NO301225B1 - Indolderivater - Google Patents
Indolderivater Download PDFInfo
- Publication number
- NO301225B1 NO301225B1 NO941918A NO941918A NO301225B1 NO 301225 B1 NO301225 B1 NO 301225B1 NO 941918 A NO941918 A NO 941918A NO 941918 A NO941918 A NO 941918A NO 301225 B1 NO301225 B1 NO 301225B1
- Authority
- NO
- Norway
- Prior art keywords
- indole
- ylamino
- ylmethyl
- nitropyrid
- methylpyrrolidin
- Prior art date
Links
- 150000002475 indoles Chemical class 0.000 title description 4
- 229940054051 antipsychotic indole derivative Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 169
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 35
- 150000003839 salts Chemical class 0.000 claims abstract description 24
- 208000019695 Migraine disease Diseases 0.000 claims abstract description 15
- 206010027599 migraine Diseases 0.000 claims abstract description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 10
- 208000035475 disorder Diseases 0.000 claims abstract description 9
- 206010009094 Chronic paroxysmal hemicrania Diseases 0.000 claims abstract description 7
- 208000030814 Eating disease Diseases 0.000 claims abstract description 7
- 208000019454 Feeding and Eating disease Diseases 0.000 claims abstract description 7
- 206010019233 Headaches Diseases 0.000 claims abstract description 7
- 208000008589 Obesity Diseases 0.000 claims abstract description 7
- 208000002193 Pain Diseases 0.000 claims abstract description 7
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 7
- 235000014632 disordered eating Nutrition 0.000 claims abstract description 7
- 231100000869 headache Toxicity 0.000 claims abstract description 7
- 235000020824 obesity Nutrition 0.000 claims abstract description 7
- 208000007777 paroxysmal Hemicrania Diseases 0.000 claims abstract description 7
- 208000011117 substance-related disease Diseases 0.000 claims abstract description 7
- 208000006561 Cluster Headache Diseases 0.000 claims abstract description 6
- 206010013654 Drug abuse Diseases 0.000 claims abstract description 5
- 230000000862 serotonergic effect Effects 0.000 claims abstract description 5
- 230000005062 synaptic transmission Effects 0.000 claims abstract description 5
- 208000019553 vascular disease Diseases 0.000 claims abstract description 4
- 208000018912 cluster headache syndrome Diseases 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims description 53
- 238000002360 preparation method Methods 0.000 claims description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 239000001257 hydrogen Substances 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 7
- 206010029216 Nervousness Diseases 0.000 claims description 6
- 206010020772 Hypertension Diseases 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- QGSFFVWTEIOHEG-CYBMUJFWSA-N n-(3-nitropyridin-2-yl)-3-[[(2r)-pyrrolidin-2-yl]methyl]-1h-indol-5-amine Chemical compound [O-][N+](=O)C1=CC=CN=C1NC1=CC=C(NC=C2C[C@@H]3NCCC3)C2=C1 QGSFFVWTEIOHEG-CYBMUJFWSA-N 0.000 claims description 4
- XSYJQEZZWSZTPY-QGZVFWFLSA-N 3-[(2r)-2-[[5-[(3-nitropyridin-2-yl)amino]-1h-indol-3-yl]methyl]pyrrolidin-1-yl]propanenitrile Chemical compound [O-][N+](=O)C1=CC=CN=C1NC1=CC=C(NC=C2C[C@@H]3N(CCC3)CCC#N)C2=C1 XSYJQEZZWSZTPY-QGZVFWFLSA-N 0.000 claims description 3
- FDRXPJDDPRTYEV-UHFFFAOYSA-N 3-[2-(dimethylamino)ethyl]-n-(3-methylsulfonylpyridin-2-yl)-1h-indol-5-amine Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1NC1=NC=CC=C1S(C)(=O)=O FDRXPJDDPRTYEV-UHFFFAOYSA-N 0.000 claims description 3
- AZLDNTAMTOYQRB-UHFFFAOYSA-N 3-[2-(dimethylamino)ethyl]-n-[3-(trifluoromethyl)pyridin-2-yl]-1h-indol-5-amine Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1NC1=NC=CC=C1C(F)(F)F AZLDNTAMTOYQRB-UHFFFAOYSA-N 0.000 claims description 3
- LIOZXLCVRRJLCM-GOSISDBHSA-N 3-[[(2r)-1-(cyclopropylmethyl)pyrrolidin-2-yl]methyl]-n-(3-nitropyridin-2-yl)-1h-indol-5-amine Chemical compound [O-][N+](=O)C1=CC=CN=C1NC1=CC=C(NC=C2C[C@@H]3N(CCC3)CC3CC3)C2=C1 LIOZXLCVRRJLCM-GOSISDBHSA-N 0.000 claims description 3
- QGMOXXREEYLSJR-GOSISDBHSA-N 3-[[(2r)-1-butylpyrrolidin-2-yl]methyl]-n-(3-nitropyridin-2-yl)-1h-indol-5-amine Chemical compound CCCCN1CCC[C@@H]1CC(C1=C2)=CNC1=CC=C2NC1=NC=CC=C1[N+]([O-])=O QGMOXXREEYLSJR-GOSISDBHSA-N 0.000 claims description 3
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 3
- HUYZDGPJPIZBNZ-QGZVFWFLSA-N n-(3-nitropyridin-2-yl)-3-[[(2r)-1-propylpyrrolidin-2-yl]methyl]-1h-indol-5-amine Chemical compound CCCN1CCC[C@@H]1CC(C1=C2)=CNC1=CC=C2NC1=NC=CC=C1[N+]([O-])=O HUYZDGPJPIZBNZ-QGZVFWFLSA-N 0.000 claims description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- UVXRSGRIOMXXJE-QGZVFWFLSA-N 2-[[3-[[(2r)-1-methylpyrrolidin-2-yl]methyl]-1h-indol-5-yl]amino]pyridine-3-carbonitrile Chemical compound CN1CCC[C@@H]1CC(C1=C2)=CNC1=CC=C2NC1=NC=CC=C1C#N UVXRSGRIOMXXJE-QGZVFWFLSA-N 0.000 claims description 2
- BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 claims description 2
- PVXLQWOKNFBOMX-UHFFFAOYSA-N 3-[2-(dimethylamino)ethyl]-n-(3,5-dinitropyridin-2-yl)-1h-indol-5-amine Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1NC1=NC=C([N+]([O-])=O)C=C1[N+]([O-])=O PVXLQWOKNFBOMX-UHFFFAOYSA-N 0.000 claims description 2
- BKEYSQMZLXOXIZ-UHFFFAOYSA-N 3-[2-(dimethylamino)ethyl]-n-pyrimidin-2-yl-1h-indol-5-amine Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1NC1=NC=CC=N1 BKEYSQMZLXOXIZ-UHFFFAOYSA-N 0.000 claims description 2
- GJMASAFQMIHBSQ-MRXNPFEDSA-N 3-[[(2r)-1-ethylpyrrolidin-2-yl]methyl]-n-(3-nitropyridin-2-yl)-1h-indol-5-amine Chemical compound CCN1CCC[C@@H]1CC(C1=C2)=CNC1=CC=C2NC1=NC=CC=C1[N+]([O-])=O GJMASAFQMIHBSQ-MRXNPFEDSA-N 0.000 claims description 2
- VDZNDWMPUDOPAI-MRXNPFEDSA-N 3-[[(2r)-1-methylpyrrolidin-2-yl]methyl]-n-(2-nitrophenyl)-1h-indol-5-amine Chemical compound CN1CCC[C@@H]1CC(C1=C2)=CNC1=CC=C2NC1=CC=CC=C1[N+]([O-])=O VDZNDWMPUDOPAI-MRXNPFEDSA-N 0.000 claims description 2
- HEZAILYXZAPXJS-OAQYLSRUSA-N 3-[[(2r)-1-methylpyrrolidin-2-yl]methyl]-n-(3-nitro-5-phenylpyridin-2-yl)-1h-indol-5-amine Chemical compound CN1CCC[C@@H]1CC(C1=C2)=CNC1=CC=C2NC1=NC=C(C=2C=CC=CC=2)C=C1[N+]([O-])=O HEZAILYXZAPXJS-OAQYLSRUSA-N 0.000 claims description 2
- ACBVRTHXCIPQNJ-QGZVFWFLSA-N 3-[[(2r)-1-methylpyrrolidin-2-yl]methyl]-n-(3-nitro-6-propan-2-yloxypyridin-2-yl)-1h-indol-5-amine Chemical compound CC(C)OC1=CC=C([N+]([O-])=O)C(NC=2C=C3C(C[C@@H]4N(CCC4)C)=CNC3=CC=2)=N1 ACBVRTHXCIPQNJ-QGZVFWFLSA-N 0.000 claims description 2
- XJNSAOAOIJNZNJ-MRXNPFEDSA-N 3-[[(2r)-1-methylpyrrolidin-2-yl]methyl]-n-[2-nitro-4-(trifluoromethyl)phenyl]-1h-indol-5-amine Chemical compound CN1CCC[C@@H]1CC(C1=C2)=CNC1=CC=C2NC1=CC=C(C(F)(F)F)C=C1[N+]([O-])=O XJNSAOAOIJNZNJ-MRXNPFEDSA-N 0.000 claims description 2
- LCBGIPJZPBSJQD-QGZVFWFLSA-N 4-[[3-[[(2r)-1-methylpyrrolidin-2-yl]methyl]-1h-indol-5-yl]amino]-3-nitrobenzonitrile Chemical compound CN1CCC[C@@H]1CC(C1=C2)=CNC1=CC=C2NC1=CC=C(C#N)C=C1[N+]([O-])=O LCBGIPJZPBSJQD-QGZVFWFLSA-N 0.000 claims description 2
- ZZWTURMUQBOOOE-QZTJIDSGSA-N 4-[[3-[[(2r,4r)-4-methoxy-1-methylpyrrolidin-2-yl]methyl]-1h-indol-5-yl]amino]-3-nitrobenzonitrile Chemical compound CN1C[C@H](OC)C[C@H]1CC(C1=C2)=CNC1=CC=C2NC1=CC=C(C#N)C=C1[N+]([O-])=O ZZWTURMUQBOOOE-QZTJIDSGSA-N 0.000 claims description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 206010013663 drug dependence Diseases 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- HBEMHXITJQKCGA-CQSZACIVSA-N n-(2,3-dichloro-6-nitrophenyl)-3-[[(2r)-1-methylpyrrolidin-2-yl]methyl]-1h-indol-5-amine Chemical compound CN1CCC[C@@H]1CC(C1=C2)=CNC1=CC=C2NC1=C(Cl)C(Cl)=CC=C1[N+]([O-])=O HBEMHXITJQKCGA-CQSZACIVSA-N 0.000 claims description 2
- KHQZLDCXGGITFM-LJQANCHMSA-N n-(3-nitropyridin-2-yl)-3-[[(2r)-1-pentylpyrrolidin-2-yl]methyl]-1h-indol-5-amine Chemical compound CCCCCN1CCC[C@@H]1CC(C1=C2)=CNC1=CC=C2NC1=NC=CC=C1[N+]([O-])=O KHQZLDCXGGITFM-LJQANCHMSA-N 0.000 claims description 2
- GAEBPMGUDGBWMS-QGZVFWFLSA-N n-(3-nitropyridin-2-yl)-3-[[(2r)-1-prop-2-ynylpyrrolidin-2-yl]methyl]-1h-indol-5-amine Chemical compound [O-][N+](=O)C1=CC=CN=C1NC1=CC=C(NC=C2C[C@@H]3N(CCC3)CC#C)C2=C1 GAEBPMGUDGBWMS-QGZVFWFLSA-N 0.000 claims description 2
- ULWLGNGXNWPAKN-MRXNPFEDSA-N n-(4-methyl-3-nitropyridin-2-yl)-3-[[(2r)-1-methylpyrrolidin-2-yl]methyl]-1h-indol-5-amine Chemical compound CN1CCC[C@@H]1CC(C1=C2)=CNC1=CC=C2NC1=NC=CC(C)=C1[N+]([O-])=O ULWLGNGXNWPAKN-MRXNPFEDSA-N 0.000 claims description 2
- CPKHGURQECYECF-OAHLLOKOSA-N n-(6-methoxy-3-nitropyridin-2-yl)-3-[[(2r)-1-methylpyrrolidin-2-yl]methyl]-1h-indol-5-amine Chemical compound COC1=CC=C([N+]([O-])=O)C(NC=2C=C3C(C[C@@H]4N(CCC4)C)=CNC3=CC=2)=N1 CPKHGURQECYECF-OAHLLOKOSA-N 0.000 claims description 2
- WCFSAHRMJNVDJW-OAHLLOKOSA-N n-[3-[[(2r)-1-methylpyrrolidin-2-yl]methyl]-1h-indol-5-yl]-n-pyridin-2-ylnitramide Chemical compound CN1CCC[C@@H]1CC1=CNC2=CC=C(N(C=3N=CC=CC=3)[N+]([O-])=O)C=C12 WCFSAHRMJNVDJW-OAHLLOKOSA-N 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
- ZUWYPMSEUDQWNJ-QGZVFWFLSA-N 3-[[(2r)-1-(2-methoxyethyl)pyrrolidin-2-yl]methyl]-n-(3-nitropyridin-2-yl)-1h-indol-5-amine Chemical compound COCCN1CCC[C@@H]1CC(C1=C2)=CNC1=CC=C2NC1=NC=CC=C1[N+]([O-])=O ZUWYPMSEUDQWNJ-QGZVFWFLSA-N 0.000 claims 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- DKOWLCZKNFFWJR-QGZVFWFLSA-N n-(3-nitropyridin-2-yl)-3-[[(2r)-1-prop-2-enylpyrrolidin-2-yl]methyl]-1h-indol-5-amine Chemical compound [O-][N+](=O)C1=CC=CN=C1NC1=CC=C(NC=C2C[C@@H]3N(CCC3)CC=C)C2=C1 DKOWLCZKNFFWJR-QGZVFWFLSA-N 0.000 claims 1
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 abstract description 6
- 208000020401 Depressive disease Diseases 0.000 abstract description 2
- 239000000556 agonist Substances 0.000 abstract description 2
- 239000002220 antihypertensive agent Substances 0.000 abstract description 2
- 229940030600 antihypertensive agent Drugs 0.000 abstract description 2
- 229940076279 serotonin Drugs 0.000 abstract description 2
- 229940124549 vasodilator Drugs 0.000 abstract description 2
- 239000003071 vasodilator agent Substances 0.000 abstract description 2
- 208000019901 Anxiety disease Diseases 0.000 abstract 1
- 230000036506 anxiety Effects 0.000 abstract 1
- 230000002950 deficient Effects 0.000 abstract 1
- 230000003389 potentiating effect Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 116
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 90
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 86
- 238000005481 NMR spectroscopy Methods 0.000 description 79
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 72
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 71
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 62
- 239000002904 solvent Substances 0.000 description 59
- 239000002585 base Substances 0.000 description 54
- 239000007787 solid Substances 0.000 description 52
- 239000000243 solution Substances 0.000 description 51
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 50
- 238000006243 chemical reaction Methods 0.000 description 50
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 49
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 41
- 238000004458 analytical method Methods 0.000 description 36
- 239000011541 reaction mixture Substances 0.000 description 33
- 238000004587 chromatography analysis Methods 0.000 description 31
- 239000006260 foam Substances 0.000 description 31
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
- 238000010992 reflux Methods 0.000 description 25
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 24
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
- -1 N-piperidinyl Chemical group 0.000 description 21
- 238000004440 column chromatography Methods 0.000 description 20
- 238000000034 method Methods 0.000 description 19
- 239000003921 oil Substances 0.000 description 19
- 235000019198 oils Nutrition 0.000 description 19
- 239000000741 silica gel Substances 0.000 description 18
- 229910002027 silica gel Inorganic materials 0.000 description 18
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 18
- 229910001868 water Inorganic materials 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 239000002253 acid Substances 0.000 description 15
- KYXMPXCAXJDUTQ-UHFFFAOYSA-N 3-[2-(dimethylamino)ethyl]-1h-indol-5-amine Chemical compound C1=C(N)C=C2C(CCN(C)C)=CNC2=C1 KYXMPXCAXJDUTQ-UHFFFAOYSA-N 0.000 description 14
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 14
- 229960000583 acetic acid Drugs 0.000 description 14
- 239000002168 alkylating agent Substances 0.000 description 14
- 229940100198 alkylating agent Drugs 0.000 description 14
- 235000019441 ethanol Nutrition 0.000 description 14
- BBSNAHSUZJDFLE-GFCCVEGCSA-N 3-[[(2r)-1-methylpyrrolidin-2-yl]methyl]-1h-indol-5-amine Chemical compound CN1CCC[C@@H]1CC1=CNC2=CC=C(N)C=C12 BBSNAHSUZJDFLE-GFCCVEGCSA-N 0.000 description 13
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 13
- 239000000908 ammonium hydroxide Substances 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 238000001704 evaporation Methods 0.000 description 12
- 239000000284 extract Substances 0.000 description 12
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 12
- 239000012047 saturated solution Substances 0.000 description 12
- 230000008020 evaporation Effects 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical class C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 10
- 239000003153 chemical reaction reagent Substances 0.000 description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000007810 chemical reaction solvent Substances 0.000 description 9
- 229910000029 sodium carbonate Inorganic materials 0.000 description 9
- 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
- 239000010410 layer Substances 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- UUOLETYDNTVQDY-UHFFFAOYSA-N 2-chloro-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CN=C1Cl UUOLETYDNTVQDY-UHFFFAOYSA-N 0.000 description 7
- 150000007513 acids Chemical class 0.000 description 7
- ZCBIFHNDZBSCEP-UHFFFAOYSA-N 1H-indol-5-amine Chemical class NC1=CC=C2NC=CC2=C1 ZCBIFHNDZBSCEP-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000000443 aerosol Substances 0.000 description 6
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 6
- 238000000605 extraction Methods 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 239000012312 sodium hydride Substances 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 5
- 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 5
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- SEEYREPSKCQBBF-UHFFFAOYSA-N n-methylmaleimide Chemical compound CN1C(=O)C=CC1=O SEEYREPSKCQBBF-UHFFFAOYSA-N 0.000 description 1
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- 150000002825 nitriles Chemical class 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
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- 229920001592 potato starch Polymers 0.000 description 1
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- 239000003380 propellant Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical class CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 210000003752 saphenous vein Anatomy 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
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- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
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- 235000010356 sorbitol Nutrition 0.000 description 1
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- 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
- CWZNBQYCTVPBGJ-UHFFFAOYSA-N tert-butyl 4-(5-pyridin-2-yloxy-1h-indol-3-yl)-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC(C=2C3=CC(OC=4N=CC=CC=4)=CC=C3NC=2)=C1 CWZNBQYCTVPBGJ-UHFFFAOYSA-N 0.000 description 1
- NAULETSTCAIHFJ-UHFFFAOYSA-N tert-butyl 4-[5-(3-nitropyridin-2-yl)oxy-1h-indol-3-yl]-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC(C=2C3=CC(OC=4C(=CC=CN=4)[N+]([O-])=O)=CC=C3NC=2)=C1 NAULETSTCAIHFJ-UHFFFAOYSA-N 0.000 description 1
- SIVWCAPUGCRLDS-UHFFFAOYSA-N tert-butyl 4-[5-(pyridin-2-ylamino)-1h-indol-3-yl]-3,6-dihydro-2h-pyridine-1-carboxylate Chemical class C1N(C(=O)OC(C)(C)C)CCC(C=2C3=CC(NC=4N=CC=CC=4)=CC=C3NC=2)=C1 SIVWCAPUGCRLDS-UHFFFAOYSA-N 0.000 description 1
- ZLSWPESSEFZTMS-UHFFFAOYSA-N tert-butyl 4-[5-(pyridin-2-ylamino)-1h-indol-3-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C(C1=C2)=CNC1=CC=C2NC1=CC=CC=N1 ZLSWPESSEFZTMS-UHFFFAOYSA-N 0.000 description 1
- BVKVXFHWBCVAJD-UHFFFAOYSA-N tert-butyl 4-[5-[(3-nitropyridin-2-yl)amino]-1h-indol-3-yl]-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC(C=2C3=CC(NC=4C(=CC=CN=4)[N+]([O-])=O)=CC=C3NC=2)=C1 BVKVXFHWBCVAJD-UHFFFAOYSA-N 0.000 description 1
- IJBWBIOWUSVNOD-UHFFFAOYSA-N tert-butyl 4-[5-[(5-nitropyridin-2-yl)amino]-1h-indol-3-yl]-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC(C=2C3=CC(NC=4N=CC(=CC=4)[N+]([O-])=O)=CC=C3NC=2)=C1 IJBWBIOWUSVNOD-UHFFFAOYSA-N 0.000 description 1
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-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
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000005270 trialkylamine group Chemical group 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
- 230000002792 vascular Effects 0.000 description 1
Classifications
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- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
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- 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
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- 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
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- 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
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- 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
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Addiction (AREA)
- Child & Adolescent Psychology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Anesthesiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US79674491A | 1991-11-25 | 1991-11-25 | |
PCT/US1992/008306 WO1993011106A1 (en) | 1991-11-25 | 1992-10-06 | Indole derivatives |
Publications (3)
Publication Number | Publication Date |
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NO941918L NO941918L (no) | 1994-05-24 |
NO941918D0 NO941918D0 (no) | 1994-05-24 |
NO301225B1 true NO301225B1 (no) | 1997-09-29 |
Family
ID=25168947
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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NO941918A NO301225B1 (no) | 1991-11-25 | 1994-05-24 | Indolderivater |
Country Status (30)
Country | Link |
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US (1) | US5639752A (da) |
EP (1) | EP0619805B1 (da) |
JP (2) | JP2840448B2 (da) |
KR (1) | KR0184911B1 (da) |
CN (1) | CN1045294C (da) |
AT (1) | ATE190608T1 (da) |
AU (1) | AU671959B2 (da) |
BR (1) | BR9206810A (da) |
CA (1) | CA2124206C (da) |
CZ (1) | CZ281874B6 (da) |
DE (1) | DE69230803T2 (da) |
DK (1) | DK0619805T3 (da) |
EG (1) | EG21209A (da) |
ES (1) | ES2143992T3 (da) |
FI (1) | FI942395A (da) |
GR (1) | GR3033370T3 (da) |
HU (1) | HUT69705A (da) |
IL (1) | IL103798A (da) |
MX (1) | MX9206762A (da) |
MY (1) | MY109954A (da) |
NO (1) | NO301225B1 (da) |
NZ (2) | NZ272130A (da) |
PL (1) | PL173875B1 (da) |
PT (1) | PT101087B (da) |
RU (1) | RU2126399C1 (da) |
TW (1) | TW229205B (da) |
UA (1) | UA41297C2 (da) |
WO (1) | WO1993011106A1 (da) |
YU (1) | YU48456B (da) |
ZA (1) | ZA929082B (da) |
Families Citing this family (66)
Publication number | Priority date | Publication date | Assignee | Title |
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US5607951A (en) * | 1990-10-15 | 1997-03-04 | Pfizer Inc | Indole derivatives |
US5559129A (en) * | 1990-10-15 | 1996-09-24 | Pfizer Inc | Indole derivatives |
US5559246A (en) * | 1990-10-15 | 1996-09-24 | Pfizer Inc. | Indole derivatives |
US5545644A (en) * | 1990-10-15 | 1996-08-13 | Pfizer Inc. | Indole derivatives |
US5578612A (en) * | 1990-10-15 | 1996-11-26 | Pfizer Inc. | Indole derivatives |
UA41297C2 (uk) * | 1991-11-25 | 2001-09-17 | Пфайзер, Інк. | Похідні індолу, фармацевтична композиція і спосіб лікування |
GB9207396D0 (en) * | 1992-04-03 | 1992-05-13 | Merck Sharp & Dohme | Therapeutic agents |
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