JPS6147838B2 - - Google Patents

Info

Publication number: JPS6147838B2
Authority: JP; Japan
Prior art keywords: product; ethyl; melting point; quinolizidine; indolo
Prior art date: 1977-11-25
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired

Application number

JP54500118A

Other languages

English (en)

Japanese (ja)

Other versions

JPS54500053A (zh

Inventor

Andore Buza

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Ipsen Pharma SAS

Original Assignee

Societe de Conseils de Recherches et dApplications Scientifiques SCRAS SAS

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.)

1977-11-25

Filing date

1978-11-24

Publication date

1986-10-21

1978-11-24 Application filed by Societe de Conseils de Recherches et dApplications Scientifiques SCRAS SAS filed Critical Societe de Conseils de Recherches et dApplications Scientifiques SCRAS SAS

1979-11-08 Publication of JPS54500053A publication Critical patent/JPS54500053A/ja

1986-10-21 Publication of JPS6147838B2 publication Critical patent/JPS6147838B2/ja

Status Expired legal-status Critical Current

Links

YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 76
239000000047 product Substances 0.000 description 39
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 35
150000001875 compounds Chemical class 0.000 description 34
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
238000002844 melting Methods 0.000 description 29
230000008018 melting Effects 0.000 description 29
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
-1 ethoxycarbonylaminomethyl Chemical group 0.000 description 28
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 27
239000000243 solution Substances 0.000 description 27
239000000203 mixture Substances 0.000 description 25
238000004519 manufacturing process Methods 0.000 description 21
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 17
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 16
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 14
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 14
239000002904 solvent Substances 0.000 description 14
RXPRRQLKFXBCSJ-GIVPXCGWSA-N vincamine Chemical compound C1=CC=C2C(CCN3CCC4)=C5[C@@H]3[C@]4(CC)C[C@](O)(C(=O)OC)N5C2=C1 RXPRRQLKFXBCSJ-GIVPXCGWSA-N 0.000 description 14
239000011541 reaction mixture Substances 0.000 description 13
238000001704 evaporation Methods 0.000 description 11
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
150000003839 salts Chemical class 0.000 description 10
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
239000002253 acid Substances 0.000 description 9
150000001408 amides Chemical class 0.000 description 9
238000004458 analytical method Methods 0.000 description 9
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
230000008020 evaporation Effects 0.000 description 8
238000003756 stirring Methods 0.000 description 8
238000006243 chemical reaction Methods 0.000 description 7
RXPRRQLKFXBCSJ-UHFFFAOYSA-N dl-Vincamin Natural products C1=CC=C2C(CCN3CCC4)=C5C3C4(CC)CC(O)(C(=O)OC)N5C2=C1 RXPRRQLKFXBCSJ-UHFFFAOYSA-N 0.000 description 7
238000000034 method Methods 0.000 description 7
238000002360 preparation method Methods 0.000 description 7
229960002726 vincamine Drugs 0.000 description 7
OURDZMSSMGUMKR-UHFFFAOYSA-N 1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizine Chemical compound C1=CC=C2C(CCN3CCCCC33)=C3NC2=C1 OURDZMSSMGUMKR-UHFFFAOYSA-N 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
239000002585 base Substances 0.000 description 6
230000017531 blood circulation Effects 0.000 description 6
238000001816 cooling Methods 0.000 description 6
239000013078 crystal Substances 0.000 description 6
150000002148 esters Chemical class 0.000 description 6
239000012074 organic phase Substances 0.000 description 6
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
235000011121 sodium hydroxide Nutrition 0.000 description 6
229910052938 sodium sulfate Inorganic materials 0.000 description 6
235000011152 sodium sulphate Nutrition 0.000 description 6
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
125000004093 cyano group Chemical group *C#N 0.000 description 5
238000001035 drying Methods 0.000 description 5
230000000694 effects Effects 0.000 description 5
VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 5
238000010992 reflux Methods 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 description 4
239000003208 petroleum Substances 0.000 description 4
LJPZHJUSICYOIX-UHFFFAOYSA-N quinolizidine Chemical group C1CCCC2CCCCN21 LJPZHJUSICYOIX-UHFFFAOYSA-N 0.000 description 4
APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 4
FQMWCEMJFGFVRN-UHFFFAOYSA-N 2,3,4,6,7,8,9,9a-octahydro-1h-quinolizine;perchloric acid Chemical compound [O-]Cl(=O)(=O)=O.C1CCCC2CCCC[NH+]21 FQMWCEMJFGFVRN-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
230000001588 bifunctional effect Effects 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
239000000284 extract Substances 0.000 description 3
239000012467 final product Substances 0.000 description 3
239000005457 ice water Substances 0.000 description 3
239000012280 lithium aluminium hydride Substances 0.000 description 3
238000004452 microanalysis Methods 0.000 description 3
229910052757 nitrogen Inorganic materials 0.000 description 3
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 3
238000004454 trace mineral analysis Methods 0.000 description 3
DIOKNYUWXBKNEH-UHFFFAOYSA-N (1-ethyl-3,4,6,7,12,12b-hexahydro-2H-indolo[2,3-a]quinolizin-1-yl)methanamine Chemical compound C(C)C1(CCCN2CCC3=C(C12)NC1=CC=CC=C13)CN DIOKNYUWXBKNEH-UHFFFAOYSA-N 0.000 description 2
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
MZVQCMJNVPIDEA-UHFFFAOYSA-N [CH2]CN(CC)CC Chemical group [CH2]CN(CC)CC MZVQCMJNVPIDEA-UHFFFAOYSA-N 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
230000004872 arterial blood pressure Effects 0.000 description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
239000012024 dehydrating agents‎ Substances 0.000 description 2
239000003480 eluent Substances 0.000 description 2
KUFHJQFMMNBZFK-UHFFFAOYSA-N ethyl 1-ethyl-3,4,6,7,12,12b-hexahydro-2H-indolo[2,3-a]quinolizine-1-carboxylate Chemical compound C(C)C1(CCCN2CCC3=C(C12)NC1=CC=CC=C13)C(=O)OCC KUFHJQFMMNBZFK-UHFFFAOYSA-N 0.000 description 2
238000001914 filtration Methods 0.000 description 2
VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
MHCFAGZWMAWTNR-UHFFFAOYSA-M lithium perchlorate Chemical compound [Li+].[O-]Cl(=O)(=O)=O MHCFAGZWMAWTNR-UHFFFAOYSA-M 0.000 description 2
229910001486 lithium perchlorate Inorganic materials 0.000 description 2
DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 2
125000004433 nitrogen atom Chemical group N* 0.000 description 2
239000012071 phase Substances 0.000 description 2
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
230000033764 rhythmic process Effects 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
239000007787 solid Substances 0.000 description 2
239000007858 starting material Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
210000000689 upper leg Anatomy 0.000 description 2
NBOOZXVYXHATOW-UHFFFAOYSA-N 1-(1,3-benzodioxol-5-ylmethyl)piperazine Chemical compound C=1C=C2OCOC2=CC=1CN1CCNCC1 NBOOZXVYXHATOW-UHFFFAOYSA-N 0.000 description 1
UQPHNFNHAQUPFG-UHFFFAOYSA-N 1-ethyl-3,4,6,7,12,12b-hexahydro-2H-indolo[2,3-a]quinolizine-1-carboxylic acid Chemical compound C(C)C1(CCCN2CCC3=C(C12)NC1=CC=CC=C13)C(=O)O UQPHNFNHAQUPFG-UHFFFAOYSA-N 0.000 description 1
MOTOAJXWIMNNGV-UHFFFAOYSA-N 2-(1h-indol-3-yl)ethanamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1.C1=CC=C2C(CCN)=CNC2=C1 MOTOAJXWIMNNGV-UHFFFAOYSA-N 0.000 description 1
BUHYMJLFRZAFBF-UHFFFAOYSA-N 3,4,5-trimethoxybenzoyl chloride Chemical compound COC1=CC(C(Cl)=O)=CC(OC)=C1OC BUHYMJLFRZAFBF-UHFFFAOYSA-N 0.000 description 1
SKPGDHHYCYKJIK-UHFFFAOYSA-N 5-chloro-2-cyano-2-ethylpentanoyl chloride Chemical compound CCC(C(Cl)=O)(C#N)CCCCl SKPGDHHYCYKJIK-UHFFFAOYSA-N 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
WZNQLNOSNCIDDT-UHFFFAOYSA-N Cl.COC=1C=C(C(=O)NCC2(CCCN3CCC4=C(C23)NC2=CC=CC=C24)CC)C=C(C1OC)OC Chemical compound Cl.COC=1C=C(C(=O)NCC2(CCCN3CCC4=C(C23)NC2=CC=CC=C24)CC)C=C(C1OC)OC WZNQLNOSNCIDDT-UHFFFAOYSA-N 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
BWSWPWLOTQQQJE-UHFFFAOYSA-N N-[(1-ethyl-3,4,6,7,12,12b-hexahydro-2H-indolo[2,3-a]quinolizin-1-yl)methyl]pentan-1-amine Chemical compound C(CCCC)NCC1(CCCN2CCC3=C(C12)NC1=CC=CC=C13)CC BWSWPWLOTQQQJE-UHFFFAOYSA-N 0.000 description 1
QUVYJMCPSPPXBA-UHFFFAOYSA-N N-[(1-ethyl-3,4,6,7,12,12b-hexahydro-2H-indolo[2,3-a]quinolizin-1-yl)methyl]pentanamide Chemical compound C(CCCC)(=O)NCC1(CCCN2CCC3=C(C12)NC1=CC=CC=C13)CC QUVYJMCPSPPXBA-UHFFFAOYSA-N 0.000 description 1
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
239000003929 acidic solution Substances 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
230000036772 blood pressure Effects 0.000 description 1
230000037396 body weight Effects 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
230000002490 cerebral effect Effects 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
DMSZORWOGDLWGN-UHFFFAOYSA-N ctk1a3526 Chemical compound NP(N)(N)=O DMSZORWOGDLWGN-UHFFFAOYSA-N 0.000 description 1
238000010908 decantation Methods 0.000 description 1
230000007423 decrease Effects 0.000 description 1
YDVNLQGCLLPHAH-UHFFFAOYSA-N dichloromethane;hydrate Chemical compound O.ClCCl YDVNLQGCLLPHAH-UHFFFAOYSA-N 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
238000000921 elemental analysis Methods 0.000 description 1
239000012259 ether extract Substances 0.000 description 1
BIOLXPNWHGJRAA-UHFFFAOYSA-N ethyl 2-carbonochloridoyl-5-chloro-2-ethylpentanoate Chemical compound CCOC(=O)C(CC)(C(Cl)=O)CCCCl BIOLXPNWHGJRAA-UHFFFAOYSA-N 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
239000012458 free base Substances 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
230000000004 hemodynamic effect Effects 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
239000002198 insoluble material Substances 0.000 description 1
231100001231 less toxic Toxicity 0.000 description 1
239000007788 liquid Substances 0.000 description 1
SIAPCJWMELPYOE-UHFFFAOYSA-N lithium hydride Chemical compound [LiH] SIAPCJWMELPYOE-UHFFFAOYSA-N 0.000 description 1
229910000103 lithium hydride Inorganic materials 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
239000000463 material Substances 0.000 description 1
238000005259 measurement Methods 0.000 description 1
238000000691 measurement method Methods 0.000 description 1
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
231100001224 moderate toxicity Toxicity 0.000 description 1
UDGSVBYJWHOHNN-UHFFFAOYSA-N n',n'-diethylethane-1,2-diamine Chemical compound CCN(CC)CCN UDGSVBYJWHOHNN-UHFFFAOYSA-N 0.000 description 1
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
XGISHOFUAFNYQF-UHFFFAOYSA-N pentanoyl chloride Chemical compound CCCCC(Cl)=O XGISHOFUAFNYQF-UHFFFAOYSA-N 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
229910003446 platinum oxide Inorganic materials 0.000 description 1
239000011148 porous material Substances 0.000 description 1
239000000843 powder Substances 0.000 description 1
238000007127 saponification reaction Methods 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000820 toxicity test Toxicity 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D471/12—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 three hetero rings
- C07D471/14—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Cardiology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Heart & Thoracic Surgery (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Indole Compounds (AREA)

JP54500118A 1977-11-25 1978-11-24 Expired JPS6147838B2 (zh)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB4920177		1977-11-25
PCT/FR1978/000043 WO1979000319A1 (fr)	1977-11-25	1978-11-24	Nouvelles indolo (2, 3-a) quinolizidines, leur preparation et leur utilisation therapeutique

Publications (2)

Publication Number	Publication Date
JPS54500053A JPS54500053A (zh)	1979-11-08
JPS6147838B2 true JPS6147838B2 (zh)	1986-10-21

Family

ID=10451538

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP54500118A Expired JPS6147838B2 (zh)	1977-11-25	1978-11-24

Country Status (28)

Country	Link
JP (1)	JPS6147838B2 (zh)
AR (1)	AR218514A1 (zh)
AT (1)	AT372384B (zh)
AU (1)	AU529108B2 (zh)
BE (1)	BE872134A (zh)
CA (1)	CA1100959A (zh)
CH (1)	CH641181A5 (zh)
DE (1)	DE2851028A1 (zh)
DK (1)	DK154430C (zh)
EG (1)	EG13683A (zh)
ES (1)	ES475328A1 (zh)
FI (1)	FI64372C (zh)
FR (2)	FR2423492A1 (zh)
HK (1)	HK60884A (zh)
IE (1)	IE47518B1 (zh)
IN (1)	IN151146B (zh)
IT (1)	IT1160263B (zh)
LU (1)	LU80576A1 (zh)
MX (1)	MX5529E (zh)
MY (1)	MY8500029A (zh)
NL (1)	NL7811562A (zh)
NO (1)	NO151288C (zh)
NZ (1)	NZ188974A (zh)
PT (1)	PT68825A (zh)
SE (2)	SE431650B (zh)
SG (1)	SG61182G (zh)
WO (1)	WO1979000319A1 (zh)
ZA (1)	ZA786426B (zh)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ATE25383T1 (de) *	1981-11-18	1987-02-15	Thal Claude	Indoloquinolizinderivate, verfahren zu ihrer herstellung und ihre therapeutische anwendung.
FR2529552B1 (fr) *	1982-07-05	1985-09-27	Centre Nat Rech Scient	Nouveau procede de preparation d'intermediaires de synthese de la vindoline et intermediaires de synthese
HU191454B (en) *	1984-10-05	1987-02-27	Richter Gedeon Vegyeszeti Gyar Rt.,Hu	Process for producing amides of oktahydro-indolo/2,3-a/quinolyzin-1-yl-alkanecarboxylic acids and pharmaceutically acceptable acid additional salts thereof
HU195214B (en) *	1985-04-19	1988-04-28	Richter Gedeon Vegyeszet	Process for producing 12b-substituted-1-(hydroxymethyl)-octahydro-indolo /2,3-a/ quinolizine derivatives and pharmaceutical preparations comprising these compounds
HU194220B (en) *	1985-04-19	1988-01-28	Richter Gedeon Vegyeszet	Process for production of derivatives of 1,12 b disubstituated-octahydro-indolo /2,3-a/ quinolisine and medical compounds containing thereof
FI95572C (fi)	1987-06-22	1996-02-26	Eisai Co Ltd	Menetelmä lääkeaineena käyttökelpoisen piperidiinijohdannaisten tai sen farmaseuttisen suolan valmistamiseksi
DK0704439T3 (da) *	1993-06-18	2001-10-08	Fujisawa Pharmaceutical Co	Hidtil ukendt mellemprodukt til syntetisk anvendelse og fremgangsmåde til fremstilling af aminopiperazinderivater
FR2713644B1 (fr) *	1993-12-14	1996-02-09	Adir	Nouveaux analogues de l'éburnane, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent.
FR2713643B1 (fr) *	1993-12-14	1996-06-07	Adir	Nouveaux analogues de l'éburnane, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent.
AU2003260599A1 (en) †	2002-06-24	2004-01-06	Saint-Gobain Isover	Insulation panel for supply duct
FR2911143A1 (fr) *	2007-01-05	2008-07-11	Servier Lab	Utilisation de composes neuroprotecteurs pour l'obtention de medicaments destines au traitement de maladies neurodegeneratives.
FR2911141B1 (fr) *	2007-01-05	2009-02-20	Servier Lab	Nouveaux derives triazabenzo[a]naphtho[2,1,8-cde]azulene, leur procede de preparation et les compositions pharmaceutiques qui les contiennent.
FR2911142A1 (fr) *	2007-01-05	2008-07-11	Servier Lab	Nouveaux derives aminopyrrolo[1,2-a]indole et aminopyridazino[1,6-a]indole,leur procede de preparation et les compositions pharmaceutiques qui les contiennent.

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
HU167366B (zh) *	1972-09-06	1975-09-27
BE802387A (fr) *	1973-07-16	1973-11-16	Omnium Chimique Sa	Procede de preparation de la vincamone et de l'epi-21 vincamone a partir de la tabersonine et derives indoliques nouveaux.
HU169916B (zh) *	1974-09-27	1977-02-28
HU171165B (hu) *	1974-11-26	1977-11-28	Richter Gedeon Vegyeszet	Sposob poluchenija proizvodnykh oktagidro-indolo-skobka-2,3-a-skobka zakryta-kinolizina
FR2315277A1 (fr) *	1975-06-25	1977-01-21	Anvar	Nouveaux derives pentacycliques, leur preparation et les compositions qui les contiennent

1978
- 1978-11-15 ZA ZA00786426A patent/ZA786426B/xx unknown
- 1978-11-20 BE BE191824A patent/BE872134A/xx not_active IP Right Cessation
- 1978-11-22 NZ NZ188974A patent/NZ188974A/xx unknown
- 1978-11-23 AT AT0837478A patent/AT372384B/de active
- 1978-11-23 PT PT68825A patent/PT68825A/pt unknown
- 1978-11-23 AR AR274552A patent/AR218514A1/es active
- 1978-11-23 ES ES475328A patent/ES475328A1/es not_active Expired
- 1978-11-23 FI FI783581A patent/FI64372C/fi not_active IP Right Cessation
- 1978-11-23 AU AU41874/78A patent/AU529108B2/en not_active Expired
- 1978-11-23 NO NO783958A patent/NO151288C/no unknown
- 1978-11-24 FR FR7833175A patent/FR2423492A1/fr active Granted
- 1978-11-24 NL NL7811562A patent/NL7811562A/xx not_active Application Discontinuation
- 1978-11-24 WO PCT/FR1978/000043 patent/WO1979000319A1/fr unknown
- 1978-11-24 FR FR7833176A patent/FR2409755A1/fr active Granted
- 1978-11-24 LU LU80576A patent/LU80576A1/xx unknown
- 1978-11-24 CH CH683579A patent/CH641181A5/fr not_active IP Right Cessation
- 1978-11-24 DK DK524978A patent/DK154430C/da not_active IP Right Cessation
- 1978-11-24 IE IE2328/78A patent/IE47518B1/en unknown
- 1978-11-24 MX MX787557U patent/MX5529E/es unknown
- 1978-11-24 DE DE19782851028 patent/DE2851028A1/de active Granted
- 1978-11-24 JP JP54500118A patent/JPS6147838B2/ja not_active Expired
- 1978-11-24 IN IN851/DEL/78A patent/IN151146B/en unknown
- 1978-11-24 IT IT30171/78A patent/IT1160263B/it active
- 1978-11-24 CA CA316,809A patent/CA1100959A/en not_active Expired
- 1978-11-25 EG EG669/78A patent/EG13683A/xx active
1979
- 1979-07-23 SE SE7906287A patent/SE431650B/sv not_active IP Right Cessation
1980
- 1980-11-07 SE SE8007845A patent/SE435622B/sv not_active IP Right Cessation
1982
- 1982-12-03 SG SG611/82A patent/SG61182G/en unknown
1984
- 1984-08-02 HK HK608/84A patent/HK60884A/xx unknown
1985
- 1985-12-30 MY MY29/85A patent/MY8500029A/xx unknown

Also Published As

Publication number	Publication date
DK154430B (da)	1988-11-14
DE2851028A1 (de)	1979-05-31
MX5529E (es)	1983-09-23
FR2423492A1 (fr)	1979-11-16
FI783581A (fi)	1979-05-26
WO1979000319A1 (fr)	1979-06-14
IT7830171A0 (it)	1978-11-24
NL7811562A (nl)	1979-05-29
FR2409755B1 (zh)	1980-08-01
AU529108B2 (en)	1983-05-26
NO151288B (no)	1984-12-03
BE872134A (fr)	1979-03-16
AT372384B (de)	1983-09-26
NO783958L (no)	1979-05-28
IE47518B1 (en)	1984-04-04
SE7906287L (sv)	1979-07-23
PT68825A (en)	1978-12-01
NO151288C (no)	1985-03-13
DK154430C (da)	1989-04-17
DE2851028C2 (zh)	1990-05-03
JPS54500053A (zh)	1979-11-08
SG61182G (en)	1985-02-15
HK60884A (en)	1984-08-10
SE435622B (sv)	1984-10-08
LU80576A1 (fr)	1979-03-22
IN151146B (zh)	1983-02-26
FR2409755A1 (fr)	1979-06-22
CH641181A5 (fr)	1984-02-15
FI64372B (fi)	1983-07-29
FI64372C (fi)	1983-11-10
SE431650B (sv)	1984-02-20
AU4187478A (en)	1979-05-31
NZ188974A (en)	1989-10-27
CA1100959A (en)	1981-05-12
IE782328L (en)	1979-05-25
EG13683A (en)	1982-09-30
ES475328A1 (es)	1979-04-01
MY8500029A (en)	1985-12-31
FR2423492B1 (zh)	1980-12-05
SE8007845L (sv)	1980-11-07
AR218514A1 (es)	1980-06-13
ZA786426B (en)	1979-10-31
DK524978A (da)	1979-05-26
IT1160263B (it)	1987-03-11
ATA837478A (de)	1983-02-15

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JPH08319274A (ja)	1996-12-03	４−インドリルピペラジニル誘導体
DE3719699A1 (de)	1987-12-17	Indolderivate
JPH04279565A (ja)	1992-10-05	４−クロロ−３−スルファモイル−ｎ−（２，３−ジヒドロ−２−メチル−１ｈ−インドール−１−イル）ベンズアミドの新規な工業的製造方法
EP0021857A1 (fr)	1981-01-07	Dérivés de l'indole, leur préparation et medicaments les contenant
US4353911A (en)	1982-10-12	Indolo(2,3-a)quinolizidines, useful in increasing femoral and vertebral blood flow
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US4831167A (en)	1989-05-16	Process for diastereoselective reduction of 3-amino-1-benzoxepin-5(2H)-ones
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