 239000007787 solid Substances 0.000 description 36
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 34
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 34
- 238000010992 reflux Methods 0.000 description 34
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 32
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 31
- 238000004587 chromatography analysis Methods 0.000 description 31
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 29
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 26
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
- 239000000725 suspension Substances 0.000 description 26
- 229910052757 nitrogen Inorganic materials 0.000 description 24
- 208000019695 Migraine disease Diseases 0.000 description 23
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 23
- 229910000027 potassium carbonate Inorganic materials 0.000 description 23
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 21
- 235000011114 ammonium hydroxide Nutrition 0.000 description 21
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 21
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 20
- 239000000284 extract Substances 0.000 description 20
- 206010027599 migraine Diseases 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- 206010019233 Headaches Diseases 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- 239000000126 substance Substances 0.000 description 18
- 231100000869 headache Toxicity 0.000 description 17
- 229920006395 saturated elastomer Polymers 0.000 description 17
- 239000012141 concentrate Substances 0.000 description 16
- 239000000543 intermediate Substances 0.000 description 16
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 15
- 235000017557 sodium bicarbonate Nutrition 0.000 description 15
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- 239000002244 precipitate Substances 0.000 description 14
- 229910052786 argon Inorganic materials 0.000 description 13
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- 230000008569 process Effects 0.000 description 12
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 229910000029 sodium carbonate Inorganic materials 0.000 description 11
- 238000001228 spectrum Methods 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 239000012267 brine Substances 0.000 description 10
- 238000002425 crystallisation Methods 0.000 description 10
- 230000008025 crystallization Effects 0.000 description 10
- 238000001035 drying Methods 0.000 description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
- 239000011780 sodium chloride Substances 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 235000008504 concentrate Nutrition 0.000 description 9
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 8
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical class OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 8
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 8
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- 239000003054 catalyst Substances 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 229940076279 serotonin Drugs 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- IJQIGKLDBGKSNT-UHFFFAOYSA-N 4,6-dichloro-5-methoxypyrimidine Chemical compound COC1=C(Cl)N=CN=C1Cl IJQIGKLDBGKSNT-UHFFFAOYSA-N 0.000 description 5
- GLNLORIMKOOXGK-UHFFFAOYSA-N 5-methoxy-4-(2-methylpiperazin-1-yl)pyrimidine Chemical compound COC1=CN=CN=C1N1C(C)CNCC1 GLNLORIMKOOXGK-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 5
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 5
- 238000005804 alkylation reaction Methods 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 5
- FRYHCSODNHYDPU-UHFFFAOYSA-N ethanesulfonyl chloride Chemical compound CCS(Cl)(=O)=O FRYHCSODNHYDPU-UHFFFAOYSA-N 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 239000006260 foam Substances 0.000 description 5
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
- 229960004592 isopropanol Drugs 0.000 description 5
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 5
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 5
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 238000005694 sulfonylation reaction Methods 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- JOMNTHCQHJPVAZ-UHFFFAOYSA-N 2-methylpiperazine Chemical compound CC1CNCCN1 JOMNTHCQHJPVAZ-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 208000002193 Pain Diseases 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
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- 230000029936 alkylation Effects 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 4
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- AALNXQUZNZCZND-UHFFFAOYSA-N n-(1h-indol-5-yl)ethanesulfonamide Chemical compound CCS(=O)(=O)NC1=CC=C2NC=CC2=C1 AALNXQUZNZCZND-UHFFFAOYSA-N 0.000 description 4
- 230000036407 pain Effects 0.000 description 4
- 235000010288 sodium nitrite Nutrition 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 230000006103 sulfonylation Effects 0.000 description 4
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 4
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 4
- 230000002792 vascular Effects 0.000 description 4
- 239000003039 volatile agent Substances 0.000 description 4
- 239000011592 zinc chloride Substances 0.000 description 4
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- XINMFEAHXJVBRG-UHFFFAOYSA-N 1-[3-(3-hydroxypropyl)-1h-indol-5-yl]-n-methylmethanesulfonamide Chemical compound CNS(=O)(=O)CC1=CC=C2NC=C(CCCO)C2=C1 XINMFEAHXJVBRG-UHFFFAOYSA-N 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- CTMIYYREUVYVEL-UHFFFAOYSA-N 4-chloro-5-methoxypyrimidine Chemical compound COC1=CN=CN=C1Cl CTMIYYREUVYVEL-UHFFFAOYSA-N 0.000 description 3
- OKESCPJZXOUZBO-UHFFFAOYSA-N 5-ethoxypyrimidine Chemical compound CCOC1=CN=CN=C1 OKESCPJZXOUZBO-UHFFFAOYSA-N 0.000 description 3
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- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 3
- 101100153154 Escherichia phage T5 thy gene Proteins 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 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 3
- QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-N 0.000 description 3
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- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
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- 239000004323 potassium nitrate Substances 0.000 description 1
- 235000010333 potassium nitrate Nutrition 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- DKORSYDQYFVQNS-UHFFFAOYSA-N propyl methanesulfonate Chemical compound CCCOS(C)(=O)=O DKORSYDQYFVQNS-UHFFFAOYSA-N 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011946 reduction process Methods 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 1
- 229960003147 reserpine Drugs 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000003762 serotonin receptor affecting agent Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 238000011125 single therapy Methods 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- SXZUSZBEGNFCDZ-UHFFFAOYSA-M sodium;(4-nitrophenyl)methanesulfonate Chemical compound [Na+].[O-][N+](=O)C1=CC=C(CS([O-])(=O)=O)C=C1 SXZUSZBEGNFCDZ-UHFFFAOYSA-M 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000001119 stannous chloride Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- KQKPFRSPSRPDEB-UHFFFAOYSA-N sumatriptan Chemical compound CNS(=O)(=O)CC1=CC=C2NC=C(CCN(C)C)C2=C1 KQKPFRSPSRPDEB-UHFFFAOYSA-N 0.000 description 1
- 229960003708 sumatriptan Drugs 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 description 1
- 229940095064 tartrate Drugs 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
- 238000005496 tempering Methods 0.000 description 1
- IMYAFQPVYRRWAR-UHFFFAOYSA-N tert-butyl 4-(5-methoxypyrimidin-4-yl)-3-methylpiperazine-1-carboxylate Chemical compound COC1=CN=CN=C1N1C(C)CN(C(=O)OC(C)(C)C)CC1 IMYAFQPVYRRWAR-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- XJNDPQUDIJOVGI-UHFFFAOYSA-N tert-butyl-dimethyl-pent-1-ynoxysilane Chemical compound CCCC#CO[Si](C)(C)C(C)(C)C XJNDPQUDIJOVGI-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 101150072314 thyA gene Proteins 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pain & Pain Management (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US81066191A | 1991-12-19 | 1991-12-19 | |
| US95959292A | 1992-10-13 | 1992-10-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CZ359292A3 true CZ359292A3 (en) | 1994-01-19 |
Family
ID=27123378
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS923592A CZ359292A3 (en) | 1991-12-19 | 1992-12-07 | Anti-migrainous 4-pyrimidinyl- and 4-pyridyl derivatives of indol-2-yl-alkyl piperazines |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US5434154A (en:Method) |
| EP (1) | EP0548813A1 (en:Method) |
| JP (1) | JPH05262762A (en:Method) |
| CN (1) | CN1085556A (en:Method) |
| AU (1) | AU661527B2 (en:Method) |
| CA (1) | CA2084531A1 (en:Method) |
| CZ (1) | CZ359292A3 (en:Method) |
| FI (1) | FI925737L (en:Method) |
| IL (1) | IL104024A (en:Method) |
| MX (1) | MX9207114A (en:Method) |
| NO (1) | NO302522B1 (en:Method) |
| NZ (1) | NZ245439A (en:Method) |
| PH (1) | PH30988A (en:Method) |
| RU (1) | RU2114111C1 (en:Method) |
| TW (1) | TW221420B (en:Method) |
Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5521188A (en) * | 1993-09-16 | 1996-05-28 | Bristol-Myers Squibb Company | Antimigraine cyclobutenedione derivatives of indolylalkyl-pyridinyl and pyrimidinylpiperazines |
| CA2130078A1 (en) * | 1993-09-16 | 1995-03-17 | Jonas A. Gylys | Antimigraine cyclobutenedione derivatives of indolylalkyl-pyridinyl and pyrimidinylpiperazines |
| US5468768A (en) * | 1994-01-06 | 1995-11-21 | Bristol-Myers Squibb Company | Antimigraine derivatives of indolylcycloalkanylamines |
| GB9410031D0 (en) * | 1994-05-19 | 1994-07-06 | Merck Sharp & Dohme | Therapeutic agents |
| US5807857A (en) * | 1994-05-19 | 1998-09-15 | Merck Sharp & Dohme Ltd. | Piperazine, piperidine and tetrahydropyridine derivative of indol-3-alkyl as 5-HT1D-α agonists |
| US5552402A (en) * | 1994-05-19 | 1996-09-03 | Merck, Sharp & Dohme Ltd. | Five-membered heteroaromatic compounds as 5-HT receptor agonists |
| US5567824A (en) * | 1994-05-24 | 1996-10-22 | Merck & Co., Inc. | Palladium catalyzed ring closure of triazolyltryptamine |
| ES2079323B1 (es) * | 1994-06-21 | 1996-10-16 | Vita Invest Sa | Derivados de indol utiles para el tratamiento de la migraña, composicion y uso correspondientes. |
| GB9415575D0 (en) * | 1994-08-02 | 1994-09-21 | Merck Sharp & Dohme | Therapeutic agents |
| US5550239A (en) * | 1994-11-08 | 1996-08-27 | Bristol-Myers Squibb Company | Process for large-scale production of indolyl alkyl pyrimidinyl piperazine compounds |
| GB9423682D0 (en) * | 1994-11-23 | 1995-01-11 | Merck Sharp & Dohme | Therapeutic agents |
| GB9501865D0 (en) * | 1995-01-31 | 1995-03-22 | Merck Sharp & Dohme | Therapeutic agents |
| US5618816A (en) * | 1995-03-02 | 1997-04-08 | Bristol-Myers Squibb Company | Antimigraine 1,2,5-thiadiazole derivatives of indolylalkyl-pyridnyl and pyrimidinylpiperazines |
| US5889010A (en) * | 1995-05-18 | 1999-03-30 | Pfizer Inc. | Benzimidazole derivatives having dopaminergic activity |
| JPH11510177A (ja) * | 1995-08-07 | 1999-09-07 | メルク シヤープ エンド ドーム リミテツド | 置換１−インドリルプロピル−４−フェネチルピペラジン誘導体 |
| JPH09124643A (ja) * | 1995-08-14 | 1997-05-13 | Bristol Myers Squibb Co | 抗うつ作用を有する１−アリールアルキル−４−（アルコキシピリジニル）−又は４−（アルコキシピリミジニル）ピペラジン誘導体 |
| GB9519563D0 (en) * | 1995-09-26 | 1995-11-29 | Merck Sharp & Dohme | Therapeutic agents |
| AU711165B2 (en) * | 1995-09-28 | 1999-10-07 | Merck Sharp & Dohme Limited | Substituted indolylpropyl-piperazine derivatives as 5-ht1dalpha agonists |
| WO1997016446A1 (en) * | 1995-11-02 | 1997-05-09 | Merck Sharp & Dohme Limited | Bicyclic heteroaryl-alkylene-(homo)piperazinones and thione analogues thereof, their preparation and their use as selective agonists of 5-ht1-like receptors |
| GB9523250D0 (en) * | 1995-11-14 | 1996-01-17 | Merck Sharp & Dohme | Therapeutic agents |
| GB9609374D0 (en) * | 1996-05-03 | 1996-07-10 | Merck Sharp & Dohme | Therapeutic agents |
| US5808064A (en) * | 1996-08-13 | 1998-09-15 | Merck & Co., Inc. | Palladium catalyzed indolization |
| US5877329A (en) * | 1996-08-13 | 1999-03-02 | Merck & Co., Inc. | Palladium catalyzed indolization |
| US5811551A (en) * | 1996-08-13 | 1998-09-22 | Merck & Co., Inc. | Palladium catalyzed indolization |
| US5891885A (en) * | 1996-10-09 | 1999-04-06 | Algos Pharmaceutical Corporation | Method for treating migraine |
| GB9714383D0 (en) * | 1997-07-08 | 1997-09-10 | Pfizer Ltd | Improved process |
| DE19756036A1 (de) * | 1997-12-17 | 1999-06-24 | Merck Patent Gmbh | Amid- und Harnstoffderivate |
| US6864262B2 (en) * | 2000-11-29 | 2005-03-08 | Eli Lilly And Company | 1-(2-m-methanesulfonamidophenylethyl)-4-(m-trifluoromethylphenyl) piperazine and pharmaceutically acceptable salts and solvents thereof |
| DE10102944A1 (de) * | 2001-01-23 | 2002-07-25 | Merck Patent Gmbh | Verfahren zur Herstellung von (3-Cyan-1H-indol-7-yl)-[4-(4-fluorphenethyl)-piperazin-1-yl]-methanon und dessen Salzen |
| US20030017175A1 (en) * | 2001-07-05 | 2003-01-23 | R.T. Alamo Ventures I, Inc. | Sublingual administration of dihydroergotamine for the treatment of migraine |
| US6685951B2 (en) | 2001-07-05 | 2004-02-03 | R. T. Alamo Ventures I, Inc. | Administration of dihydroergotamine as a sublingual spray or aerosol for the treatment of migraine |
| US20030198669A1 (en) * | 2001-07-05 | 2003-10-23 | R.T. Alamo Ventures I, Llc | Compositions and methods for rapid dissolving formulations of dihydroergotamine and caffeine for the treatment of migraine |
| DE60233076D1 (de) | 2002-02-13 | 2009-09-03 | Meiji Dairies Corp | Indolderivate substituiert mit langkettigen alcoholen und sie enthaltende arzneimittel |
| DE102004047517A1 (de) * | 2004-09-28 | 2006-03-30 | Merck Patent Gmbh | Neuartige Kristallform von (3-Cyan-1H-indol-7-yl)-[4-(4-fluorphenethyl)-piperazin-1-yl]-methanon, Hydrochlorid |
| WO2006129190A1 (en) * | 2005-06-03 | 2006-12-07 | Glenmark Pharmaceuticals Limited | Process for the preparation of almotriptan |
| RU2461556C2 (ru) * | 2006-12-30 | 2012-09-20 | Эбботт Гмбх Унд Ко. Кг | Замещенные производные оксидола и их применение в качестве лигандов рецептора вазопрессина |
| CN101677954A (zh) | 2007-02-11 | 2010-03-24 | Map药物公司 | 治疗性施用dhe用于快速减轻偏头痛而使副作用分布最小化的方法 |
| EP2036888A1 (en) * | 2007-09-17 | 2009-03-18 | Laboratorios del Dr. Esteve S.A. | Naphthyl-substituted sulfonamides |
| WO2013016223A2 (en) | 2011-07-22 | 2013-01-31 | The University Of Chicago | Treatments for migraine and related disorders |
| EP2935280A4 (en) | 2012-12-21 | 2016-05-25 | Map Pharmaceuticals Inc | 8'-HYDROXY-DIHYDROERGOTAMINE COMPOUNDS AND COMPOSITIONS |
| CN104163813B (zh) * | 2013-05-16 | 2017-02-01 | 广东东阳光药业有限公司 | 取代的吲哚化合物及其使用方法和用途 |
| WO2015014256A1 (en) | 2013-07-29 | 2015-02-05 | Sunshine Lake Pharma Co., Ltd. | Substituted heteroaryl compounds and methods of use thereof |
| CN104725363B (zh) * | 2013-12-20 | 2019-03-01 | 广东东阳光药业有限公司 | 取代的哌嗪化合物及其使用方法和用途 |
| CN104725359B (zh) * | 2013-12-20 | 2017-05-03 | 广东东阳光药业有限公司 | 取代的哌嗪化合物及其使用方法和用途 |
| WO2016192657A1 (en) | 2015-06-03 | 2016-12-08 | Sunshine Lake Pharma Co., Ltd. | Substituted piperazine compounds and methods of use and use thereof |
| CN111386272B (zh) * | 2017-10-27 | 2023-01-06 | 费森尤斯卡比肿瘤学有限公司 | 一种改进的瑞博西尼及其盐的制备方法 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB944443A (en:Method) * | 1959-09-25 | 1900-01-01 | ||
| GB1189064A (en) | 1967-05-01 | 1970-04-22 | Sterling Drug Inc | Indole Derivatives |
| IT1170387B (it) | 1982-06-07 | 1987-06-03 | Glaxo Group Ltd | Composti eterociclici, procedimento per prepararli e composizioni farmaceutiche che li contengono |
| GB2162522B (en) | 1984-08-01 | 1988-02-24 | Glaxo Group Ltd | An indole derivative |
| US4954502A (en) * | 1988-06-10 | 1990-09-04 | Bristol-Myers Squibb Company | 1-indolyalkyl-4-(substituted-pyridinyl)piperazines |
| FR2635104B1 (fr) | 1988-08-03 | 1992-04-30 | Synthelabo | Derives d'indolone, leur preparation et leur application en therapeutique |
| GB8830312D0 (en) | 1988-12-28 | 1989-02-22 | Lundbeck & Co As H | Heterocyclic compounds |
| JP2871811B2 (ja) | 1990-02-28 | 1999-03-17 | サントリー株式会社 | 縮合７員環系化合物 |
| US5077293A (en) | 1990-06-29 | 1991-12-31 | Bristol-Myers Squibb Co. | 1-indolyalkyl-4-(alkoxypyrimidinyl)piperazines |
| CA2043709C (en) * | 1990-06-29 | 2002-01-22 | David W. Smith | Antimigraine alkoxypyrimidine derivatives |
-
1992
- 1992-12-04 CA CA002084531A patent/CA2084531A1/en not_active Abandoned
- 1992-12-07 CZ CS923592A patent/CZ359292A3/cs unknown
- 1992-12-08 IL IL104024A patent/IL104024A/xx not_active IP Right Cessation
- 1992-12-09 MX MX9207114A patent/MX9207114A/es unknown
- 1992-12-10 AU AU30034/92A patent/AU661527B2/en not_active Ceased
- 1992-12-10 NO NO924764A patent/NO302522B1/no unknown
- 1992-12-11 NZ NZ245439A patent/NZ245439A/xx unknown
- 1992-12-14 TW TW081110009A patent/TW221420B/zh active
- 1992-12-15 PH PH45427A patent/PH30988A/en unknown
- 1992-12-17 FI FI925737A patent/FI925737L/fi not_active Application Discontinuation
- 1992-12-17 RU RU92016241A patent/RU2114111C1/ru active
- 1992-12-17 EP EP92121519A patent/EP0548813A1/en not_active Ceased
- 1992-12-18 JP JP4361763A patent/JPH05262762A/ja active Pending
-
1993
- 1993-01-02 CN CN93101186A patent/CN1085556A/zh active Pending
-
1994
- 1994-04-26 US US08/233,545 patent/US5434154A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| NZ245439A (en) | 1995-07-26 |
| RU2114111C1 (ru) | 1998-06-27 |
| MX9207114A (es) | 1993-07-01 |
| CN1085556A (zh) | 1994-04-20 |
| NO924764L (no) | 1993-06-21 |
| EP0548813A1 (en) | 1993-06-30 |
| NO924764D0 (no) | 1992-12-10 |
| PH30988A (en) | 1997-12-23 |
| AU3003492A (en) | 1994-03-24 |
| TW221420B (en:Method) | 1994-03-01 |
| FI925737A7 (fi) | 1993-06-20 |
| FI925737A0 (fi) | 1992-12-17 |
| CA2084531A1 (en) | 1993-06-20 |
| US5434154A (en) | 1995-07-18 |
| NO302522B1 (no) | 1998-03-16 |
| IL104024A (en) | 1997-04-15 |
| AU661527B2 (en) | 1995-07-27 |
| JPH05262762A (ja) | 1993-10-12 |
| FI925737L (fi) | 1993-06-20 |
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