IE53931B1 - 3-substituted beta-carbolines, process for their production and compositions containing them - Google Patents
3-substituted beta-carbolines, process for their production and compositions containing themInfo
- Publication number
- IE53931B1 IE53931B1 IE2954/81A IE295481A IE53931B1 IE 53931 B1 IE53931 B1 IE 53931B1 IE 2954/81 A IE2954/81 A IE 2954/81A IE 295481 A IE295481 A IE 295481A IE 53931 B1 IE53931 B1 IE 53931B1
- Authority
- IE
- Ireland
- Prior art keywords
- atoms
- hydrogen
- beta
- carboline
- formula
- Prior art date
Links
- AIFRHYZBTHREPW-UHFFFAOYSA-N β-carboline Chemical class N1=CC=C2C3=CC=CC=C3NC2=C1 AIFRHYZBTHREPW-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 239000000203 mixture Substances 0.000 title claims description 42
- 238000000034 method Methods 0.000 title claims description 25
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 78
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 77
- 150000001875 compounds Chemical class 0.000 claims abstract description 74
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 56
- 239000001257 hydrogen Substances 0.000 claims abstract description 51
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 30
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 17
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 14
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 14
- 125000003118 aryl group Chemical group 0.000 claims abstract description 12
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 10
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 9
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 9
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 8
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 8
- 150000002367 halogens Chemical class 0.000 claims abstract description 8
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 8
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims abstract description 7
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims abstract description 7
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 7
- 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 claims abstract description 5
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 5
- 239000003204 tranquilizing agent Substances 0.000 claims abstract description 5
- 230000002936 tranquilizing effect Effects 0.000 claims abstract description 5
- JCXJVPUVTGWSNB-UHFFFAOYSA-N nitrogen dioxide Inorganic materials O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims abstract description 3
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 3
- 150000002431 hydrogen Chemical class 0.000 claims abstract 12
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 64
- -1 amino compound Chemical class 0.000 claims description 30
- 239000002253 acid Substances 0.000 claims description 13
- 230000015572 biosynthetic process Effects 0.000 claims description 13
- 239000000460 chlorine Substances 0.000 claims description 13
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 12
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 11
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 10
- ARLVFKCLBYUINL-UHFFFAOYSA-N 9h-pyrido[3,4-b]indole-3-carboxylic acid Chemical class N1C2=CC=CC=C2C2=C1C=NC(C(=O)O)=C2 ARLVFKCLBYUINL-UHFFFAOYSA-N 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 5
- 150000002828 nitro derivatives Chemical class 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 4
- SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 claims description 4
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- 150000002475 indoles Chemical class 0.000 claims description 4
- 238000007363 ring formation reaction Methods 0.000 claims description 4
- RYLDZJANGRBUGW-UHFFFAOYSA-N 9h-pyrido[3,4-b]indole-3-carbonitrile Chemical compound N1C2=CC=CC=C2C2=C1C=NC(C#N)=C2 RYLDZJANGRBUGW-UHFFFAOYSA-N 0.000 claims description 3
- 125000005907 alkyl ester group Chemical group 0.000 claims description 3
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 3
- 125000002534 ethynyl group Chemical class [H]C#C* 0.000 claims description 3
- 150000004820 halides Chemical class 0.000 claims description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 3
- 239000011707 mineral Substances 0.000 claims description 3
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 230000002140 halogenating effect Effects 0.000 claims description 2
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 claims description 2
- 230000000802 nitrating effect Effects 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 101100240530 Caenorhabditis elegans nhr-27 gene Proteins 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- WFPXOWCKXUEKCA-UHFFFAOYSA-N ethyl 4-(methoxymethyl)-5-phenylmethoxy-9h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C=12C3=C(COC)C(C(=O)OCC)=NC=C3NC2=CC=CC=1OCC1=CC=CC=C1 WFPXOWCKXUEKCA-UHFFFAOYSA-N 0.000 claims 1
- 229940125725 tranquilizer Drugs 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 12
- 229910052760 oxygen Inorganic materials 0.000 abstract description 4
- 230000000506 psychotropic effect Effects 0.000 abstract description 2
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 3
- 125000000041 C6-C10 aryl group Chemical group 0.000 abstract 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract 2
- 239000001301 oxygen Substances 0.000 abstract 2
- 125000004430 oxygen atom Chemical group O* 0.000 abstract 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 abstract 1
- 125000002648 azanetriyl group Chemical group *N(*)* 0.000 abstract 1
- 125000005843 halogen group Chemical group 0.000 abstract 1
- 125000004043 oxo group Chemical group O=* 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 115
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 100
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 54
- 239000000243 solution Substances 0.000 description 44
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
- 229940093499 ethyl acetate Drugs 0.000 description 33
- 235000019439 ethyl acetate Nutrition 0.000 description 33
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 29
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 22
- 229940073584 methylene chloride Drugs 0.000 description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
- 239000000741 silica gel Substances 0.000 description 20
- 229910002027 silica gel Inorganic materials 0.000 description 20
- 229960001866 silicon dioxide Drugs 0.000 description 20
- 239000002904 solvent Substances 0.000 description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- 239000003921 oil Substances 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- 238000001816 cooling Methods 0.000 description 14
- 239000000126 substance Substances 0.000 description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
- 229960000583 acetic acid Drugs 0.000 description 13
- 239000002994 raw material Substances 0.000 description 13
- 238000010992 reflux Methods 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 238000001704 evaporation Methods 0.000 description 11
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 10
- 238000002425 crystallisation Methods 0.000 description 10
- 239000012362 glacial acetic acid Substances 0.000 description 10
- 229910052757 nitrogen Inorganic materials 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- 230000008025 crystallization Effects 0.000 description 9
- 238000000354 decomposition reaction Methods 0.000 description 9
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- 239000002244 precipitate Substances 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- 238000005755 formation reaction Methods 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 6
- 229960002200 flunitrazepam Drugs 0.000 description 6
- 239000005457 ice water Substances 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 229910052763 palladium Inorganic materials 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 5
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-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
- 239000002585 base Substances 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
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- IUHKSTINHDUYRO-UHFFFAOYSA-N ethyl 4-(methoxymethyl)-9h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1=CC=C2C3=C(COC)C(C(=O)OCC)=NC=C3NC2=C1 IUHKSTINHDUYRO-UHFFFAOYSA-N 0.000 description 5
- 239000012442 inert solvent Substances 0.000 description 5
- 239000011630 iodine Substances 0.000 description 5
- 235000011121 sodium hydroxide Nutrition 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 4
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 4
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- 102000004300 GABA-A Receptors Human genes 0.000 description 4
- 108090000839 GABA-A Receptors Proteins 0.000 description 4
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- 238000006073 displacement reaction Methods 0.000 description 4
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- 125000001424 substituent group Chemical group 0.000 description 3
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- ULTHEAFYOOPTTB-UHFFFAOYSA-N 1,4-dibromobutane Chemical compound BrCCCCBr ULTHEAFYOOPTTB-UHFFFAOYSA-N 0.000 description 2
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- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 2
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- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- YONPGGFAJWQGJC-UHFFFAOYSA-K titanium(iii) chloride Chemical compound Cl[Ti](Cl)Cl YONPGGFAJWQGJC-UHFFFAOYSA-K 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 150000003654 tryptophanes Chemical class 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- 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
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/20—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals substituted additionally by nitrogen atoms, e.g. tryptophane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurosurgery (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Anesthesiology (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19803048318 DE3048318A1 (de) | 1980-12-17 | 1980-12-17 | 4-alkoxyalkyl substituierte (beta)-carbolin-3-carbonsaeurederivate, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
| DK91381 | 1981-02-27 | ||
| DE19813136857 DE3136857A1 (de) | 1981-09-14 | 1981-09-14 | Substituierte (beta)-carbolin-3-carbonsaeurealkylester, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE812954L IE812954L (en) | 1982-06-17 |
| IE53931B1 true IE53931B1 (en) | 1989-04-26 |
Family
ID=27189019
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE2954/81A IE53931B1 (en) | 1980-12-17 | 1981-12-16 | 3-substituted beta-carbolines, process for their production and compositions containing them |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US4435403A (enExample) |
| EP (1) | EP0054507B1 (enExample) |
| JP (1) | JPS57123180A (enExample) |
| AT (1) | ATE32513T1 (enExample) |
| AU (1) | AU558450B2 (enExample) |
| CA (1) | CA1188300A (enExample) |
| DD (1) | DD161210A5 (enExample) |
| DE (1) | DE3176650D1 (enExample) |
| EG (1) | EG17159A (enExample) |
| ES (1) | ES508073A0 (enExample) |
| HU (1) | HU187395B (enExample) |
| IE (1) | IE53931B1 (enExample) |
| IL (1) | IL64560A (enExample) |
| NZ (1) | NZ199312A (enExample) |
| PT (1) | PT74143B (enExample) |
| RO (1) | RO82164A (enExample) |
Families Citing this family (54)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ194747A (en) * | 1979-08-29 | 1988-11-29 | Schering Ag | 9h-pyrido(3,4-b)indol-3-ylcarboxylic acid derivatives |
| DE3240514A1 (de) * | 1982-10-29 | 1984-05-03 | Schering AG, 1000 Berlin und 4709 Bergkamen | Ss-carboline, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische praeparate |
| DK151808C (da) * | 1982-11-16 | 1988-06-20 | Ferrosan As | Analogifremgangsmaade til fremstilling af oxadiazolylimidazo-oe1,4aa-benzodiazepinderivater |
| DE3246932A1 (de) * | 1982-12-16 | 1984-06-20 | Schering AG, 1000 Berlin und 4709 Bergkamen | Substituierte 5h-pyrimido(5,4-b)indole |
| DK149270C (da) * | 1983-05-27 | 1986-08-25 | Schering Ag | Analogifremgangsmaade til fremstilling af beta-carbolin-3-carboxylsyrederivater |
| DE3322894A1 (de) * | 1983-06-23 | 1985-01-03 | Schering AG, 1000 Berlin und 4709 Bergkamen | Neue (beta)-carboline, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel (h) |
| DE3322895A1 (de) * | 1983-06-23 | 1985-01-03 | Schering AG, 1000 Berlin und 4709 Bergkamen | Neue ss-carboline, verfahren zur ihrer herstellung und ihre verwendung als arzneimittel (s) |
| US4631149A (en) * | 1983-07-25 | 1986-12-23 | University Of Illinois | Antiviral eudistomins from a marine tunicate |
| DE3335323A1 (de) | 1983-09-27 | 1985-04-04 | Schering AG, 1000 Berlin und 4709 Bergkamen | Substituierte ss-carboline, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
| NZ210850A (en) * | 1984-01-19 | 1988-10-28 | Hoffmann La Roche | Imidazodiazepine derivatives and pharmaceutical compositions |
| DK240084D0 (da) * | 1984-05-15 | 1984-05-15 | Ferrosan As | New beta-carboline-3-oxadiazolyl derivatives |
| DK240184D0 (da) * | 1984-05-15 | 1984-05-15 | Ferrosan As | Beta-carboline-3-carboxylic acid derivatives and method of preparing the same |
| GB8432073D0 (en) * | 1984-12-19 | 1985-01-30 | Roussel Lab Ltd | Chemical compounds |
| DE3504045A1 (de) * | 1985-02-04 | 1986-08-07 | Schering AG, 1000 Berlin und 4709 Bergkamen | Verfahren zur herstellung von ss-carbolinen durch dehydrierung |
| AU587802B2 (en) * | 1985-03-08 | 1989-08-31 | Ferrosan A/S | Novel oxadiazolyl imidazobenzodiazepine derivatives and methods of preparing such compounds |
| US4745112A (en) * | 1985-05-17 | 1988-05-17 | A/S Ferrosan | Oxadiazolylimidazobenzodiazepine, compositions, and method III |
| US4622320A (en) * | 1985-05-17 | 1986-11-11 | As Ferrosan | Oxadiazolylimidazobenzodiazepine, compositions, and method |
| DE3535927A1 (de) * | 1985-10-04 | 1987-04-09 | Schering Ag | 3-vinyl- und 3-ethinyl-ss-carbolinderivate, ihre herstellung und ihre verwendung als arzneimittel |
| DE3540653A1 (de) * | 1985-11-13 | 1987-05-14 | Schering Ag | Neue 3-oxadiazol- und 3-carbonsaeure-ss-carbolinderivate, ihre herstellung und ihre verwendung als arzneimittel |
| DE3540654A1 (de) | 1985-11-13 | 1987-05-14 | Schering Ag | Phenoxy-substituierte ss-carbolinderivate, ihre herstellung und ihre verwendung als arzneimittel |
| DE3545776A1 (de) * | 1985-12-20 | 1987-06-25 | Schering Ag | 5-aminoalkyl-ss-carbolinderivate, ihre herstellung und ihre verwendung als arzneimittel |
| US4952584A (en) * | 1986-01-11 | 1990-08-28 | Beecham Group P.L.C. | 9H-pyrido[2,B-8]indole-3-carboxylic acid ester compounds having useful pharmaceutical activity |
| DE3609699A1 (de) * | 1986-03-20 | 1987-09-24 | Schering Ag | 5- oder 6-substituierte-(beta)-carbolin-3-carbonsaeureester |
| DE3608089A1 (de) * | 1986-03-08 | 1987-09-10 | Schering Ag | Heteroaryl-oxy-ss-carbolinderivate, ihre herstellung und ihre verwendung als arzneimittel |
| DK174086D0 (da) * | 1986-04-16 | 1986-04-16 | Ferrosan As | Nye benzodiazepinderivater samt fremgangsmaade til fremstilling af samme |
| EP0304223A3 (en) * | 1987-08-17 | 1990-10-24 | Merck & Co. Inc. | Beta-carbolines as cholecy-stokinin and gastrin antagonist |
| AU619203B2 (en) * | 1987-08-28 | 1992-01-23 | Schering Aktiengesellschaft | Isoxazole-beta-carboline derivatives |
| DE3729370C2 (de) * | 1987-08-31 | 1995-04-20 | Schering Ag | Verfahren zur Herstellung von 4-Alkoxyalkyl-beta-carbolinen |
| DE3943225A1 (de) * | 1989-12-23 | 1991-06-27 | Schering Ag | Neue ss-carboline, verfahren zu deren herstellung und deren verwendung in arzneimitteln |
| DE4013907A1 (de) * | 1990-04-26 | 1991-10-31 | Schering Ag | Verfahren zur herstellung von gramin-derivaten |
| DE4029389A1 (de) * | 1990-09-13 | 1992-03-26 | Schering Ag | Verfahren zur herstellung von (beta)-carbolin-derivaten |
| US5350750A (en) * | 1991-04-27 | 1994-09-27 | Schering Aktiengesellschaft | β-carboline-3-hydroxyalkylcarboxylic acid ester derivatives, process for their production and their use in pharmaceutical agents |
| US5543519A (en) * | 1991-06-15 | 1996-08-06 | Schering Aktiengesellschaft | 3-aryl or 3-hetaryl-β-carbolines, their production and use in pharmaceutical agents |
| DE4120109A1 (de) * | 1991-06-15 | 1992-12-17 | Schering Ag | 3-aryl- oder 3-hetaryl-(beta)-carboline, deren herstellung und verwendung in arzneimitteln |
| DE4122722A1 (de) * | 1991-07-06 | 1993-01-07 | Schering Ag | Verfahren zur herstellung von indol-derivaten |
| DE4130933A1 (de) * | 1991-09-13 | 1993-03-18 | Schering Ag | Neue (beta)-carbolinderivate, deren herstellung und verwendung in arzneimitteln |
| US5585490A (en) * | 1991-10-08 | 1996-12-17 | Neurogen Corporation | Certain cycloalkyl and azacycloalkyl pyrrolopyrimidines; a new class of GABA brain receptor ligands |
| WO1994025463A1 (en) * | 1992-04-08 | 1994-11-10 | Neurogen Corporation | Certain aryl fused pyrrolopyrimidines; a new class of gaba brain receptor ligands |
| US5367077A (en) * | 1992-04-08 | 1994-11-22 | Neurogen Corporation | Certain cycloalkyl and azacycloalkyl pyrrolopyridines; a new class of gaba rain receptor ligands |
| US5286860A (en) * | 1992-11-12 | 1994-02-15 | Neurogen Corporation | Certain aryl substituted pyrrolopyrazines; a new class of GABA brain receptor ligands |
| US5750702A (en) * | 1993-10-27 | 1998-05-12 | Neurogen Corporation | Certain pyrrolo pyridine-3-carboxamides; a new class of GABA brain receptor ligands |
| DE4330175A1 (de) * | 1993-08-31 | 1995-03-02 | Schering Ag | Alkoxy-substituierte beta-Carboline |
| US5484944A (en) * | 1993-10-27 | 1996-01-16 | Neurogen Corporation | Certain fused pyrrolecarboxanilides and their use as GABA brain receptor ligands |
| US6211365B1 (en) | 1996-01-19 | 2001-04-03 | Neurogen Corporation | Fused pyrrolecarboxamides; a new class of GABA brain receptor ligands |
| US5804686A (en) * | 1996-01-19 | 1998-09-08 | Neurogen Corporation | fused pyrrolecarboxamides; a new class of GABA brain receptor ligands |
| EP0888300A1 (en) | 1996-03-22 | 1999-01-07 | Neurogen Corporation | Certain fused pyrrolecarboxamides as gaba brain receptor ligands |
| US5723462A (en) * | 1996-04-26 | 1998-03-03 | Neurogen Corporation | Certain fused pyrrolecarboxamides a new class of GABA brain receptor ligands |
| US20050014939A1 (en) * | 1999-08-31 | 2005-01-20 | Neurogen Corporation | Fused pyrrolecarboxamides: GABA brain receptor ligands |
| EE200200111A (et) * | 1999-08-31 | 2003-06-16 | Neurogen Corporation | Kondenseerunud pürroolkarboksamiidid: aju GABA-retseptori ligandid |
| US20040253891A1 (en) * | 2000-09-12 | 2004-12-16 | Schierenbeck Alan W. | Composite structure for protective garment |
| US20050143371A1 (en) * | 2003-07-23 | 2005-06-30 | Pharmacia Corporation | Beta-carboline compounds and analogues thereof as mitogen-activated protein kinase-activated protein kinase-2 inhibitors |
| FR2953837B1 (fr) * | 2009-12-10 | 2012-03-09 | Sanofi Aventis | Derives 9h-pyridino[3,4-b]indole disubstitues, leur preparation et leur utilisation therapeutique |
| FR2953838B1 (fr) * | 2009-12-10 | 2012-02-24 | Sanofi Aventis | Derives de 9h-beta-carboline (ou 9h-pyridino[3,4-b]indole) trisubstitues, leur preparation et leur utilisation therapeutique |
| EP3860996A4 (en) | 2018-10-02 | 2022-08-31 | Northwestern University | BETA-CARBOLINES AS POSITIVE ALLOSTERIC MODULATORS OF HUMAN SEROTONIN RECEPTOR 2C (5-HT2C) |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA786351A (en) | 1968-05-28 | Leonard Frederick | PROCESS FOR THE PREPARATION OF NEW .beta.-CARBOLIN-CARBOXYLIC ACID AMIDE DERIVATIVES | |
| FR894620A (fr) | 1943-02-08 | 1944-12-29 | Barrere & Cie M | Embrayeur-inverseur pour la commande des arbres porte-hélice des bateaux |
| ES273769A1 (es) * | 1961-01-18 | 1962-06-01 | Geigy Ag J R | Procedimiento para la preparaciën de nuevos derivados de amidas de acido beta-carbolin-carboxilico |
| FR2306693A1 (fr) * | 1975-04-11 | 1976-11-05 | Roussel Uclaf | Nouveaux derives du /9h/pyrido/3,4-b/ indole et leurs sels, procede de preparation et application a titre de medicaments |
| FR2455044A1 (fr) * | 1979-04-26 | 1980-11-21 | Synthelabo | Pyrido-indoles et leur application en therapeutique |
| NZ194747A (en) * | 1979-08-29 | 1988-11-29 | Schering Ag | 9h-pyrido(3,4-b)indol-3-ylcarboxylic acid derivatives |
| JPS574987A (en) * | 1980-06-09 | 1982-01-11 | Sankyo Co Ltd | Pyridoindolecarboxylic acid derivative and its preparation |
-
1981
- 1981-12-14 JP JP56200237A patent/JPS57123180A/ja active Granted
- 1981-12-15 EP EP81730122A patent/EP0054507B1/en not_active Expired
- 1981-12-15 DE DE8181730122T patent/DE3176650D1/de not_active Expired
- 1981-12-15 IL IL64560A patent/IL64560A/xx not_active IP Right Cessation
- 1981-12-15 RO RO81106006A patent/RO82164A/ro unknown
- 1981-12-15 AT AT81730122T patent/ATE32513T1/de not_active IP Right Cessation
- 1981-12-16 HU HU813799A patent/HU187395B/hu not_active IP Right Cessation
- 1981-12-16 CA CA000392470A patent/CA1188300A/en not_active Expired
- 1981-12-16 DD DD81235831A patent/DD161210A5/de not_active IP Right Cessation
- 1981-12-16 EG EG741/81A patent/EG17159A/xx active
- 1981-12-16 PT PT74143A patent/PT74143B/pt not_active IP Right Cessation
- 1981-12-16 IE IE2954/81A patent/IE53931B1/en not_active IP Right Cessation
- 1981-12-17 NZ NZ199312A patent/NZ199312A/xx unknown
- 1981-12-17 US US06/331,740 patent/US4435403A/en not_active Expired - Lifetime
- 1981-12-17 AU AU78592/81A patent/AU558450B2/en not_active Ceased
- 1981-12-17 ES ES508073A patent/ES508073A0/es active Granted
-
1983
- 1983-12-01 US US06/556,869 patent/US4596808A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP0054507A3 (en) | 1982-09-15 |
| RO82164B (ro) | 1983-06-30 |
| CA1188300A (en) | 1985-06-04 |
| EG17159A (en) | 1990-12-30 |
| PT74143A (de) | 1982-01-01 |
| NZ199312A (en) | 1989-08-29 |
| ATE32513T1 (de) | 1988-03-15 |
| US4596808A (en) | 1986-06-24 |
| JPH0557274B2 (enExample) | 1993-08-23 |
| ES8301984A1 (es) | 1983-02-01 |
| AU7859281A (en) | 1982-06-24 |
| RO82164A (ro) | 1983-07-07 |
| ES508073A0 (es) | 1983-02-01 |
| IE812954L (en) | 1982-06-17 |
| AU558450B2 (en) | 1987-01-29 |
| IL64560A (en) | 1988-05-31 |
| EP0054507B1 (en) | 1988-02-17 |
| DE3176650D1 (en) | 1988-03-24 |
| HU187395B (en) | 1985-12-28 |
| PT74143B (de) | 1983-05-16 |
| JPS57123180A (en) | 1982-07-31 |
| IL64560A0 (en) | 1982-03-31 |
| EP0054507A2 (en) | 1982-06-23 |
| DD161210A5 (de) | 1985-06-12 |
| US4435403A (en) | 1984-03-06 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Patent lapsed |