DD152935A5 - Substituierte beta-carbolin-3-carbonsaeure-derivate - Google Patents

Substituierte beta-carbolin-3-carbonsaeure-derivate Download PDF

Info

Publication number: DD152935A5
Authority: DD; German Democratic Republic
Prior art keywords: carboline; carboxylic acid; compound; general formula; group
Prior art date: 1979-08-29

Application number

DD80223673A

Other languages

German (de)

English (en)

Inventor

Ulrich Eder

Guenter Neef

Andreas Huth

Dieter Rahtz

Ralph Schmiechen

Claus T Braestrup

Mogens C Nielsen

Joergen A Christensen

Mogens Engelstoft

Henning Schou

Original Assignee

Schering Ag

Priority date (The priority date 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 date listed.)

1979-08-29

Filing date

1980-08-29

Publication date

1981-12-16

1980-02-29 Priority claimed from DK88980A external-priority patent/DK88980A/da

1980-04-22 Priority claimed from DE19803015816 external-priority patent/DE3015816A1/de

1980-06-20 Priority claimed from DE19803023567 external-priority patent/DE3023567A1/de

1980-08-29 Application filed by Schering Ag filed Critical Schering Ag

1981-12-16 Publication of DD152935A5 publication Critical patent/DD152935A5/de

Links

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 title claims abstract description 23
238000000034 method Methods 0.000 claims abstract description 50
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 25
125000000217 alkyl group Chemical group 0.000 claims abstract description 23
230000008569 process Effects 0.000 claims abstract description 20
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 13
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 12
238000002360 preparation method Methods 0.000 claims abstract description 12
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 11
125000003545 alkoxy group Chemical group 0.000 claims abstract description 10
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 9
229910052794 bromium Inorganic materials 0.000 claims abstract description 9
229910052717 sulfur Inorganic materials 0.000 claims abstract description 8
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 7
125000003118 aryl group Chemical group 0.000 claims abstract description 6
125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 5
125000004104 aryloxy group Chemical group 0.000 claims abstract description 4
229910052760 oxygen Inorganic materials 0.000 claims abstract description 3
239000001301 oxygen Substances 0.000 claims abstract description 3
150000001875 compounds Chemical class 0.000 claims description 99
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 67
-1 imino compound Chemical class 0.000 claims description 57
101000588924 Anthopleura elegantissima Delta-actitoxin-Ael1a Proteins 0.000 claims description 42
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 28
238000006243 chemical reaction Methods 0.000 claims description 18
150000002148 esters Chemical class 0.000 claims description 14
239000002253 acid Substances 0.000 claims description 12
238000006467 substitution reaction Methods 0.000 claims description 11
238000005886 esterification reaction Methods 0.000 claims description 8
229910052757 nitrogen Inorganic materials 0.000 claims description 8
125000004430 oxygen atom Chemical group O* 0.000 claims description 8
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 8
150000001408 amides Chemical class 0.000 claims description 7
230000032050 esterification Effects 0.000 claims description 6
125000004429 atom Chemical group 0.000 claims description 5
239000000460 chlorine Substances 0.000 claims description 5
229910052801 chlorine Inorganic materials 0.000 claims description 5
125000001424 substituent group Chemical group 0.000 claims description 5
125000003277 amino group Chemical group 0.000 claims description 4
125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
230000015572 biosynthetic process Effects 0.000 claims description 3
230000009467 reduction Effects 0.000 claims description 3
125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 2
125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 2
125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 2
125000005036 alkoxyphenyl group Chemical group 0.000 claims description 2
238000006356 dehydrogenation reaction Methods 0.000 claims description 2
AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 claims description 2
230000002140 halogenating effect Effects 0.000 claims description 2
125000000623 heterocyclic group Chemical group 0.000 claims description 2
150000002772 monosaccharides Chemical class 0.000 claims description 2
238000006396 nitration reaction Methods 0.000 claims description 2
229910052698 phosphorus Inorganic materials 0.000 claims description 2
125000004434 sulfur atom Chemical group 0.000 claims description 2
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims 1
241000088844 Nothocestrum Species 0.000 claims 1
125000005518 carboxamido group Chemical group 0.000 claims 1
238000012216 screening Methods 0.000 claims 1
229910052739 hydrogen Inorganic materials 0.000 abstract description 10
239000001257 hydrogen Substances 0.000 abstract description 9
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract description 7
230000000694 effects Effects 0.000 abstract description 7
239000011593 sulfur Chemical group 0.000 abstract description 6
230000033001 locomotion Effects 0.000 abstract description 5
210000003169 central nervous system Anatomy 0.000 abstract description 4
230000009471 action Effects 0.000 abstract description 2
229910052731 fluorine Inorganic materials 0.000 abstract description 2
101100439746 Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4) cinA gene Proteins 0.000 abstract 2
101100275845 Streptococcus pneumoniae (strain ATCC BAA-255 / R6) cshA gene Proteins 0.000 abstract 1
101100439974 Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4) clpE gene Proteins 0.000 abstract 1
101100072620 Streptomyces griseus ind2 gene Proteins 0.000 abstract 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract 1
101150109310 msrAB1 gene Proteins 0.000 abstract 1
238000002844 melting Methods 0.000 description 83
230000008018 melting Effects 0.000 description 83
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 60
239000000203 mixture Substances 0.000 description 59
239000000243 solution Substances 0.000 description 43
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 34
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 27
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 26
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
238000000354 decomposition reaction Methods 0.000 description 25
238000001816 cooling Methods 0.000 description 23
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 19
239000002904 solvent Substances 0.000 description 19
239000000126 substance Substances 0.000 description 19
AIFRHYZBTHREPW-UHFFFAOYSA-N β-carboline Chemical compound N1=CC=C2C3=CC=CC=C3NC2=C1 AIFRHYZBTHREPW-UHFFFAOYSA-N 0.000 description 19
KOVRZNUMIKACTB-UHFFFAOYSA-N 9H-pyrido[3,4-b]indole-3-carboxylic acid ethyl ester Chemical compound N1C2=CC=CC=C2C2=C1C=NC(C(=O)OCC)=C2 KOVRZNUMIKACTB-UHFFFAOYSA-N 0.000 description 18
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
238000009835 boiling Methods 0.000 description 16
238000001704 evaporation Methods 0.000 description 16
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
230000008020 evaporation Effects 0.000 description 15
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 15
239000011541 reaction mixture Substances 0.000 description 15
239000000725 suspension Substances 0.000 description 15
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 13
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
239000008096 xylene Substances 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 12
239000000741 silica gel Substances 0.000 description 12
229910002027 silica gel Inorganic materials 0.000 description 12
241000700159 Rattus Species 0.000 description 11
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 11
150000001732 carboxylic acid derivatives Chemical class 0.000 description 11
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
238000000605 extraction Methods 0.000 description 10
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
102100040141 Aminopeptidase O Human genes 0.000 description 9
108050008333 Aminopeptidase O Proteins 0.000 description 9
241000699670 Mus sp. Species 0.000 description 9
150000001412 amines Chemical class 0.000 description 9
229910021529 ammonia Inorganic materials 0.000 description 9
239000003054 catalyst Substances 0.000 description 9
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
238000001914 filtration Methods 0.000 description 9
239000005457 ice water Substances 0.000 description 9
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
239000007787 solid Substances 0.000 description 9
239000007858 starting material Substances 0.000 description 9
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 8
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
235000011114 ammonium hydroxide Nutrition 0.000 description 8
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
229910000041 hydrogen chloride Inorganic materials 0.000 description 8
MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 description 8
239000002244 precipitate Substances 0.000 description 8
238000010992 reflux Methods 0.000 description 8
238000003756 stirring Methods 0.000 description 8
238000012360 testing method Methods 0.000 description 8
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 7
238000001035 drying Methods 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
239000000047 product Substances 0.000 description 7
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
229910052938 sodium sulfate Inorganic materials 0.000 description 7
235000011152 sodium sulphate Nutrition 0.000 description 7
238000004809 thin layer chromatography Methods 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 6
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
125000004494 ethyl ester group Chemical group 0.000 description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
229940049706 benzodiazepine Drugs 0.000 description 5
UXTMROKLAAOEQO-UHFFFAOYSA-N chloroform;ethanol Chemical compound CCO.ClC(Cl)Cl UXTMROKLAAOEQO-UHFFFAOYSA-N 0.000 description 5
238000004587 chromatography analysis Methods 0.000 description 5
239000012043 crude product Substances 0.000 description 5
229960002200 flunitrazepam Drugs 0.000 description 5
230000005764 inhibitory process Effects 0.000 description 5
229910017604 nitric acid Inorganic materials 0.000 description 5
229920006395 saturated elastomer Polymers 0.000 description 5
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
PPTYJKAXVCCBDU-UHFFFAOYSA-N Rohypnol Chemical compound N=1CC(=O)N(C)C2=CC=C([N+]([O-])=O)C=C2C=1C1=CC=CC=C1F PPTYJKAXVCCBDU-UHFFFAOYSA-N 0.000 description 4
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
230000016571 aggressive behavior Effects 0.000 description 4
239000008346 aqueous phase Substances 0.000 description 4
150000001557 benzodiazepines Chemical class 0.000 description 4
ANTSCNMPPGJYLG-UHFFFAOYSA-N chlordiazepoxide Chemical compound O=N=1CC(NC)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 ANTSCNMPPGJYLG-UHFFFAOYSA-N 0.000 description 4
QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 4
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 4
229960003529 diazepam Drugs 0.000 description 4
238000006073 displacement reaction Methods 0.000 description 4
238000002474 experimental method Methods 0.000 description 4
239000000284 extract Substances 0.000 description 4
239000007789 gas Substances 0.000 description 4
238000010438 heat treatment Methods 0.000 description 4
239000008101 lactose Substances 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
125000000896 monocarboxylic acid group Chemical group 0.000 description 4
230000007935 neutral effect Effects 0.000 description 4
150000002825 nitriles Chemical class 0.000 description 4
239000002504 physiological saline solution Substances 0.000 description 4
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
230000002829 reductive effect Effects 0.000 description 4
239000011780 sodium chloride Substances 0.000 description 4
238000005406 washing Methods 0.000 description 4
238000010626 work up procedure Methods 0.000 description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
102000004300 GABA-A Receptors Human genes 0.000 description 3
108090000839 GABA-A Receptors Proteins 0.000 description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
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 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 3
150000008064 anhydrides Chemical class 0.000 description 3
239000002249 anxiolytic agent Substances 0.000 description 3
229910052786 argon Inorganic materials 0.000 description 3
230000006399 behavior Effects 0.000 description 3
125000001309 chloro group Chemical group Cl* 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
238000010790 dilution Methods 0.000 description 3
239000012895 dilution Substances 0.000 description 3
239000012065 filter cake Substances 0.000 description 3
125000005843 halogen group Chemical group 0.000 description 3
239000012442 inert solvent Substances 0.000 description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 3
230000004899 motility Effects 0.000 description 3
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
239000012071 phase Substances 0.000 description 3
229920000137 polyphosphoric acid Polymers 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
210000004129 prosencephalon Anatomy 0.000 description 3
230000035484 reaction time Effects 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
150000003839 salts Chemical class 0.000 description 3
239000011734 sodium Substances 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
DAPZVPLVUVKDIF-UHFFFAOYSA-N 1-ethyl-9h-pyrido[3,4-b]indole-3-carboxylic acid Chemical compound C12=CC=CC=C2NC2=C1C=C(C(O)=O)N=C2CC DAPZVPLVUVKDIF-UHFFFAOYSA-N 0.000 description 2
VGUWZCUCNQXGBU-UHFFFAOYSA-N 3-[(4-methylpiperazin-1-yl)methyl]-5-nitro-1h-indole Chemical compound C1CN(C)CCN1CC1=CNC2=CC=C([N+]([O-])=O)C=C12 VGUWZCUCNQXGBU-UHFFFAOYSA-N 0.000 description 2
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
DKEYKFSKWICGPE-UHFFFAOYSA-N 4-methyl-9h-pyrido[3,4-b]indole Chemical compound N1C2=CC=CC=C2C2=C1C=NC=C2C DKEYKFSKWICGPE-UHFFFAOYSA-N 0.000 description 2
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HAALEGHKFNLVET-AWEZNQCLSA-N ethyl (2s)-2-formamido-3-(6-methoxy-1h-indol-3-yl)propanoate Chemical compound COC1=CC=C2C(C[C@@H](C(=O)OCC)NC=O)=CNC2=C1 HAALEGHKFNLVET-AWEZNQCLSA-N 0.000 description 1
HLVKFBNRRHBJJF-UHFFFAOYSA-N ethyl 1-methyl-9h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C12=CC=CC=C2NC2=C1C=C(C(=O)OCC)N=C2C HLVKFBNRRHBJJF-UHFFFAOYSA-N 0.000 description 1
BNIFBESOTKDYSS-UHFFFAOYSA-N ethyl 4-methyl-6-nitro-9h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1=C([N+]([O-])=O)C=C2C3=C(C)C(C(=O)OCC)=NC=C3NC2=C1 BNIFBESOTKDYSS-UHFFFAOYSA-N 0.000 description 1
NZCQKMJJZUJUAW-UHFFFAOYSA-N ethyl 4-methyl-9h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1=CC=C2C3=C(C)C(C(=O)OCC)=NC=C3NC2=C1 NZCQKMJJZUJUAW-UHFFFAOYSA-N 0.000 description 1
ZRHXBQAWYYDLAR-UHFFFAOYSA-N ethyl 5-methyl-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C2=CC=CC(C)=C2C2=C1CNC(C(=O)OCC)C2 ZRHXBQAWYYDLAR-UHFFFAOYSA-N 0.000 description 1
JJWOXEAHXFQYBD-UHFFFAOYSA-N ethyl 6,8-dibromo-4-ethyl-9h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1=C(Br)C=C2C3=C(CC)C(C(=O)OCC)=NC=C3NC2=C1Br JJWOXEAHXFQYBD-UHFFFAOYSA-N 0.000 description 1
UGKOUDHTPGVESA-UHFFFAOYSA-N ethyl 6-acetamido-4-phenyl-9h-pyrido[3,4-b]indole-3-carboxylate Chemical compound CCOC(=O)C1=NC=C2NC3=CC=C(NC(C)=O)C=C3C2=C1C1=CC=CC=C1 UGKOUDHTPGVESA-UHFFFAOYSA-N 0.000 description 1
XZFNJRASXSVQBZ-UHFFFAOYSA-N ethyl 6-amino-9h-pyrido[3,4-b]indole-3-carboxylate Chemical class N1C2=CC=C(N)C=C2C2=C1C=NC(C(=O)OCC)=C2 XZFNJRASXSVQBZ-UHFFFAOYSA-N 0.000 description 1
SGDHTISZIQQDFC-UHFFFAOYSA-N ethyl 6-bromo-9h-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C2=CC=C(Br)C=C2C2=C1C=NC(C(=O)OCC)=C2 SGDHTISZIQQDFC-UHFFFAOYSA-N 0.000 description 1
XPDKHSPNMFQRPE-UHFFFAOYSA-N ethyl 6-ethoxy-4-phenyl-9h-pyrido[3,4-b]indole-3-carboxylate Chemical compound CCOC(=O)C1=NC=C2NC3=CC=C(OCC)C=C3C2=C1C1=CC=CC=C1 XPDKHSPNMFQRPE-UHFFFAOYSA-N 0.000 description 1
VAWSUFLUAZZAJK-UHFFFAOYSA-N ethyl 6-fluoro-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C2=CC=C(F)C=C2C2=C1CNC(C(=O)OCC)C2 VAWSUFLUAZZAJK-UHFFFAOYSA-N 0.000 description 1
CCDBJMSMQUKQHL-UHFFFAOYSA-N ethyl 6-formamido-4-methyl-9h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1=C(NC=O)C=C2C3=C(C)C(C(=O)OCC)=NC=C3NC2=C1 CCDBJMSMQUKQHL-UHFFFAOYSA-N 0.000 description 1
IKBKLNWJNDQHFA-UHFFFAOYSA-N ethyl 6-nitro-9h-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C2=CC=C([N+]([O-])=O)C=C2C2=C1C=NC(C(=O)OCC)=C2 IKBKLNWJNDQHFA-UHFFFAOYSA-N 0.000 description 1
LEXWISRTZVRXFB-UHFFFAOYSA-N ethyl 7-amino-9H-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C2=CC(N)=CC=C2C2=C1C=NC(C(=O)OCC)=C2 LEXWISRTZVRXFB-UHFFFAOYSA-N 0.000 description 1
BMFYSLVIUYMWJH-UHFFFAOYSA-N ethyl 7-chloro-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C2=CC(Cl)=CC=C2C2=C1CNC(C(=O)OCC)C2 BMFYSLVIUYMWJH-UHFFFAOYSA-N 0.000 description 1
DKPIMTWKIMQQBA-UHFFFAOYSA-N ethyl 7-chloro-9h-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C2=CC(Cl)=CC=C2C2=C1C=NC(C(=O)OCC)=C2 DKPIMTWKIMQQBA-UHFFFAOYSA-N 0.000 description 1
UYWJAAPAARVZAK-UHFFFAOYSA-N ethyl 7-cyano-9h-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C2=CC(C#N)=CC=C2C2=C1C=NC(C(=O)OCC)=C2 UYWJAAPAARVZAK-UHFFFAOYSA-N 0.000 description 1
KJVOYQRUWZZXKB-UHFFFAOYSA-N ethyl 7-nitro-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C2=CC([N+]([O-])=O)=CC=C2C2=C1CNC(C(=O)OCC)C2 KJVOYQRUWZZXKB-UHFFFAOYSA-N 0.000 description 1
CWXMBDOTRNLNHF-UHFFFAOYSA-N ethyl 7-nitro-9h-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C2=CC([N+]([O-])=O)=CC=C2C2=C1C=NC(C(=O)OCC)=C2 CWXMBDOTRNLNHF-UHFFFAOYSA-N 0.000 description 1
TWZZTZOXDCMIGY-UHFFFAOYSA-N ethyl 8-chloro-9h-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C2=C(Cl)C=CC=C2C2=C1C=NC(C(=O)OCC)=C2 TWZZTZOXDCMIGY-UHFFFAOYSA-N 0.000 description 1
ZJJXFPOQIQBQHV-UHFFFAOYSA-N ethyl 8-fluoro-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C2=C(F)C=CC=C2C2=C1CNC(C(=O)OCC)C2 ZJJXFPOQIQBQHV-UHFFFAOYSA-N 0.000 description 1
QSAGFZNYPGEZQD-UHFFFAOYSA-N ethyl 8-methyl-6-nitro-9h-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C2=C(C)C=C([N+]([O-])=O)C=C2C2=C1C=NC(C(=O)OCC)=C2 QSAGFZNYPGEZQD-UHFFFAOYSA-N 0.000 description 1
230000000763 evoking effect Effects 0.000 description 1
230000007717 exclusion Effects 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
239000012467 final product Substances 0.000 description 1
230000037406 food intake Effects 0.000 description 1
235000012631 food intake Nutrition 0.000 description 1
239000012458 free base Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000003365 glass fiber Substances 0.000 description 1
230000003179 granulation Effects 0.000 description 1
238000005469 granulation Methods 0.000 description 1
LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical compound COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
230000026030 halogenation Effects 0.000 description 1
238000005658 halogenation reaction Methods 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
PSFDQSOCUJVVGF-UHFFFAOYSA-N harman Chemical compound C12=CC=CC=C2NC2=C1C=CN=C2C PSFDQSOCUJVVGF-UHFFFAOYSA-N 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
239000008240 homogeneous mixture Substances 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
230000035873 hypermotility Effects 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000011534 incubation Methods 0.000 description 1
239000008011 inorganic excipient Substances 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
239000006028 limestone Substances 0.000 description 1
239000007788 liquid Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
238000011068 loading method Methods 0.000 description 1
230000006742 locomotor activity Effects 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
239000000463 material Substances 0.000 description 1
239000012528 membrane Substances 0.000 description 1
AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 1
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 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
PWVYOURGBKLVRH-UHFFFAOYSA-N methyl 4-butyl-9h-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C2=CC=CC=C2C2=C1C=NC(C(=O)OC)=C2CCCC PWVYOURGBKLVRH-UHFFFAOYSA-N 0.000 description 1
SXAFOSCLDLYJKL-UHFFFAOYSA-N methyl 4-propan-2-yl-9h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1=CC=C2C3=C(C(C)C)C(C(=O)OC)=NC=C3NC2=C1 SXAFOSCLDLYJKL-UHFFFAOYSA-N 0.000 description 1
HGDYSQPHKPMMRB-UHFFFAOYSA-N methyl 6-methylsulfanyl-4-phenyl-9h-pyrido[3,4-b]indole-3-carboxylate Chemical compound COC(=O)C1=NC=C2NC3=CC=C(SC)C=C3C2=C1C1=CC=CC=C1 HGDYSQPHKPMMRB-UHFFFAOYSA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
238000002156 mixing Methods 0.000 description 1
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
UHNHTTIUNATJKL-UHFFFAOYSA-N n-methylmethanesulfonamide Chemical compound CNS(C)(=O)=O UHNHTTIUNATJKL-UHFFFAOYSA-N 0.000 description 1
FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
238000005121 nitriding Methods 0.000 description 1
125000000449 nitro group Chemical class [O-][N+](*)=O 0.000 description 1
229910000510 noble metal Inorganic materials 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000008012 organic excipient Substances 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
239000002245 particle Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
ISWSIDIOOBJBQZ-UHFFFAOYSA-M phenolate Chemical compound [O-]C1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-M 0.000 description 1
229940031826 phenolate Drugs 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 1
239000004033 plastic Substances 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
229920001223 polyethylene glycol 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
229910000027 potassium carbonate Inorganic materials 0.000 description 1
OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
229910052939 potassium sulfate Inorganic materials 0.000 description 1
235000011151 potassium sulphates Nutrition 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
AAZYNPCMLRQUHI-UHFFFAOYSA-N propan-2-one;2-propan-2-yloxypropane Chemical compound CC(C)=O.CC(C)OC(C)C AAZYNPCMLRQUHI-UHFFFAOYSA-N 0.000 description 1
VFAMLVMNTMPGPS-UHFFFAOYSA-N propyl 4-propyl-9h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1=CC=C2C3=C(CCC)C(C(=O)OCCC)=NC=C3NC2=C1 VFAMLVMNTMPGPS-UHFFFAOYSA-N 0.000 description 1
CCDXSDXMVXWTBG-UHFFFAOYSA-N propyl 6-bromo-4-methyl-9h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1=C(Br)C=C2C3=C(C)C(C(=O)OCCC)=NC=C3NC2=C1 CCDXSDXMVXWTBG-UHFFFAOYSA-N 0.000 description 1
BZJGPPUXSZMZNZ-UHFFFAOYSA-N propyl 6-chloro-4-phenyl-9h-pyrido[3,4-b]indole-3-carboxylate Chemical compound CCCOC(=O)C1=NC=C2NC3=CC=C(Cl)C=C3C2=C1C1=CC=CC=C1 BZJGPPUXSZMZNZ-UHFFFAOYSA-N 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
230000003236 psychic effect Effects 0.000 description 1
229940001470 psychoactive drug Drugs 0.000 description 1
239000004089 psychotropic agent Substances 0.000 description 1
150000003222 pyridines Chemical class 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
230000000284 resting effect Effects 0.000 description 1
230000033764 rhythmic process Effects 0.000 description 1
NZCRJKRKKOLAOJ-XRCRFVBUSA-N rifaximin Chemical compound OC1=C(C(O)=C2C)C3=C4N=C5C=C(C)C=CN5C4=C1NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@H](C)[C@@H](OC)\C=C\O[C@@]1(C)OC2=C3C1=O NZCRJKRKKOLAOJ-XRCRFVBUSA-N 0.000 description 1
239000011435 rock Substances 0.000 description 1
239000012266 salt solution Substances 0.000 description 1
239000000932 sedative agent Substances 0.000 description 1
230000001624 sedative effect Effects 0.000 description 1
239000013049 sediment Substances 0.000 description 1
238000000926 separation method 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
AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical class [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
235000019345 sodium thiosulphate Nutrition 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000000021 stimulant Substances 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000003826 tablet Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
238000005809 transesterification reaction Methods 0.000 description 1
230000001052 transient effect Effects 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
238000005292 vacuum distillation Methods 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
230000002618 waking effect Effects 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
- C07H13/02—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
- C07H13/10—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals directly attached to heterocyclic rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Health & Medical Sciences (AREA)
Biochemistry (AREA)
Biotechnology (AREA)
General Health & Medical Sciences (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Life Sciences & Earth Sciences (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

DD80223673A 1979-08-29 1980-08-29 Substituierte beta-carbolin-3-carbonsaeure-derivate DD152935A5 (de)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
DK362279		1979-08-29
DK88980A DK88980A (da)	1980-02-29	1980-02-29	Beta-carbonline-3-carboxylsyrederivater og fremgangsmaader til fremstilling af samme
DE19803015816 DE3015816A1 (de)	1980-04-22	1980-04-22	4-substituierte- (beta) -carbolin-3-carbonsaeurederivate, ihre herstellung und verwendung
DE19803023567 DE3023567A1 (de)	1980-06-20	1980-06-20	Substituierte (beta) -carbolin-3-carbonsaeurederivate

Publications (1)

Publication Number	Publication Date
DD152935A5 true DD152935A5 (de)	1981-12-16

Family

ID=27432526

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DD80223673A DD152935A5 (de)	1979-08-29	1980-08-29	Substituierte beta-carbolin-3-carbonsaeure-derivate

Country Status (16)

Country	Link
US (2)	US4371536A (fr)
EP (1)	EP0030254B1 (fr)
CA (1)	CA1150246A (fr)
DD (1)	DD152935A5 (fr)
DE (1)	DE3069559D1 (fr)
ES (1)	ES8106305A1 (fr)
FI (1)	FI68829C (fr)
HU (1)	HU186744B (fr)
IE (1)	IE50229B1 (fr)
IL (1)	IL60906A (fr)
NO (1)	NO155055C (fr)
NZ (1)	NZ194747A (fr)
PL (1)	PL226479A1 (fr)
PT (1)	PT71744B (fr)
RO (1)	RO80265B (fr)
YU (1)	YU215580A (fr)

Families Citing this family (38)

* Cited by examiner, † Cited by third party
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
JPS57123180A (en) *	1980-12-17	1982-07-31	Schering Ag	3-substituted beta-carboline, manufacture and psychotropic drug containing same
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
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
DK149270C (da) *	1983-05-27	1986-08-25	Schering Ag	Analogifremgangsmaade til fremstilling af beta-carbolin-3-carboxylsyrederivater
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)
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)
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
FR2555988A1 (fr) *	1983-12-06	1985-06-07	Centre Nat Rech Scient	Derive de b-carbolines, procede pour leurs preparations et medicament les contenant
DK240184D0 (da) *	1984-05-15	1984-05-15	Ferrosan As	Beta-carboline-3-carboxylic acid derivatives and method of preparing the same
DE3535928A1 (de) *	1985-10-04	1987-04-09	Schering Ag	Tetrahydro-(beta)-carboline, verfahren zu ihrer 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
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
WO1988002751A1 (fr) *	1986-10-13	1988-04-21	Asahi Kasei Kogyo Kabushiki Kaisha	Derives de pyridine
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
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1980
- 1980-08-22 NZ NZ194747A patent/NZ194747A/xx unknown
- 1980-08-23 EP EP80105019A patent/EP0030254B1/fr not_active Expired
- 1980-08-23 DE DE8080105019T patent/DE3069559D1/de not_active Expired
- 1980-08-25 IL IL60906A patent/IL60906A/xx unknown
- 1980-08-27 PT PT71744A patent/PT71744B/pt unknown
- 1980-08-27 RO RO102050A patent/RO80265B/ro unknown
- 1980-08-28 YU YU02155/80A patent/YU215580A/xx unknown
- 1980-08-28 HU HU802129A patent/HU186744B/hu unknown
- 1980-08-28 CA CA000359184A patent/CA1150246A/fr not_active Expired
- 1980-08-28 FI FI802720A patent/FI68829C/fi not_active IP Right Cessation
- 1980-08-28 NO NO802546A patent/NO155055C/no unknown
- 1980-08-28 US US06/182,244 patent/US4371536A/en not_active Expired - Lifetime
- 1980-08-28 IE IE1806/80A patent/IE50229B1/en not_active IP Right Cessation
- 1980-08-29 ES ES494590A patent/ES8106305A1/es not_active Expired
- 1980-08-29 PL PL22647980A patent/PL226479A1/xx unknown
- 1980-08-29 DD DD80223673A patent/DD152935A5/de unknown
1988
- 1988-04-25 US US07/188,145 patent/US5010077A/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
NO155055C (no)	1987-02-04
NO155055B (no)	1986-10-27
FI68829C (fi)	1985-11-11
EP0030254A1 (fr)	1981-06-17
RO80265A (fr)	1983-04-29
US4371536A (en)	1983-02-01
CA1150246A (fr)	1983-07-19
ES494590A0 (es)	1981-08-16
PL226479A1 (fr)	1981-10-30
NO802546L (no)	1981-03-02
PT71744B (en)	1981-06-08
US5010077A (en)	1991-04-23
DE3069559D1 (en)	1984-12-06
IE801806L (en)	1981-02-28
HU186744B (en)	1985-09-30
PT71744A (en)	1980-09-01
IE50229B1 (en)	1986-03-05
IL60906A (en)	1985-11-29
RO80265B (ro)	1983-04-30
EP0030254B1 (fr)	1984-10-31
FI802720A7 (fi)	1981-03-01
IL60906A0 (en)	1980-10-26
FI68829B (fi)	1985-07-31
ES8106305A1 (es)	1981-08-16
YU215580A (en)	1984-02-29
NZ194747A (en)	1988-11-29

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