DK166496B1 - Amino-5,6,7,8-tetrahydronaphthooe2,3-baafuranderivater og fremgangsmaade til deres fremstilling - Google Patents

Amino-5,6,7,8-tetrahydronaphthooe2,3-baafuranderivater og fremgangsmaade til deres fremstilling Download PDF

Info

Publication number: DK166496B1
Authority: DK; Denmark
Prior art keywords: radical; general formula; formula; furan; hexahydronaphtho
Prior art date: 1987-04-01

Application number

DK178488A

Other languages

Danish (da)

English (en)

Other versions

DK178488A (da

DK178488D0 (da

Inventor

Jean-Louis Peglion

Jean-Claude Poignant

Joel Vian

Original Assignee

Adir

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.)

1987-04-01

Filing date

1988-03-30

Publication date

1993-06-01

1988-03-30 Application filed by Adir filed Critical Adir

1988-03-30 Publication of DK178488D0 publication Critical patent/DK178488D0/da

1988-10-02 Publication of DK178488A publication Critical patent/DK178488A/da

1993-06-01 Application granted granted Critical

1993-06-01 Publication of DK166496B1 publication Critical patent/DK166496B1/da

Links

238000000034 method Methods 0.000 title claims description 30
238000002360 preparation method Methods 0.000 title claims description 7
150000001875 compounds Chemical class 0.000 claims abstract description 147
-1 alkyl radical Chemical class 0.000 claims abstract description 83
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 70
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 55
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 40
MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims abstract description 11
SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 claims abstract description 9
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 6
ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical compound O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims abstract description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 3
229910052760 oxygen Inorganic materials 0.000 claims abstract description 3
239000001301 oxygen Substances 0.000 claims abstract description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 99
239000002904 solvent Substances 0.000 claims description 26
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 24
150000003839 salts Chemical class 0.000 claims description 20
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 18
230000000694 effects Effects 0.000 claims description 18
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 18
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 15
150000007522 mineralic acids Chemical class 0.000 claims description 15
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 14
150000007524 organic acids Chemical class 0.000 claims description 14
239000003960 organic solvent Substances 0.000 claims description 14
230000002378 acidificating effect Effects 0.000 claims description 13
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 12
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
229910052739 hydrogen Inorganic materials 0.000 claims description 12
239000002585 base Substances 0.000 claims description 11
239000001257 hydrogen Substances 0.000 claims description 11
239000012279 sodium borohydride Substances 0.000 claims description 11
229910000033 sodium borohydride Inorganic materials 0.000 claims description 11
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 10
230000029936 alkylation Effects 0.000 claims description 10
238000005804 alkylation reaction Methods 0.000 claims description 10
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 10
150000003335 secondary amines Chemical class 0.000 claims description 10
150000003512 tertiary amines Chemical class 0.000 claims description 10
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 9
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 9
238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 9
235000019253 formic acid Nutrition 0.000 claims description 9
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
230000001476 alcoholic effect Effects 0.000 claims description 8
238000006243 chemical reaction Methods 0.000 claims description 8
150000007529 inorganic bases Chemical class 0.000 claims description 8
230000003287 optical effect Effects 0.000 claims description 8
229910052763 palladium Inorganic materials 0.000 claims description 8
150000003254 radicals Chemical class 0.000 claims description 8
AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 claims description 8
HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 claims description 6
239000007868 Raney catalyst Substances 0.000 claims description 6
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims description 6
229910000564 Raney nickel Inorganic materials 0.000 claims description 6
150000001351 alkyl iodides Chemical class 0.000 claims description 6
150000002443 hydroxylamines Chemical class 0.000 claims description 6
229910052987 metal hydride Inorganic materials 0.000 claims description 6
150000004681 metal hydrides Chemical class 0.000 claims description 6
WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 claims description 6
VDCLSGXZVUDARN-UHFFFAOYSA-N molecular bromine;pyridine;hydrobromide Chemical compound Br.BrBr.C1=CC=NC=C1 VDCLSGXZVUDARN-UHFFFAOYSA-N 0.000 claims description 6
GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 claims description 6
239000011701 zinc Substances 0.000 claims description 6
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 5
LWJROJCJINYWOX-UHFFFAOYSA-L mercury dichloride Chemical compound Cl[Hg]Cl LWJROJCJINYWOX-UHFFFAOYSA-L 0.000 claims description 5
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims description 5
229910052725 zinc Inorganic materials 0.000 claims description 5
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 claims description 4
CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 4
AYLIEDQYYJIGDP-UHFFFAOYSA-N [C]1=CC=CS1 Chemical compound [C]1=CC=CS1 AYLIEDQYYJIGDP-UHFFFAOYSA-N 0.000 claims description 4
239000002253 acid Substances 0.000 claims description 4
239000012298 atmosphere Substances 0.000 claims description 4
ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 claims description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
229910001641 magnesium iodide Inorganic materials 0.000 claims description 4
229960002523 mercuric chloride Drugs 0.000 claims description 4
LHPRFHWNVYOELH-UHFFFAOYSA-N n-(3,5,6,7-tetrahydro-2h-benzo[f][1]benzofuran-8-ylidene)hydroxylamine Chemical compound C1=C2C(=NO)CCCC2=CC2=C1OCC2 LHPRFHWNVYOELH-UHFFFAOYSA-N 0.000 claims description 4
239000003495 polar organic solvent Substances 0.000 claims description 4
XIWUXJWOADJVCB-UHFFFAOYSA-N 2,3,5,6,7,8-hexahydrobenzo[f][1]benzofuran-6-amine Chemical compound C1=C2CC(N)CCC2=CC2=C1CCO2 XIWUXJWOADJVCB-UHFFFAOYSA-N 0.000 claims description 3
FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 claims description 3
IGONCCSQFTXEHV-UHFFFAOYSA-N 3,5,6,7-tetrahydro-2h-benzo[f][1]benzofuran-8-one Chemical compound C1=C2C(=O)CCCC2=CC2=C1OCC2 IGONCCSQFTXEHV-UHFFFAOYSA-N 0.000 claims description 3
PVDAXUSZNHTCHH-UHFFFAOYSA-N 4-(2,3-dihydro-1-benzofuran-5-yl)butanoic acid Chemical compound OC(=O)CCCC1=CC=C2OCCC2=C1 PVDAXUSZNHTCHH-UHFFFAOYSA-N 0.000 claims description 3
VQXDQAATJUJGME-UHFFFAOYSA-N 5,6,7,8-tetrahydrobenzo[f][1]benzofuran-2-amine Chemical class C1CCCC2=C1C=C1C=C(N)OC1=C2 VQXDQAATJUJGME-UHFFFAOYSA-N 0.000 claims description 3
GJWRJDBPEUJXBA-UHFFFAOYSA-N 6-azido-2,3,5,6,7,8-hexahydrobenzo[f][1]benzofuran Chemical class C1=C2CC(N=[N+]=[N-])CCC2=CC2=C1CCO2 GJWRJDBPEUJXBA-UHFFFAOYSA-N 0.000 claims description 3
229910000497 Amalgam Inorganic materials 0.000 claims description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 3
RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 claims description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 3
239000003153 chemical reaction reagent Substances 0.000 claims description 3
238000005984 hydrogenation reaction Methods 0.000 claims description 3
NRUWWBCNUPJFMF-UHFFFAOYSA-N n-(3-oxo-5,6,7,8-tetrahydrobenzo[f][1]benzofuran-7-yl)acetamide Chemical compound C1=C2CC(NC(=O)C)CCC2=CC2=C1OCC2=O NRUWWBCNUPJFMF-UHFFFAOYSA-N 0.000 claims description 3
125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
229940014800 succinic anhydride Drugs 0.000 claims description 3
DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims description 2
GRQZAOLHWNQTEQ-UHFFFAOYSA-N 2,3,5,6,7,8-hexahydrobenzo[f][1]benzofuran-5-amine Chemical compound C1=C2C(N)CCCC2=CC2=C1CCO2 GRQZAOLHWNQTEQ-UHFFFAOYSA-N 0.000 claims description 2
PPKHAIRFQKFMLE-UHFFFAOYSA-N 2,7-dimethoxynaphthalene Chemical compound C1=CC(OC)=CC2=CC(OC)=CC=C21 PPKHAIRFQKFMLE-UHFFFAOYSA-N 0.000 claims description 2
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 2
UPLMJDIRMLDPAV-UHFFFAOYSA-N 3,6,7,8-tetrahydro-2h-benzo[f][1]benzofuran-5-one Chemical compound C1=C2C(=O)CCCC2=CC2=C1CCO2 UPLMJDIRMLDPAV-UHFFFAOYSA-N 0.000 claims description 2
PSBMHECNJWGCHX-UHFFFAOYSA-N 4-(2,3-dihydro-1-benzofuran-5-yl)-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)C1=CC=C2OCCC2=C1 PSBMHECNJWGCHX-UHFFFAOYSA-N 0.000 claims description 2
CDIIZULDSLKBKV-UHFFFAOYSA-N 4-chlorobutanoyl chloride Chemical compound ClCCCC(Cl)=O CDIIZULDSLKBKV-UHFFFAOYSA-N 0.000 claims description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 claims description 2
JGLQWTADIHKLMX-UHFFFAOYSA-N 5,6,7,8-tetrahydrobenzo[f][1]benzofuran-7-amine Chemical compound C1=C2CC(N)CCC2=CC2=C1OC=C2 JGLQWTADIHKLMX-UHFFFAOYSA-N 0.000 claims description 2
ZNWNWWLWFCCREO-UHFFFAOYSA-N 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C1CC(N)CC2=CC(OC)=CC=C21 ZNWNWWLWFCCREO-UHFFFAOYSA-N 0.000 claims description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 2
238000005903 acid hydrolysis reaction Methods 0.000 claims description 2
229910021529 ammonia Inorganic materials 0.000 claims description 2
239000003849 aromatic solvent Substances 0.000 claims description 2
238000005893 bromination reaction Methods 0.000 claims description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
229910052794 bromium Inorganic materials 0.000 claims description 2
125000001246 bromo group Chemical group Br* 0.000 claims description 2
238000009833 condensation Methods 0.000 claims description 2
230000005494 condensation Effects 0.000 claims description 2
PSMFGSXWIXKVRU-UHFFFAOYSA-N n-(2,3,5,6,7,8-hexahydrobenzo[f][1]benzofuran-7-yl)acetamide Chemical compound C1=C2CC(NC(=O)C)CCC2=CC2=C1OCC2 PSMFGSXWIXKVRU-UHFFFAOYSA-N 0.000 claims description 2
UMMUFPYYVNYMNR-UHFFFAOYSA-N n-(5,6,7,8-tetrahydrobenzo[f][1]benzofuran-7-yl)acetamide Chemical compound C1=C2CC(NC(=O)C)CCC2=CC2=C1OC=C2 UMMUFPYYVNYMNR-UHFFFAOYSA-N 0.000 claims description 2
KYSJXDTUXLCEMC-UHFFFAOYSA-N n-(7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)acetamide Chemical compound C1=C(O)C=C2CC(NC(=O)C)CCC2=C1 KYSJXDTUXLCEMC-UHFFFAOYSA-N 0.000 claims description 2
NEMOWGVHPDJJRU-UHFFFAOYSA-N n-(7-methoxy-3,4-dihydro-1h-naphthalen-2-ylidene)hydroxylamine Chemical compound C1CC(=NO)CC2=CC(OC)=CC=C21 NEMOWGVHPDJJRU-UHFFFAOYSA-N 0.000 claims description 2
AFDMODCXODAXLC-UHFFFAOYSA-N phenylmethanimine Chemical compound N=CC1=CC=CC=C1 AFDMODCXODAXLC-UHFFFAOYSA-N 0.000 claims description 2
229920000137 polyphosphoric acid Polymers 0.000 claims description 2
150000003141 primary amines Chemical class 0.000 claims description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 claims description 2
FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 claims description 2
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 claims 2
QAVVAJPBMBJOAU-UHFFFAOYSA-N 2,3,5,6,7,8-hexahydrobenzo[f][1]benzofuran-8-amine Chemical compound C1=C2C(N)CCCC2=CC2=C1OCC2 QAVVAJPBMBJOAU-UHFFFAOYSA-N 0.000 claims 1
FMTRDUHECKQNOV-UHFFFAOYSA-N 7,7-dibromo-2,3,5,6-tetrahydrobenzo[f][1]benzofuran-8-one Chemical compound C1=C2C(=O)C(Br)(Br)CCC2=CC2=C1OCC2 FMTRDUHECKQNOV-UHFFFAOYSA-N 0.000 claims 1
IKJGRQHLMIQVCA-UHFFFAOYSA-N C1=C2C(=NO)CCCC2=CC2=C1CCO2 Chemical compound C1=C2C(=NO)CCCC2=CC2=C1CCO2 IKJGRQHLMIQVCA-UHFFFAOYSA-N 0.000 claims 1
150000002240 furans Chemical class 0.000 claims 1
QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 claims 1
229910052753 mercury Inorganic materials 0.000 claims 1
YLSJLYYBVHQMEQ-UHFFFAOYSA-N n-(7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)acetamide Chemical compound C1CC(NC(C)=O)CC2=CC(OC)=CC=C21 YLSJLYYBVHQMEQ-UHFFFAOYSA-N 0.000 claims 1
230000001430 anti-depressive effect Effects 0.000 abstract description 6
230000003291 dopaminomimetic effect Effects 0.000 abstract description 6
239000000935 antidepressant agent Substances 0.000 abstract description 5
229940005513 antidepressants Drugs 0.000 abstract description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 5
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 96
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 82
238000002844 melting Methods 0.000 description 56
230000008018 melting Effects 0.000 description 56
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 56
239000000203 mixture Substances 0.000 description 53
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 51
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 50
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 44
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
239000000243 solution Substances 0.000 description 32
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
238000001704 evaporation Methods 0.000 description 22
230000008020 evaporation Effects 0.000 description 22
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
239000012074 organic phase Substances 0.000 description 21
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
238000010992 reflux Methods 0.000 description 16
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 14
229910000041 hydrogen chloride Inorganic materials 0.000 description 13
239000012429 reaction media Substances 0.000 description 13
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
230000008485 antagonism Effects 0.000 description 12
239000012071 phase Substances 0.000 description 12
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
239000000047 product Substances 0.000 description 10
238000003756 stirring Methods 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
241001465754 Metazoa Species 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 9
229960004046 apomorphine Drugs 0.000 description 9
238000001914 filtration Methods 0.000 description 9
239000002244 precipitate Substances 0.000 description 9
241000700159 Rattus Species 0.000 description 8
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
230000002631 hypothermal effect Effects 0.000 description 8
238000001556 precipitation Methods 0.000 description 8
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 7
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
238000001816 cooling Methods 0.000 description 7
230000005764 inhibitory process Effects 0.000 description 6
230000000144 pharmacologic effect Effects 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 6
238000001953 recrystallisation Methods 0.000 description 6
238000012360 testing method Methods 0.000 description 6
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
241000699670 Mus sp. Species 0.000 description 5
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
239000008346 aqueous phase Substances 0.000 description 5
238000001035 drying Methods 0.000 description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
238000000926 separation method Methods 0.000 description 5
239000000377 silicon dioxide Substances 0.000 description 5
229910000029 sodium carbonate Inorganic materials 0.000 description 5
KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 4
QFCRKCGTAXXTIV-UHFFFAOYSA-N 2,3,5,6,7,8-hexahydrobenzo[f][1]benzofuran-7-amine Chemical compound C1=C2CC(N)CCC2=CC2=C1OCC2 QFCRKCGTAXXTIV-UHFFFAOYSA-N 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
230000016571 aggressive behavior Effects 0.000 description 4
150000001408 amides Chemical class 0.000 description 4
229940025084 amphetamine Drugs 0.000 description 4
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
239000003814 drug Substances 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
150000003840 hydrochlorides Chemical class 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
CUHWEIYCZBDZQZ-UHFFFAOYSA-N uranium hydrochloride Chemical compound Cl.[U] CUHWEIYCZBDZQZ-UHFFFAOYSA-N 0.000 description 4
DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 3
RJDYPHZMWUEXBJ-UHFFFAOYSA-N 2,3,5,6,7,8-hexahydrobenzo[f][1]benzofuran Chemical compound C1CCCC2=C1C=C1CCOC1=C2 RJDYPHZMWUEXBJ-UHFFFAOYSA-N 0.000 description 3
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 3
QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 3
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 3
230000002539 anti-aggressive effect Effects 0.000 description 3
NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 3
239000003054 catalyst Substances 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
229940079593 drug Drugs 0.000 description 3
239000008098 formaldehyde solution Substances 0.000 description 3
VXAOKODLROCQJS-UHFFFAOYSA-N furan;hydrochloride Chemical compound Cl.C=1C=COC=1 VXAOKODLROCQJS-UHFFFAOYSA-N 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
QEVHRUUCFGRFIF-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C(C5=CC=C(OC)C=C5N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 QEVHRUUCFGRFIF-MDEJGZGSSA-N 0.000 description 3
229960003147 reserpine Drugs 0.000 description 3
MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 3
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
239000000725 suspension Substances 0.000 description 3
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
206010001488 Aggression Diseases 0.000 description 2
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
238000005481 NMR spectroscopy Methods 0.000 description 2
UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
241000220317 Rosa Species 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
208000012761 aggressive behavior Diseases 0.000 description 2
230000006399 behavior Effects 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
201000010099 disease Diseases 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
229960003638 dopamine Drugs 0.000 description 2
239000003480 eluent Substances 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
YEBVZCIKZSZGIS-UHFFFAOYSA-N ethyl 6-bromoheptanoate Chemical compound CCOC(=O)CCCCC(C)Br YEBVZCIKZSZGIS-UHFFFAOYSA-N 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
238000000605 extraction Methods 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
150000002431 hydrogen Chemical class 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
229910052943 magnesium sulfate Inorganic materials 0.000 description 2
235000019341 magnesium sulphate Nutrition 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
238000005259 measurement Methods 0.000 description 2
230000007935 neutral effect Effects 0.000 description 2
150000002923 oximes Chemical class 0.000 description 2
239000008177 pharmaceutical agent Substances 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
239000011734 sodium Substances 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
238000005406 washing Methods 0.000 description 2
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
YONLFQNRGZXBBF-KBPBESRZSA-N (2s,3s)-2,3-dibenzoyloxybutanedioic acid Chemical compound O([C@H](C(=O)O)[C@H](OC(=O)C=1C=CC=CC=1)C(O)=O)C(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-KBPBESRZSA-N 0.000 description 1
MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
JRZGPXSSNPTNMA-UHFFFAOYSA-N 1,2,3,4-tetrahydronaphthalen-1-amine Chemical compound C1=CC=C2C(N)CCCC2=C1 JRZGPXSSNPTNMA-UHFFFAOYSA-N 0.000 description 1
MMYKTRPLXXWLBC-UHFFFAOYSA-N 1-bromo-2-ethoxyethane Chemical compound CCOCCBr MMYKTRPLXXWLBC-UHFFFAOYSA-N 0.000 description 1
KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 1
KCKZIWSINLBROE-UHFFFAOYSA-N 3,4-dihydro-1h-naphthalen-2-one Chemical compound C1=CC=C2CC(=O)CCC2=C1 KCKZIWSINLBROE-UHFFFAOYSA-N 0.000 description 1
XRFHMPLYICOBHE-UHFFFAOYSA-N 6,6-dibromo-2,3,7,8-tetrahydrobenzo[f][1]benzofuran-5-one Chemical compound C1=C2C(=O)C(Br)(Br)CCC2=CC2=C1CCO2 XRFHMPLYICOBHE-UHFFFAOYSA-N 0.000 description 1
PMDGEWIIUMXOPP-UHFFFAOYSA-N 6,7,8,9-tetrahydro-1h-benzo[g]indol-8-amine Chemical class C1=C2C=CNC2=C2CC(N)CCC2=C1 PMDGEWIIUMXOPP-UHFFFAOYSA-N 0.000 description 1
FZOSVIKAGWKCBU-UHFFFAOYSA-N 6,7,8,9-tetrahydrobenzo[g][1]benzofuran-8-amine Chemical compound C1=C2C=COC2=C2CC(N)CCC2=C1 FZOSVIKAGWKCBU-UHFFFAOYSA-N 0.000 description 1
FEWJVDPHOBWQGC-UHFFFAOYSA-N 6-azido-2,3,5,6,7,8-hexahydrobenzo[f][1]benzofuran-5-ol Chemical compound C1=C2C(O)C(N=[N+]=[N-])CCC2=CC2=C1CCO2 FEWJVDPHOBWQGC-UHFFFAOYSA-N 0.000 description 1
GDIHDQJNMDGZOS-UHFFFAOYSA-N 6-bromo-6-methyl-2,3,7,8-tetrahydrobenzo[f][1]benzofuran-5-one Chemical compound C1=C2C(=O)C(C)(Br)CCC2=CC2=C1CCO2 GDIHDQJNMDGZOS-UHFFFAOYSA-N 0.000 description 1
WIMDAZKUTWUIBG-UHFFFAOYSA-N 7,8,9,10-tetrahydrobenzo[h]quinolin-9-amine Chemical class C1=CC=NC2=C(CC(N)CC3)C3=CC=C21 WIMDAZKUTWUIBG-UHFFFAOYSA-N 0.000 description 1
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
241000557626 Corvus corax Species 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
208000001287 Galactorrhea Diseases 0.000 description 1
206010017600 Galactorrhoea Diseases 0.000 description 1
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 1
238000012404 In vitro experiment Methods 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
241000699666 Mus <mouse, genus> Species 0.000 description 1
102100026933 Myelin-associated neurite-outgrowth inhibitor Human genes 0.000 description 1
YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 1
102000003946 Prolactin Human genes 0.000 description 1
108010057464 Prolactin Proteins 0.000 description 1
206010042008 Stereotypy Diseases 0.000 description 1
STSCVKRWJPWALQ-UHFFFAOYSA-N TRIFLUOROACETIC ACID ETHYL ESTER Chemical compound CCOC(=O)C(F)(F)F STSCVKRWJPWALQ-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
241000906446 Theraps Species 0.000 description 1
DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
239000000556 agonist Substances 0.000 description 1
230000001270 agonistic effect Effects 0.000 description 1
BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
235000011114 ammonium hydroxide Nutrition 0.000 description 1
230000003321 amplification Effects 0.000 description 1
230000003542 behavioural effect Effects 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
VIHAEDVKXSOUAT-UHFFFAOYSA-N but-2-en-4-olide Chemical compound O=C1OCC=C1 VIHAEDVKXSOUAT-UHFFFAOYSA-N 0.000 description 1
229910002091 carbon monoxide Inorganic materials 0.000 description 1
210000005056 cell body Anatomy 0.000 description 1
229940125890 compound Ia Drugs 0.000 description 1
WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
229960001270 d- tartaric acid Drugs 0.000 description 1
230000007812 deficiency Effects 0.000 description 1
238000011161 development Methods 0.000 description 1
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 1
238000007865 diluting Methods 0.000 description 1
238000009826 distribution Methods 0.000 description 1
229940052760 dopamine agonists Drugs 0.000 description 1
239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
239000008298 dragée Substances 0.000 description 1
239000012156 elution solvent Substances 0.000 description 1
BUEKMBOIHDZAPT-UHFFFAOYSA-N ethyl 5-bromohexanoate Chemical compound CCOC(=O)CCCC(C)Br BUEKMBOIHDZAPT-UHFFFAOYSA-N 0.000 description 1
AENANDLBHFJSEX-UHFFFAOYSA-N ethyl 6-(2,3,5,6,7,8-hexahydrobenzo[f][1]benzofuran-7-ylamino)hexanoate Chemical compound C1=C2CC(NCCCCCC(=O)OCC)CCC2=CC2=C1OCC2 AENANDLBHFJSEX-UHFFFAOYSA-N 0.000 description 1
DXBULVYHTICWKT-UHFFFAOYSA-N ethyl 6-bromohexanoate Chemical compound CCOC(=O)CCCCCBr DXBULVYHTICWKT-UHFFFAOYSA-N 0.000 description 1
OOBFNDGMAGSNKA-UHFFFAOYSA-N ethyl 7-bromoheptanoate Chemical compound CCOC(=O)CCCCCCBr OOBFNDGMAGSNKA-UHFFFAOYSA-N 0.000 description 1
YTYSHBHYUQFTLO-UHFFFAOYSA-N ethyl 7-bromooctanoate Chemical compound CCOC(=O)CCCCCC(C)Br YTYSHBHYUQFTLO-UHFFFAOYSA-N 0.000 description 1
IXSBRLYBILQTJT-UHFFFAOYSA-N furan-3-one hydrochloride Chemical compound Cl.O=C1COC=C1 IXSBRLYBILQTJT-UHFFFAOYSA-N 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000015220 hamburgers Nutrition 0.000 description 1
229940088597 hormone Drugs 0.000 description 1
239000005556 hormone Substances 0.000 description 1
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
208000031424 hyperprolactinemia Diseases 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
238000002955 isolation Methods 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
238000012423 maintenance Methods 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
YNJSHDMKCGIMNQ-UHFFFAOYSA-N n-(3-hydroxy-2,3,5,6,7,8-hexahydrobenzo[f][1]benzofuran-7-yl)acetamide Chemical compound C1=C2CC(NC(=O)C)CCC2=CC2=C1OCC2O YNJSHDMKCGIMNQ-UHFFFAOYSA-N 0.000 description 1
PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
230000001722 neurochemical effect Effects 0.000 description 1
208000015122 neurodegenerative disease Diseases 0.000 description 1
238000003199 nucleic acid amplification method Methods 0.000 description 1
235000016709 nutrition Nutrition 0.000 description 1
230000035764 nutrition Effects 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
239000002504 physiological saline solution Substances 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
238000012545 processing Methods 0.000 description 1
229940097325 prolactin Drugs 0.000 description 1
235000019260 propionic acid Nutrition 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
230000028327 secretion Effects 0.000 description 1
239000000779 smoke Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
235000009518 sodium iodide 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
238000001228 spectrum Methods 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
239000006190 sub-lingual tablet Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
238000000859 sublimation Methods 0.000 description 1
230000008022 sublimation Effects 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
239000000829 suppository Substances 0.000 description 1
238000002636 symptomatic treatment Methods 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000003826 tablet Substances 0.000 description 1
229960001367 tartaric acid Drugs 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/92—Naphthofurans; Hydrogenated naphthofurans
- 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
- 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
- A61P25/24—Antidepressants
- 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
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Life Sciences & Earth Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
General Health & Medical Sciences (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Anesthesiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Furan Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Plural Heterocyclic Compounds (AREA)
Saccharide Compounds (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

DK178488A 1987-04-01 1988-03-30 Amino-5,6,7,8-tetrahydronaphthooe2,3-baafuranderivater og fremgangsmaade til deres fremstilling DK166496B1 (da)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
FR8704551A FR2613365B1 (fr)	1987-04-01	1987-04-01	Nouveaux derives de l'amino tetrahydro-5, 6, 7, 8 naphto (2, 3b) furanne, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent
FR8704551		1987-04-01

Publications (3)

Publication Number	Publication Date
DK178488D0 DK178488D0 (da)	1988-03-30
DK178488A DK178488A (da)	1988-10-02
DK166496B1 true DK166496B1 (da)	1993-06-01

Family

ID=9349665

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DK178488A DK166496B1 (da)	1987-04-01	1988-03-30	Amino-5,6,7,8-tetrahydronaphthooe2,3-baafuranderivater og fremgangsmaade til deres fremstilling

Country Status (16)

Country	Link
US (2)	US4863951A (de)
EP (1)	EP0286516B1 (de)
JP (1)	JPH068286B2 (de)
AT (1)	ATE73790T1 (de)
AU (1)	AU602565B2 (de)
CA (1)	CA1314050C (de)
DE (1)	DE3869173D1 (de)
DK (1)	DK166496B1 (de)
ES (1)	ES2006623A6 (de)
FR (1)	FR2613365B1 (de)
GR (1)	GR1000155B (de)
IE (1)	IE61007B1 (de)
NZ (1)	NZ224099A (de)
OA (1)	OA08825A (de)
PT (1)	PT87147B (de)
ZA (1)	ZA882282B (de)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2613364B1 (fr) *	1987-04-01	1989-06-09	Adir	Nouvelles amines tricycliques derivees du tetrahydro-5, 6, 7, 8 naphto (2, 3b) dihydro-2, 3 furanne, et du tetrahydro-6, 7, 8, 9 5h-benzocyclohepta (2, 3b) dihydro-2, 3 furanne, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent
US5071875A (en) *	1989-09-25	1991-12-10	Northwestern University	Substituted 2-amidotetralins as melatonin agonists and antagonists
FR2689509B1 (fr) *	1992-04-01	1994-06-03	Adir	Nouveaux derives spiraniques du 3-amino chromane, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent.
AU679053B2 (en) *	1993-03-25	1997-06-19	Pharmacia & Upjohn Company	Indoletetralins having dopaminergic activity
CN1191243C (zh) *	1994-07-27	2005-03-02	范德比尔特大学	用作抗炎剂的二氢苯并呋喃和相关化合物
US5674891A (en) *	1994-07-27	1997-10-07	The Procter & Gamble Company	Dihydrobenzothiophene compounds useful as anti-inflammatory agents
US6071946A (en) *	1994-10-21	2000-06-06	Adir Et Compagnie	Tricyclic urea compounds
FR2725985B1 (fr) *	1994-10-21	1996-11-15	Adir	Nouveaux composes tricycliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
US5998461A (en) *	1994-10-21	1999-12-07	Adir Et Compagnie	Tricyclic amide compounds
FR2739379B1 (fr) *	1995-09-29	1997-10-24	Adir	Nouveaux composes amines de 5,6,7,8-tetrahydronaphto(2,3-b) furane et d'indano(5,6-b)furane, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent
FR2739855B1 (fr) *	1995-10-13	1997-11-14	Adir	Nouvelles amines heterocycliques tertiaires, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
US5672620A (en) *	1996-02-01	1997-09-30	The Procter & Gamble Company	Dihydrobenzofuran and related compounds useful as anti-inflammatory agents
US5684031A (en) *	1996-02-01	1997-11-04	The Procter & Gamble Company	Dihydrobenzofuran and related compounds useful as anti-inflammatory agents
DE10041478A1 (de)	2000-08-24	2002-03-14	Sanol Arznei Schwarz Gmbh	Neue pharmazeutische Zusammensetzung
DE10334187A1 (de) *	2003-07-26	2005-03-03	Schwarz Pharma Ag	Substituierte 2-Aminotetraline zur Behandlung von Depressionen
DE10334188B4 (de) *	2003-07-26	2007-07-05	Schwarz Pharma Ag	Verwendung von Rotigotin zur Behandlung von Depressionen
PT2123265E (pt) *	2008-05-23	2012-08-06	Novaera S R L	Formulações de endipaleno no tratamento da psoríase
JP5701213B2 (ja)	2008-10-10	2015-04-15	インスティチュートオブファーマコロジーアンドトキシコロジーアカデミーオブミリタリーメディカルサイエンシズピー．エル．エー．チャイナ	新規なドーパミンｄ３受容体リガンド、その調製及び使用
US9227944B2 (en)	2008-10-10	2016-01-05	Institute Of Pharmacology And Toxicology Academy Of Military Science P.L.A. China	Dopamine D3 receptor ligands and preparation and medical uses of the same
TW202220965A (zh) *	2020-08-06	2022-06-01	美商塔朵根公司	用於心理疾患或心理增強之２－胺基茚滿化合物

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1084440A (en) *	1963-12-31	1967-09-20	Upjohn Co	Improvements in or relating to (2-aminocycloalkyl) hydroquinones and the manufacturethereof
US4470990A (en) *	1983-03-14	1984-09-11	Ayerst, Mckenna & Harrison Inc.	6,7,8,9-Tetrahydronaphtho(1,2-B)furan-8-amine derivatives and their use as dopamine receptor stimulants
FR2613364B1 (fr) *	1987-04-01	1989-06-09	Adir	Nouvelles amines tricycliques derivees du tetrahydro-5, 6, 7, 8 naphto (2, 3b) dihydro-2, 3 furanne, et du tetrahydro-6, 7, 8, 9 5h-benzocyclohepta (2, 3b) dihydro-2, 3 furanne, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent

1987
- 1987-04-01 FR FR8704551A patent/FR2613365B1/fr not_active Expired
1988
- 1988-03-22 CA CA000562140A patent/CA1314050C/fr not_active Expired - Fee Related
- 1988-03-25 US US07/173,285 patent/US4863951A/en not_active Expired - Fee Related
- 1988-03-30 ZA ZA882282A patent/ZA882282B/xx unknown
- 1988-03-30 ES ES8801011A patent/ES2006623A6/es not_active Expired
- 1988-03-30 DK DK178488A patent/DK166496B1/da not_active IP Right Cessation
- 1988-03-31 JP JP63080188A patent/JPH068286B2/ja not_active Expired - Lifetime
- 1988-03-31 NZ NZ224099A patent/NZ224099A/xx unknown
- 1988-03-31 GR GR880100208A patent/GR1000155B/el unknown
- 1988-03-31 IE IE97188A patent/IE61007B1/en not_active IP Right Cessation
- 1988-03-31 EP EP88400780A patent/EP0286516B1/de not_active Expired - Lifetime
- 1988-03-31 AT AT88400780T patent/ATE73790T1/de active
- 1988-03-31 DE DE8888400780T patent/DE3869173D1/de not_active Expired - Lifetime
- 1988-03-31 OA OA59315A patent/OA08825A/xx unknown
- 1988-03-31 AU AU14049/88A patent/AU602565B2/en not_active Ceased
- 1988-03-31 PT PT87147A patent/PT87147B/pt not_active IP Right Cessation
1989
- 1989-01-27 US US07/303,545 patent/US4885373A/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
FR2613365A1 (fr)	1988-10-07
GR1000155B (el)	1991-09-27
ES2006623A6 (es)	1989-05-01
DK178488A (da)	1988-10-02
JPS63258870A (ja)	1988-10-26
PT87147B (pt)	1992-07-31
IE880971L (en)	1988-10-01
PT87147A (pt)	1988-04-01
US4863951A (en)	1989-09-05
DK178488D0 (da)	1988-03-30
IE61007B1 (en)	1994-09-07
GR880100208A (en)	1989-01-31
NZ224099A (en)	1990-05-28
US4885373A (en)	1989-12-05
EP0286516B1 (de)	1992-03-18
FR2613365B1 (fr)	1989-07-28
EP0286516A1 (de)	1988-10-12
AU602565B2 (en)	1990-10-18
CA1314050C (fr)	1993-03-02
JPH068286B2 (ja)	1994-02-02
DE3869173D1 (de)	1992-04-23
ZA882282B (en)	1988-09-22
OA08825A (fr)	1989-03-31
ATE73790T1 (de)	1992-04-15
AU1404988A (en)	1988-10-06

Legal Events

Date	Code	Title	Description
1993-06-01	B1	Patent granted (law 1993)
1999-03-08	PBP	Patent lapsed

Publication	Publication Date	Title
DK166496B1 (da)	1993-06-01	Amino-5,6,7,8-tetrahydronaphthooe2,3-baafuranderivater og fremgangsmaade til deres fremstilling
AU2020278140B2 (en)	2025-06-26	A process for the manufacture of (2S,3S,4S,5R,6S)-3,4,5- trihydroxy-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid
DK167572B1 (da)	1993-11-22	6-substituerede 4-aminotetrahydrobenzoec,daaindoler, fremgangsmaade til fremstilling heraf samt farmaceutiske praeparater indeholdende saadanne indoler
US5225409A (en)	1993-07-06	Benzoxazinone compounds
HU198030B (en)	1989-07-28	Process for production of derivatives of benzotiasole and benzotiophen and medical preparatives containing these compounds as active substance
SK6202003A3 (en)	2004-05-04	Benzothiophene derivative compounds, process of the preparation and use thereof
DK154293B (da)	1988-10-31	Analogifremgangsmaade til fremstilling af 2(3h)-indoloner
HU211928A9 (en)	1996-01-29	Therapeutically useful 2-aminotetraline derivatives
HU202853B (en)	1991-04-29	Process for producing 3-aminodihydrobenzo(b)pyran and benzothiopyran derivatives and pharmaceutical compositions comprising same as active ingredient
AU602564B2 (en)	1990-10-18	New tricyclic amines derived from 2,3,5,6,7,8-hexahydronaphto(2,3-b) furan and from 2,3,6,7,8,9-hexahydro-5h-benzocyclohepta(2,3-b) furan, the processes for preparing them and the pharmaceutical compositions which contain them
US3862156A (en)	1975-01-21	4h-benzo{8 4,5{9 cyclohepta{8 1,2-6{9 thiophenes
Cortizo et al.	1991	Synthesis and antidopaminergic activity of some 3-(aminomethyl) tetralones as analogs of butyrophenone
JPH0227358B2 (de)	1990-06-15
JP2868429B2 (ja)	1999-03-10	新規アルキルアミノインダン化合物、その製造方法及びそれを含有する医薬組成物
US3010971A (en)	1961-11-28	Cyclopropylamine derivatives and processes for their preparation
IE65639B1 (en)	1995-11-15	4,5,6,7-Tetrahydrobenzimidazole derivatives and their preparation
WO2010037257A1 (zh)	2010-04-08	一类新型苯并氮杂卓类化合物及其制备方法和用途
HU193251B (en)	1987-08-28	Process for preparing indolo/4,3-a,b/-phenanthridine derivatives and pharmaceutical compositions containing such compounds
CA2047236C (en)	1997-07-22	Substituted 3-amino chromans
US5298503A (en)	1994-03-29	N-(isoquinolin-5-ylsulphonyl) azacycloalkanes
WO2001036428A1 (de)	2001-05-25	Silylated heterocyclic compounds
JPS611659A (ja)	1986-01-07	４‐［２‐（ジアルキルアミノ）エチル］イサチン
DK143752B (da)	1981-10-05	Analogifremgangsmaade til fremstilling af pyridobenzodiazepinoner eller farmakologisk acceptable salte deraf
JPH0521910B2 (de)	1993-03-25
JPS61267532A (ja)	1986-11-27	抗炎症及び抗アレルギ−化合物