DD223714A5 - Verfahren zur herstellung von substituierten beta-carbolinderivaten - Google Patents
Verfahren zur herstellung von substituierten beta-carbolinderivaten Download PDFInfo
- Publication number
- DD223714A5 DD223714A5 DD84267607A DD26760784A DD223714A5 DD 223714 A5 DD223714 A5 DD 223714A5 DD 84267607 A DD84267607 A DD 84267607A DD 26760784 A DD26760784 A DD 26760784A DD 223714 A5 DD223714 A5 DD 223714A5
- Authority
- DD
- German Democratic Republic
- Prior art keywords
- carboline
- formula
- carboxylic acid
- methyl
- substituted
- 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 27
- 238000004519 manufacturing process Methods 0.000 title description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 24
- 238000000034 method Methods 0.000 claims abstract description 21
- 238000002360 preparation method Methods 0.000 claims abstract description 13
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 6
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims abstract description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 3
- 150000001336 alkenes Chemical class 0.000 claims abstract description 3
- 150000001350 alkyl halides Chemical class 0.000 claims abstract description 3
- 239000000460 chlorine Substances 0.000 claims abstract description 3
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 3
- 150000004820 halides Chemical class 0.000 claims abstract description 3
- -1 2-amine compound Chemical class 0.000 claims description 48
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 34
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 18
- 229960000583 acetic acid Drugs 0.000 claims description 15
- 239000012362 glacial acetic acid Substances 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 239000012442 inert solvent Substances 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- 238000010992 reflux Methods 0.000 claims description 9
- 239000007868 Raney catalyst Substances 0.000 claims description 8
- 229910000564 Raney nickel Inorganic materials 0.000 claims description 8
- 150000002475 indoles Chemical class 0.000 claims description 8
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 7
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- 238000009835 boiling Methods 0.000 claims description 7
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- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims description 4
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- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 claims description 4
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
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- 125000002015 acyclic group Chemical group 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
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- 125000004185 ester group Chemical group 0.000 claims description 3
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 239000000463 material Substances 0.000 claims description 2
- 229910000510 noble metal Inorganic materials 0.000 claims description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims 1
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- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- 238000002844 melting Methods 0.000 description 28
- 230000008018 melting Effects 0.000 description 28
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 17
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- 239000000203 mixture Substances 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
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- 150000003254 radicals Chemical class 0.000 description 6
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- 239000002904 solvent Substances 0.000 description 5
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- 239000000725 suspension Substances 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
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- 102000004300 GABA-A Receptors Human genes 0.000 description 4
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- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
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- 229910052786 argon Inorganic materials 0.000 description 3
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- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
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- 229960001760 dimethyl sulfoxide Drugs 0.000 description 3
- 229960002200 flunitrazepam Drugs 0.000 description 3
- 229910001385 heavy metal Inorganic materials 0.000 description 3
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- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
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- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
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- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical group 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 125000004849 alkoxymethyl group Chemical group 0.000 description 1
- 150000001348 alkyl chlorides Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 229940054051 antipsychotic indole derivative Drugs 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
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- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
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- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 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 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
- 229960003529 diazepam Drugs 0.000 description 1
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- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000010931 ester hydrolysis Methods 0.000 description 1
- NJSUFZNXBBXAAC-UHFFFAOYSA-N ethanol;toluene Chemical compound CCO.CC1=CC=CC=C1 NJSUFZNXBBXAAC-UHFFFAOYSA-N 0.000 description 1
- RZDDTAKLBSNIQT-UHFFFAOYSA-N ethyl 4-methyl-5-phenyl-9h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C=12C3=C(C)C(C(=O)OCC)=NC=C3NC2=CC=CC=1C1=CC=CC=C1 RZDDTAKLBSNIQT-UHFFFAOYSA-N 0.000 description 1
- DRAGJTJGKWRBHS-UHFFFAOYSA-N ethyl 4-methyl-6-(2-phenylethyl)-9h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1=C2C3=C(C)C(C(=O)OCC)=NC=C3NC2=CC=C1CCC1=CC=CC=C1 DRAGJTJGKWRBHS-UHFFFAOYSA-N 0.000 description 1
- LOFJSNKOCJEDEZ-UHFFFAOYSA-N ethyl 6-(2,3-dimethylbuta-1,3-dienyl)-4-methyl-9h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1=C(C=C(C)C(C)=C)C=C2C3=C(C)C(C(=O)OCC)=NC=C3NC2=C1 LOFJSNKOCJEDEZ-UHFFFAOYSA-N 0.000 description 1
- GWNNKNMMKRGBOM-UHFFFAOYSA-N ethyl 6-(2,3-dimethylbutyl)-4-methyl-9h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1=C(CC(C)C(C)C)C=C2C3=C(C)C(C(=O)OCC)=NC=C3NC2=C1 GWNNKNMMKRGBOM-UHFFFAOYSA-N 0.000 description 1
- LITWQMBLKOVLLX-UHFFFAOYSA-N ethyl 6-(2-cyclohexylethyl)-4-methyl-9h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1=C2C3=C(C)C(C(=O)OCC)=NC=C3NC2=CC=C1CCC1CCCCC1 LITWQMBLKOVLLX-UHFFFAOYSA-N 0.000 description 1
- ASABEFSXQAMSPC-UHFFFAOYSA-N ethyl 6-cycloheptyl-4-methyl-9h-pyrido[3,4-b]indole-3-carboxylate Chemical class C1=C2C3=C(C)C(C(=O)OCC)=NC=C3NC2=CC=C1C1CCCCCC1 ASABEFSXQAMSPC-UHFFFAOYSA-N 0.000 description 1
- VJYXZGFGOFUMLM-UHFFFAOYSA-N ethyl 6-cyclohex-3-en-1-yl-4-methyl-9h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1=C2C3=C(C)C(C(=O)OCC)=NC=C3NC2=CC=C1C1CCC=CC1 VJYXZGFGOFUMLM-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
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- 238000011534 incubation Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- HWUVYUHUUZLYAW-UHFFFAOYSA-N methyl 3-hydroxy-2-nitrobutanoate Chemical compound COC(=O)C(C(C)O)[N+]([O-])=O HWUVYUHUUZLYAW-UHFFFAOYSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- WPHGSKGZRAQSGP-UHFFFAOYSA-N methylenecyclohexane Natural products C1CCCC2CC21 WPHGSKGZRAQSGP-UHFFFAOYSA-N 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- RLZPCFQNZGINRP-UHFFFAOYSA-N n'-hydroxypropanimidamide Chemical compound CCC(N)=NO RLZPCFQNZGINRP-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 150000003018 phosphorus compounds Chemical class 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000000506 psychotropic effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- MWNQXXOSWHCCOZ-UHFFFAOYSA-L sodium;oxido carbonate Chemical compound [Na+].[O-]OC([O-])=O MWNQXXOSWHCCOZ-UHFFFAOYSA-L 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000010414 supernatant solution Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- NBRKLOOSMBRFMH-UHFFFAOYSA-N tert-butyl chloride Chemical compound CC(C)(C)Cl NBRKLOOSMBRFMH-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
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000010626 work up procedure Methods 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Diaphragms For Electromechanical Transducers (AREA)
- Treating Waste Gases (AREA)
- Photoreceptors In Electrophotography (AREA)
- Carbon And Carbon Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE3335323A DE3335323A1 (de) | 1983-09-27 | 1983-09-27 | Substituierte ss-carboline, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DD223714A5 true DD223714A5 (de) | 1985-06-19 |
Family
ID=6210425
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DD84267607A DD223714A5 (de) | 1983-09-27 | 1984-09-25 | Verfahren zur herstellung von substituierten beta-carbolinderivaten |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US4623649A (fr) |
| EP (1) | EP0137390B1 (fr) |
| JP (1) | JPS60100577A (fr) |
| AT (1) | ATE55604T1 (fr) |
| AU (1) | AU578043B2 (fr) |
| CA (1) | CA1263394A (fr) |
| DD (1) | DD223714A5 (fr) |
| DE (2) | DE3335323A1 (fr) |
| DK (1) | DK170256B1 (fr) |
| ES (1) | ES8505368A1 (fr) |
| FI (1) | FI843777L (fr) |
| GR (1) | GR80482B (fr) |
| HU (1) | HU200457B (fr) |
| IE (1) | IE57670B1 (fr) |
| IL (1) | IL73071A (fr) |
| NO (1) | NO160998C (fr) |
| PT (1) | PT79264B (fr) |
| ZA (1) | ZA847619B (fr) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| US5367077A (en) * | 1992-04-08 | 1994-11-22 | Neurogen Corporation | Certain cycloalkyl and azacycloalkyl pyrrolopyridines; a new class of gaba rain receptor ligands |
| AU4117493A (en) * | 1992-04-08 | 1994-11-21 | Neurogen Corporation | Certain aryl fused pyrrolopyrimidines; a new class of gaba brain 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 |
| US5484944A (en) * | 1993-10-27 | 1996-01-16 | Neurogen Corporation | Certain fused pyrrolecarboxanilides and their use as GABA brain receptor ligands |
| US5804686A (en) * | 1996-01-19 | 1998-09-08 | Neurogen Corporation | fused pyrrolecarboxamides; a new class of GABA brain receptor ligands |
| US6211365B1 (en) | 1996-01-19 | 2001-04-03 | Neurogen Corporation | Fused pyrrolecarboxamides; a new class of GABA brain receptor ligands |
| WO1997034870A1 (fr) | 1996-03-22 | 1997-09-25 | Neurogen Corporation | Certains pyrrolecarboxamides fusionnes utilises comme ligands de recepteurs cerebraux gaba |
| 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 |
| US7109351B1 (en) | 1999-08-31 | 2006-09-19 | Neurogen Corporation | Fused pyrrolecarboxamides; GABA brain receptor ligands |
| US20030045541A1 (en) * | 2001-07-23 | 2003-03-06 | Christopher Bruckner | GABA-Receptor modulators with NMDA-Antagonistic activity |
Family Cites Families (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3058909A (en) | 1957-07-23 | 1962-10-16 | Atlantic Refining Co | Method and composition for formation fracturing |
| US3163219A (en) | 1961-06-22 | 1964-12-29 | Atlantic Refining Co | Borate-gum gel breakers |
| US3215634A (en) | 1962-10-16 | 1965-11-02 | Jersey Prod Res Co | Method for stabilizing viscous liquids |
| GB1084257A (fr) * | 1963-11-06 | |||
| US3741894A (en) | 1967-06-15 | 1973-06-26 | Exxon Production Research Co | Chemically modified organic polymers |
| US3696035A (en) | 1970-11-04 | 1972-10-03 | Dow Chemical Co | Well treatments with thickened aqueous alcohol mixtures |
| US3727688A (en) | 1972-02-09 | 1973-04-17 | Phillips Petroleum Co | Hydraulic fracturing method |
| US3768566A (en) | 1972-04-18 | 1973-10-30 | Halliburton Co | Methods for fracturing high temperature well formations |
| US3848673A (en) | 1973-02-26 | 1974-11-19 | Phillips Petroleum Co | Recovery of hydrocarbons |
| US4033415A (en) | 1973-03-30 | 1977-07-05 | Halliburton Company | Methods for fracturing well formations |
| DE2415155C2 (de) | 1974-03-29 | 1985-05-23 | Henkel KGaA, 4000 Düsseldorf | Verfahren zur Herstellung von 2,3-Dihydroxypropylcellulose |
| DE2415154C2 (de) | 1974-03-29 | 1985-05-23 | Henkel KGaA, 4000 Düsseldorf | Verfahren zur Herstellung von Cellulosemischethern, die neben Alkylgruppen, Hydroxyalkylgruppen oder Carboxyalkylgruppen noch 2,3-Dihydroxypropylgruppen enthalten |
| US3888312A (en) | 1974-04-29 | 1975-06-10 | Halliburton Co | Method and compositions for fracturing well formations |
| US3978928A (en) | 1975-04-14 | 1976-09-07 | Phillips Petroleum Company | Process for the production of fluids from subterranean formations |
| US4144179A (en) | 1975-07-21 | 1979-03-13 | Halliburton Company | Composition for treating low temperature subterranean well formations |
| US4096326A (en) | 1976-10-13 | 1978-06-20 | Hercules Incorporated | Dihydroxypropyl cellulose |
| US4323123A (en) | 1978-07-17 | 1982-04-06 | Phillips Petroleum Company | Gelled compositions and well treating |
| DE3023567A1 (de) * | 1980-06-20 | 1982-01-21 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Substituierte (beta) -carbolin-3-carbonsaeurederivate |
| 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 |
| DE3136857A1 (de) * | 1981-09-14 | 1983-03-31 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Substituierte (beta)-carbolin-3-carbonsaeurealkylester, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
| JPS57123180A (en) * | 1980-12-17 | 1982-07-31 | Schering Ag | 3-substituted beta-carboline, manufacture and psychotropic drug containing same |
| DE3048318A1 (de) * | 1980-12-17 | 1982-07-22 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | 4-alkoxyalkyl substituierte (beta)-carbolin-3-carbonsaeurederivate, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
| GB2115408B (en) * | 1982-02-09 | 1985-10-16 | Ici Plc | Triazole and imidazole derivatives |
| DE3240511A1 (de) * | 1982-10-29 | 1984-05-03 | Schering AG, 1000 Berlin und 4709 Bergkamen | Verfahren zur herstellung von ss-carbolinderivaten |
| DE3240513A1 (de) * | 1982-10-29 | 1984-05-03 | Schering AG, 1000 Berlin und 4709 Bergkamen | Indolderivate, verfahren zu ihrer herstellung und deren verwendung zur weiterverarbeitung |
| 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) |
-
1983
- 1983-09-27 DE DE3335323A patent/DE3335323A1/de not_active Withdrawn
-
1984
- 1984-09-22 AT AT84111337T patent/ATE55604T1/de not_active IP Right Cessation
- 1984-09-22 DE DE8484111337T patent/DE3482984D1/de not_active Expired - Lifetime
- 1984-09-22 EP EP84111337A patent/EP0137390B1/fr not_active Expired - Lifetime
- 1984-09-25 PT PT79264A patent/PT79264B/pt not_active IP Right Cessation
- 1984-09-25 DK DK456484A patent/DK170256B1/da not_active IP Right Cessation
- 1984-09-25 DD DD84267607A patent/DD223714A5/de not_active IP Right Cessation
- 1984-09-25 ES ES536199A patent/ES8505368A1/es not_active Expired
- 1984-09-26 IE IE2447/84A patent/IE57670B1/en not_active IP Right Cessation
- 1984-09-26 US US06/654,594 patent/US4623649A/en not_active Expired - Fee Related
- 1984-09-26 NO NO843861A patent/NO160998C/no unknown
- 1984-09-26 AU AU33570/84A patent/AU578043B2/en not_active Ceased
- 1984-09-26 HU HU843650A patent/HU200457B/hu not_active IP Right Cessation
- 1984-09-26 IL IL73071A patent/IL73071A/xx unknown
- 1984-09-26 CA CA000464082A patent/CA1263394A/fr not_active Expired
- 1984-09-26 FI FI843777A patent/FI843777L/fi not_active Application Discontinuation
- 1984-09-26 GR GR80482A patent/GR80482B/el unknown
- 1984-09-27 JP JP59200717A patent/JPS60100577A/ja active Granted
- 1984-09-27 ZA ZA847619A patent/ZA847619B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NO160998B (no) | 1989-03-13 |
| CA1263394A (fr) | 1989-11-28 |
| IL73071A0 (en) | 1984-12-31 |
| FI843777A0 (fi) | 1984-09-26 |
| IL73071A (en) | 1988-06-30 |
| NO160998C (no) | 1989-06-21 |
| GR80482B (en) | 1985-01-28 |
| AU3357084A (en) | 1985-04-04 |
| PT79264A (de) | 1984-10-01 |
| DE3482984D1 (de) | 1990-09-20 |
| DK456484A (da) | 1985-03-28 |
| ZA847619B (en) | 1985-05-29 |
| US4623649A (en) | 1986-11-18 |
| ES536199A0 (es) | 1985-06-01 |
| JPH0586390B2 (fr) | 1993-12-10 |
| PT79264B (de) | 1986-08-08 |
| HU200457B (en) | 1990-06-28 |
| IE57670B1 (en) | 1993-02-24 |
| EP0137390A1 (fr) | 1985-04-17 |
| AU578043B2 (en) | 1988-10-13 |
| DE3335323A1 (de) | 1985-04-04 |
| FI843777L (fi) | 1985-03-28 |
| IE842447L (en) | 1985-03-27 |
| ES8505368A1 (es) | 1985-06-01 |
| EP0137390B1 (fr) | 1990-08-16 |
| JPS60100577A (ja) | 1985-06-04 |
| DK456484D0 (da) | 1984-09-25 |
| NO843861L (no) | 1985-03-28 |
| HUT35673A (en) | 1985-07-29 |
| DK170256B1 (da) | 1995-07-17 |
| ATE55604T1 (de) | 1990-09-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| VZ | Disclaimer of patent (art. 11 and 12 extension act) |