DE2148553A1 - Verfahren zur Herstellung neuer heterocyclischer Verbindungen - Google Patents
Verfahren zur Herstellung neuer heterocyclischer VerbindungenInfo
- Publication number
- DE2148553A1 DE2148553A1 DE19712148553 DE2148553A DE2148553A1 DE 2148553 A1 DE2148553 A1 DE 2148553A1 DE 19712148553 DE19712148553 DE 19712148553 DE 2148553 A DE2148553 A DE 2148553A DE 2148553 A1 DE2148553 A1 DE 2148553A1
- Authority
- DE
- Germany
- Prior art keywords
- indole
- isopropylaminopropoxy
- methyl
- lower alkyl
- compounds
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 238000000034 method Methods 0.000 title claims description 60
- 238000002360 preparation method Methods 0.000 title description 11
- 150000002391 heterocyclic compounds Chemical class 0.000 title description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 118
- -1 1,1-dimethyl-2-propynyl Chemical group 0.000 claims description 65
- 150000001875 compounds Chemical class 0.000 claims description 63
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 60
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 60
- 125000000217 alkyl group Chemical group 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 7
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000004965 chloroalkyl group Chemical group 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- XMSZANIMCDLNKA-UHFFFAOYSA-N methyl hypofluorite Chemical compound COF XMSZANIMCDLNKA-UHFFFAOYSA-N 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 4
- 150000003254 radicals Chemical class 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- LWQXBMLVKURUQA-UHFFFAOYSA-N [1-(1H-indol-4-yloxy)-3-(propan-2-ylamino)propan-2-yl] 1-methylcyclohexane-1-carboxylate Chemical compound C(C)(C)NCC(COC1=C2C=CNC2=CC=C1)OC(=O)C1(CCCCC1)C LWQXBMLVKURUQA-UHFFFAOYSA-N 0.000 claims description 2
- GHHHRZXUOQJZEP-UHFFFAOYSA-N [1-(1H-indol-4-yloxy)-3-(propan-2-ylamino)propan-2-yl] heptanoate Chemical compound C(CCCCCC)(=O)OC(COC1=C2C=CNC2=CC=C1)CNC(C)C GHHHRZXUOQJZEP-UHFFFAOYSA-N 0.000 claims description 2
- 239000012458 free base Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- RMRFFCXPLWYOOY-UHFFFAOYSA-N allyl radical Chemical compound [CH2]C=C RMRFFCXPLWYOOY-UHFFFAOYSA-N 0.000 claims 2
- LGAOAHWMJNFDJX-UHFFFAOYSA-N [1-(1H-indol-4-yloxy)-3-(propan-2-ylamino)propan-2-yl] 2-methylpropanoate Chemical compound C(C(C)C)(=O)OC(COC1=C2C=CNC2=CC=C1)CNC(C)C LGAOAHWMJNFDJX-UHFFFAOYSA-N 0.000 claims 1
- WKXOSALBLWLBSO-UHFFFAOYSA-N [1-(1H-indol-4-yloxy)-3-(propan-2-ylamino)propan-2-yl] benzoate Chemical compound C(C1=CC=CC=C1)(=O)OC(COC1=C2C=CNC2=CC=C1)CNC(C)C WKXOSALBLWLBSO-UHFFFAOYSA-N 0.000 claims 1
- SGWQXISZWUQRLK-UHFFFAOYSA-N [1-(1H-indol-4-yloxy)-3-(propan-2-ylamino)propan-2-yl] cyclohexanecarboxylate Chemical compound C1(CCCCC1)C(=O)OC(COC1=C2C=CNC2=CC=C1)CNC(C)C SGWQXISZWUQRLK-UHFFFAOYSA-N 0.000 claims 1
- 229940126601 medicinal product Drugs 0.000 claims 1
- AFCCDDWKHLHPDF-UHFFFAOYSA-M metam-sodium Chemical compound [Na+].CNC([S-])=S AFCCDDWKHLHPDF-UHFFFAOYSA-M 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 48
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 34
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
- MUBZPKHOEPUJKR-UHFFFAOYSA-M oxalate(1-) Chemical compound OC(=O)C([O-])=O MUBZPKHOEPUJKR-UHFFFAOYSA-M 0.000 description 12
- 239000007858 starting material Substances 0.000 description 12
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 11
- 239000003054 catalyst Substances 0.000 description 10
- DAPZDAPTZFJZTO-UHFFFAOYSA-N heptanoyl heptanoate Chemical compound CCCCCCC(=O)OC(=O)CCCCCC DAPZDAPTZFJZTO-UHFFFAOYSA-N 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 238000002844 melting Methods 0.000 description 9
- 230000008018 melting Effects 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- 235000019341 magnesium sulphate Nutrition 0.000 description 8
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 7
- 235000011114 ammonium hydroxide Nutrition 0.000 description 7
- 238000006264 debenzylation reaction Methods 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- AHTNURPZPBITQJ-UHFFFAOYSA-N [1-(1H-indol-4-yloxy)-4-phenyl-3-(propan-2-ylamino)butan-2-yl] heptanoate Chemical compound C(C1=CC=CC=C1)C(C(COC1=C2C=CNC2=CC=C1)OC(CCCCCC)=O)NC(C)C AHTNURPZPBITQJ-UHFFFAOYSA-N 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 6
- 229910052763 palladium Inorganic materials 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- NOGFHTGYPKWWRX-UHFFFAOYSA-N 2,2,6,6-tetramethyloxan-4-one Chemical compound CC1(C)CC(=O)CC(C)(C)O1 NOGFHTGYPKWWRX-UHFFFAOYSA-N 0.000 description 4
- FWWOWPGPERBCNJ-UHFFFAOYSA-N 2-hydroxy-4-(2-hydroxyethoxy)-4-oxobutanoic acid Chemical compound OCCOC(=O)CC(O)C(O)=O FWWOWPGPERBCNJ-UHFFFAOYSA-N 0.000 description 4
- 239000005711 Benzoic acid Substances 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 150000008064 anhydrides Chemical class 0.000 description 4
- 235000010233 benzoic acid Nutrition 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 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 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 239000000155 melt Substances 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- YKGJUSKLOHNPIM-UHFFFAOYSA-N 1-(1H-indol-4-yloxy)-4-phenyl-3-(propan-2-ylamino)butan-2-ol Chemical compound C(C1=CC=CC=C1)C(C(COC1=C2C=CNC2=CC=C1)O)NC(C)C YKGJUSKLOHNPIM-UHFFFAOYSA-N 0.000 description 2
- IENNOUHEKVPMRP-UHFFFAOYSA-N 2,2-dimethylbutanoyl 2,2-dimethylbutanoate Chemical compound CCC(C)(C)C(=O)OC(=O)C(C)(C)CC IENNOUHEKVPMRP-UHFFFAOYSA-N 0.000 description 2
- SZLQCKQXSGEWSG-UHFFFAOYSA-N 2,2-dimethylpentanoyl 2,2-dimethylpentanoate Chemical compound CCCC(C)(C)C(=O)OC(=O)C(C)(C)CCC SZLQCKQXSGEWSG-UHFFFAOYSA-N 0.000 description 2
- PGZVFRAEAAXREB-UHFFFAOYSA-N 2,2-dimethylpropanoyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC(=O)C(C)(C)C PGZVFRAEAAXREB-UHFFFAOYSA-N 0.000 description 2
- YCURDTPXHPXCKH-UHFFFAOYSA-N 2-ethylbutanoyl 2-ethylbutanoate Chemical compound CCC(CC)C(=O)OC(=O)C(CC)CC YCURDTPXHPXCKH-UHFFFAOYSA-N 0.000 description 2
- BHNHHSOHWZKFOX-UHFFFAOYSA-N 2-methyl-1H-indole Chemical compound C1=CC=C2NC(C)=CC2=C1 BHNHHSOHWZKFOX-UHFFFAOYSA-N 0.000 description 2
- SHQJMIOCGVJBOU-UHFFFAOYSA-N 4-phenylmethoxy-1h-indole-2-carboxamide Chemical class C1=CC=C2NC(C(=O)N)=CC2=C1OCC1=CC=CC=C1 SHQJMIOCGVJBOU-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 238000006683 Mannich reaction Methods 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- JOHUAELJNSBTGS-UHFFFAOYSA-N cyclohexanecarbonyl cyclohexanecarboxylate Chemical compound C1CCCCC1C(=O)OC(=O)C1CCCCC1 JOHUAELJNSBTGS-UHFFFAOYSA-N 0.000 description 2
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 2
- 210000004907 gland Anatomy 0.000 description 2
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
- LSACYLWPPQLVSM-UHFFFAOYSA-N isobutyric acid anhydride Chemical compound CC(C)C(=O)OC(=O)C(C)C LSACYLWPPQLVSM-UHFFFAOYSA-N 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 230000005923 long-lasting effect Effects 0.000 description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- JZQKKSLKJUAGIC-UHFFFAOYSA-N pindolol Chemical compound CC(C)NCC(O)COC1=CC=CC2=C1C=CN2 JZQKKSLKJUAGIC-UHFFFAOYSA-N 0.000 description 2
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 2
- 230000005588 protonation Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
- KKFDJZZADQONDE-UHFFFAOYSA-N (hydridonitrato)hydroxidocarbon(.) Chemical compound O[C]=N KKFDJZZADQONDE-UHFFFAOYSA-N 0.000 description 1
- REHQLKUNRPCYEW-UHFFFAOYSA-N 1-methylcyclohexane-1-carboxylic acid Chemical compound OC(=O)C1(C)CCCCC1 REHQLKUNRPCYEW-UHFFFAOYSA-N 0.000 description 1
- VFHUJFBEFDVZPJ-UHFFFAOYSA-N 1h-indole-2-carboxamide Chemical compound C1=CC=C2NC(C(=O)N)=CC2=C1 VFHUJFBEFDVZPJ-UHFFFAOYSA-N 0.000 description 1
- VUAXHMVRKOTJKP-UHFFFAOYSA-N 2,2-dimethylbutyric acid Chemical compound CCC(C)(C)C(O)=O VUAXHMVRKOTJKP-UHFFFAOYSA-N 0.000 description 1
- PYFVEIDRTLBMHG-UHFFFAOYSA-N 2,3-dimethyl-1h-indole Chemical compound C1=CC=C2C(C)=C(C)NC2=C1 PYFVEIDRTLBMHG-UHFFFAOYSA-N 0.000 description 1
- OXQGTIUCKGYOAA-UHFFFAOYSA-N 2-Ethylbutanoic acid Chemical compound CCC(CC)C(O)=O OXQGTIUCKGYOAA-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- XBVSGEGNQZAQPM-UHFFFAOYSA-N 2-methyl-1h-indol-4-ol Chemical compound C1=CC=C2NC(C)=CC2=C1O XBVSGEGNQZAQPM-UHFFFAOYSA-N 0.000 description 1
- QGWACZFSCSTOCG-UHFFFAOYSA-N 2-methyl-4-phenylmethoxy-1h-indole Chemical compound C1=CC=C2NC(C)=CC2=C1OCC1=CC=CC=C1 QGWACZFSCSTOCG-UHFFFAOYSA-N 0.000 description 1
- CNZSMSLOGCZWBR-UHFFFAOYSA-N 2-propoxy-1h-indole Chemical compound C1=CC=C2NC(OCCC)=CC2=C1 CNZSMSLOGCZWBR-UHFFFAOYSA-N 0.000 description 1
- RYRARARYUZMODI-UHFFFAOYSA-N 3-methyl-1h-indol-4-ol Chemical compound C1=CC(O)=C2C(C)=CNC2=C1 RYRARARYUZMODI-UHFFFAOYSA-N 0.000 description 1
- JFJBEVXWIQBHOX-UHFFFAOYSA-N 3-methyl-4-phenylmethoxy-1H-indole-2-carboxamide Chemical class C(C1=CC=CC=C1)OC1=C2C(=C(NC2=CC=C1)C(=O)N)C JFJBEVXWIQBHOX-UHFFFAOYSA-N 0.000 description 1
- CNKHSQVNZUGHPN-UHFFFAOYSA-N 3-methyl-4-phenylmethoxy-1h-indole-2-carboxylic acid Chemical compound C=12C(C)=C(C(O)=O)NC2=CC=CC=1OCC1=CC=CC=C1 CNKHSQVNZUGHPN-UHFFFAOYSA-N 0.000 description 1
- VEZSZAUUNNYLAQ-UHFFFAOYSA-N 4-[2-hydroxy-3-(propan-2-ylamino)propoxy]-1H-indole-2-carboxamide Chemical compound C(N)(=O)C=1NC2=CC=CC(=C2C1)OCC(CNC(C)C)O VEZSZAUUNNYLAQ-UHFFFAOYSA-N 0.000 description 1
- IPLKGJHGWCVSOG-UHFFFAOYSA-N 4-chlorobutanoic acid Chemical compound OC(=O)CCCCl IPLKGJHGWCVSOG-UHFFFAOYSA-N 0.000 description 1
- CDIIZULDSLKBKV-UHFFFAOYSA-N 4-chlorobutanoyl chloride Chemical compound ClCCCC(Cl)=O CDIIZULDSLKBKV-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- FVKAZTWEBLUVKJ-UHFFFAOYSA-N 4-hydroxy-1h-indole-2-carboxamide Chemical compound C1=CC=C2NC(C(=O)N)=CC2=C1O FVKAZTWEBLUVKJ-UHFFFAOYSA-N 0.000 description 1
- UWDMKTDPDJCJOP-UHFFFAOYSA-N 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-ium-4-carboxylate Chemical compound CC1(C)CC(O)(C(O)=O)CC(C)(C)N1 UWDMKTDPDJCJOP-UHFFFAOYSA-N 0.000 description 1
- NFJBQIZTZRJFEQ-UHFFFAOYSA-N 4-phenylmethoxy-1h-indole-2-carbonyl chloride Chemical compound C1=CC=C2NC(C(=O)Cl)=CC2=C1OCC1=CC=CC=C1 NFJBQIZTZRJFEQ-UHFFFAOYSA-N 0.000 description 1
- GSXFWBDVTDHJFZ-UHFFFAOYSA-N 4-phenylmethoxy-1h-indole-2-carboxylic acid Chemical class C1=CC=C2NC(C(=O)O)=CC2=C1OCC1=CC=CC=C1 GSXFWBDVTDHJFZ-UHFFFAOYSA-N 0.000 description 1
- RREANTFLPGEWEN-MBLPBCRHSA-N 7-[4-[[(3z)-3-[4-amino-5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidin-2-yl]imino-5-fluoro-2-oxoindol-1-yl]methyl]piperazin-1-yl]-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(\N=C/3C4=CC(F)=CC=C4N(CN4CCN(CC4)C=4C(=CC=5C(=O)C(C(O)=O)=CN(C=5C=4)C4CC4)F)C\3=O)=NC=2)N)=C1 RREANTFLPGEWEN-MBLPBCRHSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- SZAQLVMZVXILQQ-UHFFFAOYSA-N C(C1=CC=CC=C1)OC1(N=C2C=CC=CC2=C1C)C(=O)O Chemical class C(C1=CC=CC=C1)OC1(N=C2C=CC=CC2=C1C)C(=O)O SZAQLVMZVXILQQ-UHFFFAOYSA-N 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 230000006181 N-acylation Effects 0.000 description 1
- ANOVRXXKPZVYBI-UHFFFAOYSA-N N1C(=CC2=CC=CC=C12)OC(CC)N Chemical compound N1C(=CC2=CC=CC=C12)OC(CC)N ANOVRXXKPZVYBI-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- PSLVJWSRNOOQOM-UHFFFAOYSA-N [1-(1H-indol-4-yloxy)-3-(propan-2-ylamino)propan-2-yl] acetate Chemical compound C(C)(=O)OC(COC1=C2C=CNC2=CC=C1)CNC(C)C PSLVJWSRNOOQOM-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000003288 anthiarrhythmic effect Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- MEQTXMUTIXTDDL-UHFFFAOYSA-N carbonic acid;cyclohexane Chemical compound OC(O)=O.C1CCCCC1 MEQTXMUTIXTDDL-UHFFFAOYSA-N 0.000 description 1
- 125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 description 1
- RVOJTCZRIKWHDX-UHFFFAOYSA-N cyclohexanecarbonyl chloride Chemical compound ClC(=O)C1CCCCC1 RVOJTCZRIKWHDX-UHFFFAOYSA-N 0.000 description 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000001834 epinephrinelike Effects 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- BJLJBRCPDABXCA-UHFFFAOYSA-N hexyl sulfamate Chemical compound CCCCCCOS(N)(=O)=O BJLJBRCPDABXCA-UHFFFAOYSA-N 0.000 description 1
- 230000001660 hyperkinetic effect Effects 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- LYBKPDDZTNUNNM-UHFFFAOYSA-N isopropylbenzylamine Chemical compound CC(C)NCC1=CC=CC=C1 LYBKPDDZTNUNNM-UHFFFAOYSA-N 0.000 description 1
- 229940039009 isoproterenol Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- AYVIZFVTRRWODF-UHFFFAOYSA-N n,n-dimethyl-1h-indole-2-carboxamide Chemical compound C1=CC=C2NC(C(=O)N(C)C)=CC2=C1 AYVIZFVTRRWODF-UHFFFAOYSA-N 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 229960001749 practolol Drugs 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 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
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- RHHHGLCTQKINES-UHFFFAOYSA-M sodium;5-amino-2-methoxy-4-sulfobenzenesulfonate Chemical compound [Na+].COC1=CC(S(O)(=O)=O)=C(N)C=C1S([O-])(=O)=O RHHHGLCTQKINES-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 125000001424 substituent group Chemical class 0.000 description 1
- 206010042431 subvalvular aortic stenosis Diseases 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- 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
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1446770A CH535763A (de) | 1970-09-30 | 1970-09-30 | Verfahren zur Herstellung neuer Indolderivate |
| CH1489870A CH535764A (de) | 1970-10-08 | 1970-10-08 | Verfahren zur Herstellung neuer Indolderivate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2148553A1 true DE2148553A1 (de) | 1972-04-06 |
Family
ID=25714518
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19712148553 Withdrawn DE2148553A1 (de) | 1970-09-30 | 1971-09-29 | Verfahren zur Herstellung neuer heterocyclischer Verbindungen |
Country Status (9)
| Country | Link |
|---|---|
| JP (1) | JPS5617345B1 (en, 2012) |
| AU (1) | AU469293B2 (en, 2012) |
| BE (1) | BE773206A (en, 2012) |
| DE (1) | DE2148553A1 (en, 2012) |
| ES (1) | ES395496A1 (en, 2012) |
| FR (1) | FR2108098B1 (en, 2012) |
| GB (1) | GB1356310A (en, 2012) |
| NL (1) | NL178592C (en, 2012) |
| SE (1) | SE375771B (en, 2012) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2635209A1 (de) * | 1975-08-15 | 1977-02-24 | Sandoz Ag | Neue 2- methylindolderivate, ihre herstellung und verwendung |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH578526A5 (en, 2012) * | 1972-06-23 | 1976-08-13 | Sandoz Ag |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE675847A (en, 2012) * | 1965-02-01 | 1966-08-01 | ||
| BE734126A (en, 2012) * | 1968-06-07 | 1969-12-05 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2019185A1 (en) * | 1968-09-30 | 1970-06-26 | Sandoz Sa | 4-(2-hydroxy-3-amino-propoxy)-indole-2-carboxy- - lic acids and esters and 2-hydroxymethylindoles as beta |
-
1971
- 1971-09-20 SE SE1189971A patent/SE375771B/xx unknown
- 1971-09-21 NL NL7112936A patent/NL178592C/xx not_active IP Right Cessation
- 1971-09-27 GB GB4481371A patent/GB1356310A/en not_active Expired
- 1971-09-28 AU AU33978/71A patent/AU469293B2/en not_active Expired
- 1971-09-28 ES ES395496A patent/ES395496A1/es not_active Expired
- 1971-09-28 BE BE773206A patent/BE773206A/xx not_active IP Right Cessation
- 1971-09-29 DE DE19712148553 patent/DE2148553A1/de not_active Withdrawn
- 1971-09-29 JP JP7621971A patent/JPS5617345B1/ja active Pending
- 1971-09-29 FR FR7134984A patent/FR2108098B1/fr not_active Expired
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE675847A (en, 2012) * | 1965-02-01 | 1966-08-01 | ||
| BE734126A (en, 2012) * | 1968-06-07 | 1969-12-05 |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2635209A1 (de) * | 1975-08-15 | 1977-02-24 | Sandoz Ag | Neue 2- methylindolderivate, ihre herstellung und verwendung |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5617345B1 (en, 2012) | 1981-04-22 |
| FR2108098B1 (en, 2012) | 1975-06-06 |
| NL7112936A (en, 2012) | 1972-04-05 |
| ES395496A1 (es) | 1974-11-01 |
| FR2108098A1 (en, 2012) | 1972-05-12 |
| AU469293B2 (en) | 1976-02-12 |
| GB1356310A (en) | 1974-06-12 |
| NL178592C (nl) | 1986-04-16 |
| BE773206A (fr) | 1972-03-28 |
| SE375771B (en, 2012) | 1975-04-28 |
| AU3397871A (en) | 1973-04-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0026848B1 (de) | Tetralinderivate, ihre Herstellung und Heilmittel, welche diese Verbindungen enthalten | |
| EP0600949B1 (de) | Neue 3,5-di-tert.butyl-4-hydroxyphenyl-derivate, verfahren zu ihrer herstellung und arzneimittel | |
| DE2938302A1 (de) | Neue derivate des 3-(aminoaethyl)- phenols und deren salze, deren herstellungsverfahren, deren verwendung als arzneimittel und die diese enthaltenden pharmazeutischen zusammensetzungen | |
| DE2113733A1 (de) | Verfahren zur Herstellung neuer heterocyclischer Verbindungen | |
| DE2811031C2 (de) | Piperazino-3-indole, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel | |
| DE2230426A1 (de) | Verfahren zur herstellung neuer heterocyclischer verbindungen | |
| EP0033156A2 (de) | 1-Phenyl-2-cyclohexen-1-alkylamin-Derivate, Verfahren zu deren Herstellung und diese enthaltende Arzneimittel | |
| EP0000395B1 (de) | 2-Piperazinotetraline, ihre Herstellung und Verwendung als Arzneimittel | |
| EP0065295A1 (de) | Substituierte Tryptaminderivate von Thienyloxypropanolaminen, Verfahren zu ihrer Herstellung, pharmazeutische Präparate auf Basis dieser Verbindungen sowie ihre Verwendung | |
| DE2148553A1 (de) | Verfahren zur Herstellung neuer heterocyclischer Verbindungen | |
| DE2748466A1 (de) | 4a-aryloctahydro-1h-2-pyrindine | |
| DE3000625A1 (de) | Cis- und trans-isomere von 3-aryloxy- 4-hydroxypyrrolidinen und deren derivaten, verfahren zu ihrer herstellung und ihre verwendung | |
| DE2331721A1 (de) | Verfahren zur herstellung neuer heterocyclischer verbindungen | |
| EP0029992B1 (de) | Neue Aminopropanolderivate, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel | |
| CH644364A5 (de) | 4-(naphthalinyloxy)piperidin-derivate. | |
| EP0003298A2 (de) | 4-Hydroxy-2-benzimidazolin-thion-Derivate, Verfahren zu deren Herstellung sowie diese Verbindungen enthaltende Arzneimittel | |
| EP0042054B1 (de) | 1-Amino-3-phenyl-indole, deren Salze und diese Indole enthaltende Arzneimittel | |
| CH545783A (en) | Novel indole derivs - prepn by reacting 4-(2-hydroxy-3-isopropylaminopropoxy) indoles and acid anhy-drides | |
| DE2264903A1 (de) | Piperidinderivate | |
| CH643536A5 (de) | Alkanolaminderivate. | |
| DE2237361A1 (de) | (5-indolyloxy)-essigsaeure-derivate und verfahren zur herstellung derselben | |
| DE2031360A1 (de) | Neue cyclische Verbindungen und Ver fahren zu ihrer Herstellung | |
| DD270909A5 (de) | Verfahren zur herstellung von 2,1-benzothiazepin-2,2-dioxid-5-carbonsaeurederivaten | |
| DE1934130A1 (de) | Acylphenylalkylamine und ihre Herstellung | |
| DE2511621A1 (de) | Verfahren zur herstellung neuer heterocyclischer verbindungen |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| OD | Request for examination | ||
| 8139 | Disposal/non-payment of the annual fee |