CA1136629A - Octahydropyrazolo (3,4,g) quinolines - Google Patents

Octahydropyrazolo (3,4,g) quinolines

Info

Publication number: CA1136629A
Authority: CA; Canada
Prior art keywords: mixture; trans; alkyl; quinoline; octahydro
Prior art date: 1979-01-22
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

CA000379595A

Other languages

English (en)

Inventor

Edmund C. Kornfeld

Nicholas J. Bach

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.)

Eli Lilly and Co

Original Assignee

Eli Lilly and Co

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.)

1979-01-22

Filing date

1981-06-11

Publication date

1982-11-30

1979-04-19 Priority claimed from US06/031,641 external-priority patent/US4198415A/en

1981-06-11 Application filed by Eli Lilly and Co filed Critical Eli Lilly and Co

1981-06-11 Priority to CA000379595A priority Critical patent/CA1136629A/fr

1982-11-30 Application granted granted Critical

1982-11-30 Publication of CA1136629A publication Critical patent/CA1136629A/fr

Status Expired legal-status Critical Current

Links

150000003248 quinolines Chemical class 0.000 title abstract description 7
229940111121 antirheumatic drug quinolines Drugs 0.000 title abstract description 6
150000001875 compounds Chemical class 0.000 claims abstract description 75
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 46
-1 p-methoxybenzyl Chemical group 0.000 claims abstract description 32
238000000034 method Methods 0.000 claims abstract description 23
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims abstract description 21
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 20
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 12
239000002253 acid Substances 0.000 claims abstract description 11
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 9
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 7
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 7
125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims abstract description 5
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims abstract description 5
230000007062 hydrolysis Effects 0.000 claims abstract description 5
238000006460 hydrolysis reaction Methods 0.000 claims abstract description 5
125000006592 (C2-C3) alkenyl group Chemical group 0.000 claims abstract description 4
125000006593 (C2-C3) alkynyl group Chemical group 0.000 claims abstract description 4
125000006526 (C1-C2) alkyl group Chemical group 0.000 claims abstract 3
239000000126 substance Substances 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 3
239000000543 intermediate Substances 0.000 abstract description 17
102000003946 Prolactin Human genes 0.000 abstract description 14
108010057464 Prolactin Proteins 0.000 abstract description 14
229940097325 prolactin Drugs 0.000 abstract description 14
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 abstract description 7
239000003136 dopamine receptor stimulating agent Substances 0.000 abstract description 7
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 abstract description 7
238000011282 treatment Methods 0.000 abstract description 7
206010034010 Parkinsonism Diseases 0.000 abstract description 5
208000027089 Parkinsonian disease Diseases 0.000 abstract description 4
229940052760 dopamine agonists Drugs 0.000 abstract description 4
230000028327 secretion Effects 0.000 abstract description 3
230000002401 inhibitory effect Effects 0.000 abstract 1
239000000203 mixture Substances 0.000 description 99
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 80
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 78
238000006243 chemical reaction Methods 0.000 description 54
239000011541 reaction mixture Substances 0.000 description 51
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
229960001701 chloroform Drugs 0.000 description 40
238000001704 evaporation Methods 0.000 description 40
230000008020 evaporation Effects 0.000 description 40
239000000243 solution Substances 0.000 description 39
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 36
125000000217 alkyl group Chemical group 0.000 description 35
SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 34
239000002904 solvent Substances 0.000 description 31
ZMXDDKWLCZADIW-UHFFFAOYSA-N Vilsmeier-Haack reagent Natural products CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 27
239000000284 extract Substances 0.000 description 24
229920006395 saturated elastomer Polymers 0.000 description 23
150000003839 salts Chemical class 0.000 description 22
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
239000012299 nitrogen atmosphere Substances 0.000 description 21
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 18
239000011780 sodium chloride Substances 0.000 description 18
238000010992 reflux Methods 0.000 description 17
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
239000000460 chlorine Substances 0.000 description 15
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
229960000443 hydrochloric acid Drugs 0.000 description 14
235000011167 hydrochloric acid Nutrition 0.000 description 14
238000007792 addition Methods 0.000 description 13
FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 13
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
238000004809 thin layer chromatography Methods 0.000 description 12
241000700159 Rattus Species 0.000 description 11
238000004458 analytical method Methods 0.000 description 11
239000005457 ice water Substances 0.000 description 11
239000012280 lithium aluminium hydride Substances 0.000 description 11
238000002360 preparation method Methods 0.000 description 11
239000011877 solvent mixture Substances 0.000 description 11
239000000470 constituent Substances 0.000 description 10
VFICJPDIBDJAGL-UHFFFAOYSA-N (4-oxocyclohexyl) benzoate Chemical compound C=1C=CC=CC=1C(=O)OC1CCC(=O)CC1 VFICJPDIBDJAGL-UHFFFAOYSA-N 0.000 description 9
238000002844 melting Methods 0.000 description 9
230000008018 melting Effects 0.000 description 9
SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 8
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 8
229910052801 chlorine Inorganic materials 0.000 description 8
238000001816 cooling Methods 0.000 description 8
229910052739 hydrogen Inorganic materials 0.000 description 8
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical group CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
229910052794 bromium Inorganic materials 0.000 description 7
239000002026 chloroform extract Substances 0.000 description 7
238000004587 chromatography analysis Methods 0.000 description 7
WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
229910052757 nitrogen Inorganic materials 0.000 description 7
229960005419 nitrogen Drugs 0.000 description 7
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 7
229910000104 sodium hydride Inorganic materials 0.000 description 7
GRQLNUPVDJMLQN-UHFFFAOYSA-N (2-oxo-3,4,5,6,7,8-hexahydro-1h-quinolin-6-yl) benzoate Chemical compound C1CC(NC(=O)CC2)=C2CC1OC(=O)C1=CC=CC=C1 GRQLNUPVDJMLQN-UHFFFAOYSA-N 0.000 description 6
POTIYWUALSJREP-UHFFFAOYSA-N 1,2,3,4,4a,5,6,7,8,8a-decahydroquinoline Chemical compound N1CCCC2CCCCC21 POTIYWUALSJREP-UHFFFAOYSA-N 0.000 description 6
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 6
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
239000000908 ammonium hydroxide Substances 0.000 description 6
WGXZDYPGLJYBJW-UHFFFAOYSA-N chloroform;propan-2-ol Chemical compound CC(C)O.ClC(Cl)Cl WGXZDYPGLJYBJW-UHFFFAOYSA-N 0.000 description 6
239000002024 ethyl acetate extract Substances 0.000 description 6
239000012312 sodium hydride Substances 0.000 description 6
238000012360 testing method Methods 0.000 description 6
JXKJBOLPNXKPMG-UHFFFAOYSA-N 1h-pyrazolo[3,4-g]quinoline Chemical compound C1=CN=C2C=C3C=NNC3=CC2=C1 JXKJBOLPNXKPMG-UHFFFAOYSA-N 0.000 description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
101100054666 Streptomyces halstedii sch3 gene Chemical group 0.000 description 5
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 5
229940117975 chromium trioxide Drugs 0.000 description 5
GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 5
239000013078 crystal Substances 0.000 description 5
239000001257 hydrogen Substances 0.000 description 5
125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
229910052987 metal hydride Inorganic materials 0.000 description 5
150000004681 metal hydrides Chemical class 0.000 description 5
239000000047 product Substances 0.000 description 5
230000002829 reductive effect Effects 0.000 description 5
239000000725 suspension Substances 0.000 description 5
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 4
HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical class SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 4
ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
230000002378 acidificating effect Effects 0.000 description 4
ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
239000012458 free base Substances 0.000 description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
229910052740 iodine Inorganic materials 0.000 description 4
HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical class [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 description 4
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 4
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 4
238000000746 purification Methods 0.000 description 4
AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 4
238000001953 recrystallisation Methods 0.000 description 4
239000007858 starting material Substances 0.000 description 4
125000001424 substituent group Chemical group 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
101100037762 Caenorhabditis elegans rnh-2 gene Proteins 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
150000001241 acetals Chemical class 0.000 description 3
239000003929 acidic solution Substances 0.000 description 3
239000003463 adsorbent Substances 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 3
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
239000012141 concentrate Substances 0.000 description 3
230000000694 effects Effects 0.000 description 3
150000003840 hydrochlorides Chemical class 0.000 description 3
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
229910000041 hydrogen chloride Inorganic materials 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
238000007912 intraperitoneal administration Methods 0.000 description 3
239000000391 magnesium silicate Substances 0.000 description 3
229910052919 magnesium silicate Inorganic materials 0.000 description 3
235000019792 magnesium silicate Nutrition 0.000 description 3
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
239000002480 mineral oil Substances 0.000 description 3
235000010446 mineral oil Nutrition 0.000 description 3
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
239000012434 nucleophilic reagent Substances 0.000 description 3
LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
229940032330 sulfuric acid Drugs 0.000 description 3
238000005303 weighing Methods 0.000 description 3
239000011701 zinc Substances 0.000 description 3
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 2
CEKSPMMCISUSTR-UHFFFAOYSA-N 1,2,3,4,4a,5,6,7-octahydroquinoline Chemical compound C1CCC2CCCNC2=C1 CEKSPMMCISUSTR-UHFFFAOYSA-N 0.000 description 2
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
HRJMECJUZJQTNG-UHFFFAOYSA-N 4,4a,5,6,7,8,8a,9-octahydro-1h-pyrazolo[3,4-g]quinoline Chemical class C1C2CCCNC2CC2=C1NN=C2 HRJMECJUZJQTNG-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
APGZXYPWPZTKOS-UHFFFAOYSA-N 4h-pyrazolo[3,4-g]quinoline Chemical class C1=CN=C2CC3=CN=NC3=CC2=C1 APGZXYPWPZTKOS-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
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 2
229910010084 LiAlH4 Inorganic materials 0.000 description 2
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
239000012359 Methanesulfonyl chloride Substances 0.000 description 2
BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
238000005481 NMR spectroscopy Methods 0.000 description 2
229910020667 PBr3 Inorganic materials 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 2
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 2
238000002441 X-ray diffraction Methods 0.000 description 2
IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 2
239000003377 acid catalyst Substances 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
239000000556 agonist Substances 0.000 description 2
150000001299 aldehydes Chemical class 0.000 description 2
150000001350 alkyl halides Chemical class 0.000 description 2
AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
150000003863 ammonium salts Chemical class 0.000 description 2
239000002585 base Substances 0.000 description 2
229940077388 benzenesulfonate Drugs 0.000 description 2
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 2
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
238000009835 boiling Methods 0.000 description 2
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125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
UORVCLMRJXCDCP-UHFFFAOYSA-M propynoate Chemical compound [O-]C(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-M 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
BTUQCUPQFZHMNS-UHFFFAOYSA-N quinoline;dihydrochloride Chemical compound Cl.Cl.N1=CC=CC2=CC=CC=C21 BTUQCUPQFZHMNS-UHFFFAOYSA-N 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
238000011946 reduction process Methods 0.000 description 1
238000005932 reductive alkylation reaction Methods 0.000 description 1
238000006894 reductive elimination reaction Methods 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
230000007017 scission Effects 0.000 description 1
229940116351 sebacate Drugs 0.000 description 1
CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
RBWSWDPRDBEWCR-RKJRWTFHSA-N sodium;(2r)-2-[(2r)-3,4-dihydroxy-5-oxo-2h-furan-2-yl]-2-hydroxyethanolate Chemical compound [Na+].[O-]C[C@@H](O)[C@H]1OC(=O)C(O)=C1O RBWSWDPRDBEWCR-RKJRWTFHSA-N 0.000 description 1
238000012453 sprague-dawley rat model Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 0.000 description 1
ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
238000010998 test method Methods 0.000 description 1
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
229940071104 xylenesulfonate Drugs 0.000 description 1

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Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA000379595A 1979-01-22 1981-06-11 Octahydropyrazolo (3,4,g) quinolines Expired CA1136629A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000379595A CA1136629A (fr)	1979-01-22	1981-06-11	Octahydropyrazolo (3,4,g) quinolines

Applications Claiming Priority (6)

Application Number	Priority Date	Filing Date	Title
US506179A	1979-01-22	1979-01-22
US5,061		1979-01-22
US31,641		1979-04-19
US06/031,641 US4198415A (en)	1979-01-22	1979-04-19	Prolactin inhibiting octahydro pyrazolo[3,4-g]quinolines
CA000330552A CA1136140A (fr)	1979-01-22	1979-06-26	Octahydro-pyrazolo (3,4-g)-quinolines
CA000379595A CA1136629A (fr)	1979-01-22	1981-06-11	Octahydropyrazolo (3,4,g) quinolines

Publications (1)

Publication Number	Publication Date
CA1136629A true CA1136629A (fr)	1982-11-30

Family

ID=27426161

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000379595A Expired CA1136629A (fr)	1979-01-22	1981-06-11	Octahydropyrazolo (3,4,g) quinolines

Country Status (1)

Country	Link
CA (1)	CA1136629A (fr)

1981
- 1981-06-11 CA CA000379595A patent/CA1136629A/fr not_active Expired

Legal Events

Date	Code	Title	Description
1999-11-30	MKEX	Expiry

Publication	Publication Date	Title
EP0013787B1 (fr)	1984-05-02	Octahydro-pyrazolo (3,4-g)quinoléines, procédé pour leur préparation et compositions pharmaceutiques les contenant
US4166182A (en)	1979-08-28	6-n-propyl-8-methoxymethyl or methylmercaptomethylergolines and related compounds
US4235909A (en)	1980-11-25	Octahydro-2H-pyrrolo[3,4-g]quinolines
US4230861A (en)	1980-10-28	1-And/or 7-substituted-6-hydroxy (or oxo)-3-decahydroquinoline carboxylic acids
US4202979A (en)	1980-05-13	6-Ethyl(or allyl)-8-methoxymethyl or methylmercaptomethylergolines and related compounds
CA1136629A (fr)	1982-11-30	Octahydropyrazolo (3,4,g) quinolines
US4180582A (en)	1979-12-25	6-n-Propyl-8-methoxy-methyl or methylmercaptomethylergolines and related compounds as prolactin inhibitors and to treat Parkinson's syndrome
US4367231A (en)	1983-01-04	Method of using octahydro pyrazolo[3,4-g]quinolines
CA1131227A (fr)	1982-09-07	Octahydro-2h-pyrrolo (3,4-g) quinolines
CA1136141A (fr)	1982-11-23	Octahydropyrazolo (3,4,g) quinolines
CA1133487A (fr)	1982-10-12	Octahydropyrazolo (3,4,g) quinolines
CA1136144A (fr)	1982-11-23	Octahydropyrazolo (3,4,g) quinolines
EP0016274A1 (fr)	1980-10-01	2-Azaergolines et 2-aza-8(ou 9)-ergolènes, leur procédé de préparation et compositions pharmaceutiques les contenant
NZ205030A (en)	1986-03-14	Optically pure isomers of trans-1-n-propyl-6oxodecahydroquinoline
EP0172697B1 (fr)	1991-09-25	Octahydro-oxazolo[4,5-g]quinoléines
KR830000273B1 (ko)	1983-02-26	옥타하이드로 피라졸로[3,4-g]퀴놀린의 제조방법
KR830000326B1 (ko)	1983-03-04	옥타하이드로 피라졸로[3,4-g] 퀴놀린의 제조방법
US4311844A (en)	1982-01-19	Octahydro-2H-pyrrolo[3,4,-g]quinolines
CA1145750A (fr)	1983-05-03	Octahydro-2h-pyrrolo (3,4,-g) quinolines
US4282362A (en)	1981-08-04	Octahydro-2H-pyrrolo[3,4-g]quinolines
EP0142920A2 (fr)	1985-05-29	6-Oxodécahydroquinolines et procédé pour leur préparation
IE48395B1 (en)	1985-01-09	Octahydro pyrazolo(3,4-g)quinolines
KR830000586B1 (ko)	1983-03-15	옥타히드로-2H-피롤로[3, 4-g]퀴놀린의 제조방법
JPS6231717B2 (fr)	1987-07-09
FI68052B (fi)	1985-03-29	Foerfarande foer framstaellning av nya terapeutiskt anvaendbara trans-4,4a,5,6,7,8,8a,9-oktahydro-1h(och 2h)-pyrazolo-(3,4-g)kinoliner