BG62024B2 - Производни на имидазол,триазол и тетразол - Google Patents
Производни на имидазол,триазол и тетразол Download PDFInfo
- Publication number
- BG62024B2 BG62024B2 BG097943A BG9794393A BG62024B2 BG 62024 B2 BG62024 B2 BG 62024B2 BG 097943 A BG097943 A BG 097943A BG 9794393 A BG9794393 A BG 9794393A BG 62024 B2 BG62024 B2 BG 62024B2
- Authority
- BG
- Bulgaria
- Prior art keywords
- formula
- indol
- methyl
- ethylamine
- group
- Prior art date
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- 150000003536 tetrazoles Chemical class 0.000 title claims description 15
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 title description 17
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical class ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 175
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 81
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 67
- 239000000203 mixture Substances 0.000 claims abstract description 57
- 238000000034 method Methods 0.000 claims abstract description 48
- 150000003839 salts Chemical class 0.000 claims abstract description 48
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 46
- 239000001257 hydrogen Substances 0.000 claims abstract description 42
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 25
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 17
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 16
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 15
- 238000011282 treatment Methods 0.000 claims abstract description 14
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 13
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000001301 oxygen Substances 0.000 claims abstract description 13
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 13
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 11
- 239000000126 substance Substances 0.000 claims abstract description 5
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 4
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims description 87
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 39
- -1 N, N-dimethylamino Chemical group 0.000 claims description 35
- 238000006243 chemical reaction Methods 0.000 claims description 20
- 239000000651 prodrug Substances 0.000 claims description 16
- 229940002612 prodrug Drugs 0.000 claims description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 13
- 239000002253 acid Substances 0.000 claims description 12
- 239000011593 sulfur Chemical group 0.000 claims description 12
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 10
- 239000002243 precursor Substances 0.000 claims description 10
- 239000003153 chemical reaction reagent Substances 0.000 claims description 9
- 125000004122 cyclic group Chemical group 0.000 claims description 9
- 238000010561 standard procedure Methods 0.000 claims description 9
- 208000019695 Migraine disease Diseases 0.000 claims description 8
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 8
- 150000001450 anions Chemical class 0.000 claims description 8
- 238000005859 coupling reaction Methods 0.000 claims description 8
- LOTBYPQQWICYBB-UHFFFAOYSA-N methyl n-hexyl-n-[2-(hexylamino)ethyl]carbamate Chemical compound CCCCCCNCCN(C(=O)OC)CCCCCC LOTBYPQQWICYBB-UHFFFAOYSA-N 0.000 claims description 8
- VRESBNUEIKZECD-UHFFFAOYSA-N 2-methyltetrazole Chemical compound CN1N=CN=N1 VRESBNUEIKZECD-UHFFFAOYSA-N 0.000 claims description 7
- 150000001558 benzoic acid derivatives Chemical class 0.000 claims description 7
- 238000007363 ring formation reaction Methods 0.000 claims description 7
- 238000007126 N-alkylation reaction Methods 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 206010027599 migraine Diseases 0.000 claims description 6
- QKKBFEMDJATWTO-UHFFFAOYSA-N 2-[5-(1-methyltetrazol-5-yl)-1-benzothiophen-3-yl]ethanamine Chemical compound CN1N=NN=C1C1=CC=C(SC=C2CCN)C2=C1 QKKBFEMDJATWTO-UHFFFAOYSA-N 0.000 claims description 5
- 150000001540 azides Chemical class 0.000 claims description 5
- 230000008878 coupling Effects 0.000 claims description 5
- 238000010168 coupling process Methods 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 150000002825 nitriles Chemical class 0.000 claims description 5
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 4
- FBZMSEGNXHUXEL-UHFFFAOYSA-N 5-imidazol-1-yl-3-(1-methylpiperidin-4-yl)-1h-indole Chemical compound C1CN(C)CCC1C1=CNC2=CC=C(N3C=NC=C3)C=C12 FBZMSEGNXHUXEL-UHFFFAOYSA-N 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 238000007796 conventional method Methods 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- ULFRLSNUDGIQQP-UHFFFAOYSA-N rizatriptan Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CN1C=NC=N1 ULFRLSNUDGIQQP-UHFFFAOYSA-N 0.000 claims description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 4
- AQBHAXPSOCMLGV-UHFFFAOYSA-N 1-benzyltetrazole Chemical compound C1=NN=NN1CC1=CC=CC=C1 AQBHAXPSOCMLGV-UHFFFAOYSA-N 0.000 claims description 3
- OMAFFHIGWTVZOH-UHFFFAOYSA-N 1-methyltetrazole Chemical compound CN1C=NN=N1 OMAFFHIGWTVZOH-UHFFFAOYSA-N 0.000 claims description 3
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 3
- QSLJOIOPNUQETJ-UHFFFAOYSA-N 2-benzyltetrazole Chemical compound N1=CN=NN1CC1=CC=CC=C1 QSLJOIOPNUQETJ-UHFFFAOYSA-N 0.000 claims description 3
- FXEYJBOULOCKEQ-UHFFFAOYSA-N 3-(1-methylpyrrolidin-3-yl)-5-(triazol-1-yl)-1h-indole Chemical compound C1N(C)CCC1C1=CNC2=CC=C(N3N=NC=C3)C=C12 FXEYJBOULOCKEQ-UHFFFAOYSA-N 0.000 claims description 3
- YONMBTLKVAFELY-UHFFFAOYSA-N 5-(imidazol-1-ylmethyl)-3-(1-methylpyrrolidin-3-yl)-1h-indole Chemical compound C1N(C)CCC1C(C1=C2)=CNC1=CC=C2CN1C=NC=C1 YONMBTLKVAFELY-UHFFFAOYSA-N 0.000 claims description 3
- 239000000018 receptor agonist Substances 0.000 claims description 3
- 229940044601 receptor agonist Drugs 0.000 claims description 3
- HKLWYQXJOKBZMP-UHFFFAOYSA-N 3-(1-methylpiperidin-4-yl)-5-(triazol-1-yl)-1h-indole Chemical compound C1CN(C)CCC1C1=CNC2=CC=C(N3N=NC=C3)C=C12 HKLWYQXJOKBZMP-UHFFFAOYSA-N 0.000 claims description 2
- DFYZFBMGSKYHME-UHFFFAOYSA-N 3-piperidin-4-yl-5-(1,2,4-triazol-1-ylmethyl)-1h-indole Chemical compound C1=NC=NN1CC(C=C12)=CC=C1NC=C2C1CCNCC1 DFYZFBMGSKYHME-UHFFFAOYSA-N 0.000 claims description 2
- FYBVZGXVZMTVIE-UHFFFAOYSA-N 3-piperidin-4-yl-5-(triazol-1-yl)-1h-indole Chemical compound C1CNCCC1C1=CNC2=CC=C(N3N=NC=C3)C=C12 FYBVZGXVZMTVIE-UHFFFAOYSA-N 0.000 claims description 2
- KYIODCARUJLFDB-UHFFFAOYSA-N 5-(2-methylimidazol-1-yl)-3-(1-methylpyrrolidin-3-yl)-1h-indole Chemical compound C1N(C)CCC1C1=CNC2=CC=C(N3C(=NC=C3)C)C=C12 KYIODCARUJLFDB-UHFFFAOYSA-N 0.000 claims description 2
- XVYMQGIMVTXENU-UHFFFAOYSA-N 5-(2-methylimidazol-1-yl)-3-pyrrolidin-3-yl-1h-indole Chemical compound CC1=NC=CN1C1=CC=C(NC=C2C3CNCC3)C2=C1 XVYMQGIMVTXENU-UHFFFAOYSA-N 0.000 claims description 2
- APIXMXZTJADEDX-UHFFFAOYSA-N 5-[(2-methylimidazol-1-yl)methyl]-3-(1-methylpyrrolidin-3-yl)-1h-indole Chemical compound C1N(C)CCC1C(C1=C2)=CNC1=CC=C2CN1C(C)=NC=C1 APIXMXZTJADEDX-UHFFFAOYSA-N 0.000 claims description 2
- NTUFXJLPBBTZGI-UHFFFAOYSA-N 5-imidazol-1-yl-3-(1-methylpyrrolidin-3-yl)-1h-indole Chemical compound C1N(C)CCC1C1=CNC2=CC=C(N3C=NC=C3)C=C12 NTUFXJLPBBTZGI-UHFFFAOYSA-N 0.000 claims description 2
- 150000001345 alkine derivatives Chemical class 0.000 claims description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
- 239000011707 mineral Substances 0.000 claims description 2
- CCDMZRADLKWXMG-UHFFFAOYSA-N n,n-dimethyl-2-[5-(tetrazol-2-ylmethyl)-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CN1N=CN=N1 CCDMZRADLKWXMG-UHFFFAOYSA-N 0.000 claims description 2
- HTVLSIBBGWEXCH-UHFFFAOYSA-N n-methyl-2-[5-(1,2,4-triazol-1-ylmethyl)-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCNC)=CNC2=CC=C1CN1C=NC=N1 HTVLSIBBGWEXCH-UHFFFAOYSA-N 0.000 claims description 2
- 230000020477 pH reduction Effects 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims 3
- 238000004519 manufacturing process Methods 0.000 claims 3
- XREUBNCIWSUNOZ-UHFFFAOYSA-N 3-(1-methylpyrrolidin-3-yl)-5-(1,2,4-triazol-1-ylmethyl)-1h-indole Chemical compound C1N(C)CCC1C(C1=C2)=CNC1=CC=C2CN1N=CN=C1 XREUBNCIWSUNOZ-UHFFFAOYSA-N 0.000 claims 1
- VVHSUMPWKQTQLY-UHFFFAOYSA-N 5-(2-methylimidazol-1-yl)-3-piperidin-4-yl-1h-indole Chemical compound CC1=NC=CN1C1=CC=C(NC=C2C3CCNCC3)C2=C1 VVHSUMPWKQTQLY-UHFFFAOYSA-N 0.000 claims 1
- BFBSTHDZPIXCBB-UHFFFAOYSA-N 5-imidazol-1-yl-3-piperidin-4-yl-1h-indole Chemical compound C1CNCCC1C1=CNC2=CC=C(N3C=NC=C3)C=C12 BFBSTHDZPIXCBB-UHFFFAOYSA-N 0.000 claims 1
- 150000001735 carboxylic acids Chemical class 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 abstract description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
- 239000005864 Sulphur Chemical group 0.000 abstract 1
- 239000005557 antagonist Substances 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 145
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 69
- 239000000243 solution Substances 0.000 description 68
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 61
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 45
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 30
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- 239000000741 silica gel Substances 0.000 description 28
- 229910002027 silica gel Inorganic materials 0.000 description 28
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
- 239000000460 chlorine Substances 0.000 description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 239000007787 solid Substances 0.000 description 24
- 239000002904 solvent Substances 0.000 description 23
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- 235000019439 ethyl acetate Nutrition 0.000 description 21
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 239000000284 extract Substances 0.000 description 14
- 150000003891 oxalate salts Chemical class 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- 239000003826 tablet Substances 0.000 description 13
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 11
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- 239000011734 sodium Substances 0.000 description 10
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
- APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical class C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 9
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 8
- 150000003852 triazoles Chemical class 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 7
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 6
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 6
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 6
- 150000002828 nitro derivatives Chemical class 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- FLBZZWJMNUTZIP-UHFFFAOYSA-N 2-(1-benzylpyrrolidin-3-yl)acetaldehyde Chemical compound C1C(CC=O)CCN1CC1=CC=CC=C1 FLBZZWJMNUTZIP-UHFFFAOYSA-N 0.000 description 5
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 5
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 239000000556 agonist Substances 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 4
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical class C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- 229920002261 Corn starch Polymers 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 150000001448 anilines Chemical class 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000008120 corn starch Substances 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 235000006408 oxalic acid Nutrition 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 235000010288 sodium nitrite Nutrition 0.000 description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- WFQDTOYDVUWQMS-UHFFFAOYSA-N 1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1 WFQDTOYDVUWQMS-UHFFFAOYSA-N 0.000 description 3
- MHGRPEADXUSKAT-UHFFFAOYSA-N 2-(1-benzylpiperidin-4-yl)acetaldehyde Chemical compound C1CC(CC=O)CCN1CC1=CC=CC=C1 MHGRPEADXUSKAT-UHFFFAOYSA-N 0.000 description 3
- RLBGFQHGJXQUKY-UHFFFAOYSA-N 2-(1-methylpiperidin-4-yl)acetaldehyde Chemical compound CN1CCC(CC=O)CC1 RLBGFQHGJXQUKY-UHFFFAOYSA-N 0.000 description 3
- CGXFQHOURRTVKH-UHFFFAOYSA-N 2-[(4-nitrophenyl)methyl]-1h-imidazole Chemical compound C1=CC([N+](=O)[O-])=CC=C1CC1=NC=CN1 CGXFQHOURRTVKH-UHFFFAOYSA-N 0.000 description 3
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 210000003752 saphenous vein Anatomy 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 150000003334 secondary amides Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 150000003385 sodium Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- MDUSUFIKBUMDTJ-UHFFFAOYSA-N sodium;1h-1,2,4-triazole Chemical compound [Na].C=1N=CNN=1 MDUSUFIKBUMDTJ-UHFFFAOYSA-N 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
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- 239000005720 sucrose Substances 0.000 description 1
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- 239000000375 suspending agent Substances 0.000 description 1
- 239000000057 synthetic resin Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- QHOQMOHZAOPDKI-UHFFFAOYSA-N tert-butyl n-[2-[5-[(1-methyltetrazol-5-yl)methyl]-1h-indol-3-yl]ethyl]carbamate Chemical compound CN1N=NN=C1CC1=CC=C(NC=C2CCNC(=O)OC(C)(C)C)C2=C1 QHOQMOHZAOPDKI-UHFFFAOYSA-N 0.000 description 1
- RQTCJHDGGIFABL-UHFFFAOYSA-N tert-butyl n-[2-[5-[(2-nitroimidazol-1-yl)methyl]-1h-indol-3-yl]ethyl]carbamate Chemical compound C1=C2C(CCNC(=O)OC(C)(C)C)=CNC2=CC=C1CN1C=CN=C1[N+]([O-])=O RQTCJHDGGIFABL-UHFFFAOYSA-N 0.000 description 1
- JTJZBWZZVWYJMF-UHFFFAOYSA-N tert-butyl n-[2-[5-[(dimethylamino)methyl]-1h-indol-3-yl]ethyl]carbamate Chemical compound CN(C)CC1=CC=C2NC=C(CCNC(=O)OC(C)(C)C)C2=C1 JTJZBWZZVWYJMF-UHFFFAOYSA-N 0.000 description 1
- 150000003511 tertiary amides Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 150000007970 thio esters Chemical class 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
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 238000010792 warming Methods 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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- 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
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- 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
- C07D401/14—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 three or more hetero rings
-
- 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
- C07D403/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D403/06—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 carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D403/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Neurosurgery (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pain & Pain Management (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Epoxy Resins (AREA)
- Paints Or Removers (AREA)
- Lubricants (AREA)
- Adhesives Or Adhesive Processes (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Photoreceptors In Electrophotography (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Dental Preparations (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB919102222A GB9102222D0 (en) | 1991-02-01 | 1991-02-01 | Therapeutic agents |
| GB919106917A GB9106917D0 (en) | 1991-04-03 | 1991-04-03 | Therapeutic agents |
| GB919113415A GB9113415D0 (en) | 1991-06-21 | 1991-06-21 | Therapeutic agents |
| GB919122451A GB9122451D0 (en) | 1991-10-23 | 1991-10-23 | Therapeutic agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BG62024B2 true BG62024B2 (bg) | 1998-12-30 |
Family
ID=27450619
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BG097943A BG62024B2 (bg) | 1991-02-01 | 1993-07-14 | Производни на имидазол,триазол и тетразол |
Country Status (30)
| Country | Link |
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| US (4) | US5298520A (cs) |
| EP (2) | EP0778275B1 (cs) |
| JP (1) | JP2500280B2 (cs) |
| KR (1) | KR100212111B1 (cs) |
| CN (4) | CN1038681C (cs) |
| AT (1) | ATE158582T1 (cs) |
| BG (1) | BG62024B2 (cs) |
| CA (2) | CA2238140C (cs) |
| CY (1) | CY2095B1 (cs) |
| CZ (1) | CZ283018B6 (cs) |
| DE (2) | DE69222329T2 (cs) |
| DK (1) | DK0497512T3 (cs) |
| ES (2) | ES2106822T3 (cs) |
| FI (1) | FI107154B (cs) |
| GR (2) | GR3025026T3 (cs) |
| HR (1) | HRP930777B1 (cs) |
| HU (2) | HU222350B1 (cs) |
| IE (1) | IE920342A1 (cs) |
| IL (1) | IL100756A (cs) |
| LU (1) | LU90338I2 (cs) |
| LV (1) | LV12090B (cs) |
| MX (1) | MX9200405A (cs) |
| NL (1) | NL980019I1 (cs) |
| NO (2) | NO180447C (cs) |
| NZ (1) | NZ241394A (cs) |
| SA (1) | SA94140534B1 (cs) |
| SG (1) | SG50409A1 (cs) |
| SI (1) | SI9210101B (cs) |
| SK (1) | SK278998B6 (cs) |
| YU (1) | YU48236B (cs) |
Families Citing this family (123)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU646871B2 (en) * | 1990-06-07 | 1994-03-10 | Astrazeneca Uk Limited | Therapeutic heterocyclic compounds |
| US5559129A (en) * | 1990-10-15 | 1996-09-24 | Pfizer Inc | Indole derivatives |
| US5545644A (en) * | 1990-10-15 | 1996-08-13 | Pfizer Inc. | Indole derivatives |
| US5607951A (en) * | 1990-10-15 | 1997-03-04 | Pfizer Inc | Indole derivatives |
| US5559246A (en) * | 1990-10-15 | 1996-09-24 | Pfizer Inc. | Indole derivatives |
| US5578612A (en) * | 1990-10-15 | 1996-11-26 | Pfizer Inc. | Indole derivatives |
| EP0596933A1 (en) * | 1991-08-03 | 1994-05-18 | Smithkline Beecham Plc | 5-ht4 receptor antagonists |
| GB9201038D0 (en) * | 1992-01-16 | 1992-03-11 | Glaxo Group Ltd | Chemical compounds |
| TW288010B (cs) * | 1992-03-05 | 1996-10-11 | Pfizer | |
| AU669160B2 (en) * | 1992-03-13 | 1996-05-30 | Merck Sharp & Dohme Limited | Imidazole, triazole and tetrazole derivatives |
| GB9207396D0 (en) * | 1992-04-03 | 1992-05-13 | Merck Sharp & Dohme | Therapeutic agents |
| BR9306201A (pt) * | 1992-04-07 | 1998-06-23 | Pfizer | Derivados de indol como agonistas 5-ht1 |
| US6380233B1 (en) | 1992-04-07 | 2002-04-30 | Pfizer Inc | Indole derivatives as 5-HT1 agonists |
| GB9207930D0 (en) * | 1992-04-10 | 1992-05-27 | Pfizer Ltd | Indoles |
| ATE148465T1 (de) * | 1992-04-10 | 1997-02-15 | Pfizer | Acylaminoindolderivate als 5-ht1 agonisten |
| GB9208463D0 (en) * | 1992-04-16 | 1992-06-03 | Merck Sharp & Dohme | Therapeutic agents |
| GB9210400D0 (en) * | 1992-05-15 | 1992-07-01 | Merck Sharp & Dohme | Therapeutic agents |
| GB9211277D0 (en) | 1992-05-28 | 1992-07-15 | Glaxo Group Inc | Pharmaceutical compositions |
| AU659311B2 (en) * | 1992-06-05 | 1995-05-11 | Merck Sharp & Dohme Limited | The sulphate salt of a substituted triazole, pharmaceutical compositions thereof, and their use in therapy |
| GB9215526D0 (en) * | 1992-07-22 | 1992-09-02 | Merck Sharp & Dohme | Chemical process |
| AU672802B2 (en) * | 1992-07-24 | 1996-10-17 | Merck Sharp & Dohme Limited | Imidazole, triazole and tetrazole derivatives |
| 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 |
| TW251284B (cs) * | 1992-11-02 | 1995-07-11 | Pfizer | |
| GB9226537D0 (en) * | 1992-12-21 | 1993-02-17 | Smithkline Beecham Plc | Compounds |
| FR2701026B1 (fr) * | 1993-02-02 | 1995-03-31 | Adir | Nouveaux dérivés de l'indole, de l'indazole et du benzisoxazole, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent. |
| US6060473A (en) * | 1993-04-01 | 2000-05-09 | Ucb S.A. - Dtb | 7-azabicyclo[2.2.1]-heptane and -heptene derivatives as cholinergic receptor ligands |
| US5817679A (en) | 1993-04-01 | 1998-10-06 | University Of Virginia | 7-Azabicyclo 2.2.1!-heptane and -heptene derivatives as cholinergic receptor ligands |
| EP0716649B1 (en) * | 1993-08-31 | 1998-09-09 | Pfizer Inc. | 5-arylindole derivatives |
| WO1995007078A1 (en) * | 1993-09-10 | 1995-03-16 | Cytomed, Inc. | Epibatidine and derivatives thereof as cholinergic receptor agonists and antagonists |
| GB9402011D0 (en) * | 1994-02-02 | 1994-03-30 | Merck Sharp & Dohme | Therapeutic agents |
| GB9402016D0 (en) * | 1994-02-02 | 1994-03-30 | Merck Sharp & Dohme | Therapeutic agents |
| US6117889A (en) * | 1994-04-01 | 2000-09-12 | University Of Virginia | 7-Azabicyclo-[2.2.1]-heptane and -heptene derivatives as analgesics and anti-inflammatory agents |
| US5552402A (en) * | 1994-05-19 | 1996-09-03 | Merck, Sharp & Dohme Ltd. | Five-membered heteroaromatic compounds as 5-HT receptor agonists |
| GB9410031D0 (en) * | 1994-05-19 | 1994-07-06 | Merck Sharp & Dohme | Therapeutic agents |
| AU694226B2 (en) * | 1994-05-19 | 1998-07-16 | Merck Sharp & Dohme Limited | Piperazine, piperidine and tetrahydropyridine derivatives ofindol-3-ylalkyl as 5-HT1D-alpha agonists |
| US5567824A (en) * | 1994-05-24 | 1996-10-22 | Merck & Co., Inc. | Palladium catalyzed ring closure of triazolyltryptamine |
| MX9700693A (es) * | 1994-07-26 | 1997-04-30 | Pfizer | Derivados del 4-indol. |
| US5854268A (en) * | 1994-08-02 | 1998-12-29 | Merck Sharp & Dohme, Ltd. | Azetidine, pyrrolidine and piperidine derivatives |
| GB9417310D0 (en) | 1994-08-27 | 1994-10-19 | Pfizer Ltd | Therapeutic agents |
| US5521196A (en) * | 1994-10-05 | 1996-05-28 | Eli Lilly And Company | 5-HT1F agonists for the treatment of migraine |
| GB9423460D0 (en) * | 1994-11-21 | 1995-01-11 | Merck Sharp & Dohme | Therapeutic agents |
| US5521197A (en) * | 1994-12-01 | 1996-05-28 | Eli Lilly And Company | 3-<1-alkylenearyl>-4-<1,2,3,6-tetrahydropyridinyl>-and 3-<1-alkylenearyl>-4-piperidinyl-1h-indoles: new 5-HT1F agonists |
| GB9501865D0 (en) * | 1995-01-31 | 1995-03-22 | Merck Sharp & Dohme | Therapeutic agents |
| US5484763A (en) * | 1995-02-10 | 1996-01-16 | American Cyanamid Company | Substituted benzisoxazole and benzisothiazole herbicidal agents |
| CZ288897A3 (cs) * | 1995-03-20 | 1998-02-18 | Eli Lilly And Company | V poloze 5-substituovaný 3-(1,2,3,6-tetrahydropyridin-4-yl)indol a 3-(piperidin-4-yl)indol a farmaceutický prostředek, který je obsahuje |
| US6245768B1 (en) | 1995-06-05 | 2001-06-12 | Neurogen Corporation | 1-(N′-(arylalkylaminoalkyl)) aminoisoindoles; a new class of dopamine receptor subtype specific ligands |
| US5602168A (en) * | 1995-07-10 | 1997-02-11 | Neurogen Corporation | 1-(N'-(arylalkylaminoalkyl)) aminoisoindoles; dopamine receptor subtype specific ligands |
| US5656632A (en) * | 1995-06-05 | 1997-08-12 | Neurogen Corporation | 1-(N'-(arylalkylaminoalkyl)) aminoisoindoles; dopamine receptor subtype specific ligands |
| ZA965837B (en) * | 1995-07-11 | 1997-01-31 | Merck & Co Inc | A triazolylmethyl-indole ethylamine bisulfate salt |
| JPH11508916A (ja) * | 1995-07-11 | 1999-08-03 | メルク エンド カンパニー インコーポレーテッド | トリアゾリルメチル−インドールエチルアミン重硫酸塩 |
| CA2234166A1 (en) * | 1995-10-10 | 1997-04-17 | Patric James Hahn | N-¬2-substituted-3-(2-aminoethyl)-1h-indol-5-yl|-amides: new 5-ht1f agonists |
| US5998415A (en) * | 1995-11-02 | 1999-12-07 | Merck Sharp & Dohme Ltd. | Bicyclic heteroaryl-alkylene-(homo)piperazinones and thione analogues thereof, their preparation, and their use of as selective agonists of 5-HT1 -like receptors |
| GB9523583D0 (en) * | 1995-11-17 | 1996-01-17 | Merck Sharp & Dohme | Therapeutic agents |
| GB9610978D0 (en) * | 1996-05-24 | 1996-07-31 | Merck Sharp & Dohme | Therapeutic agents |
| US5877329A (en) * | 1996-08-13 | 1999-03-02 | Merck & Co., Inc. | Palladium catalyzed indolization |
| US5808064A (en) * | 1996-08-13 | 1998-09-15 | Merck & Co., Inc. | Palladium catalyzed indolization |
| US5811551A (en) * | 1996-08-13 | 1998-09-22 | Merck & Co., Inc. | Palladium catalyzed indolization |
| KR100494189B1 (ko) | 1996-08-19 | 2005-06-10 | 폭스바겐 악티엔 게젤샤프트 | ＮＯｘ 흡착기 |
| WO1998007497A1 (de) | 1996-08-19 | 1998-02-26 | Volkswagen Aktiengesellschaft | FREMDGEZÜNDETE BRENNKRAFTMASCHINE MIT EINEM NOx-ADSORBER |
| GB9620777D0 (en) * | 1996-10-07 | 1996-11-20 | Merck Sharp & Dohme | Therapeutic use |
| US5998438A (en) * | 1996-11-26 | 1999-12-07 | Allelix Biopharmaceuticals, Inc. | 5-cyclo indole compounds |
| US6066092A (en) * | 1997-11-06 | 2000-05-23 | Cady; Roger K. | Preemptive prophylaxis of migraine device and method |
| US7189753B1 (en) | 1997-11-06 | 2007-03-13 | Cady Roger K | Preemptive prophylaxis of migraine |
| DK1068198T3 (da) * | 1998-03-09 | 2003-09-22 | Lundbeck & Co As H | 5-Heteroarylsubstituerede indoler |
| EP1126841B1 (en) * | 1998-11-02 | 2004-12-15 | Merck & Co., Inc. | Combinations of a 5ht1b/1d agonist and a selective cox-2 inhibitor for the treatment of migraine |
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