CA1136140A - Octahydro pyrazolo (3,4,-g) quinolines - Google Patents
Octahydro pyrazolo (3,4,-g) quinolinesInfo
- Publication number
- CA1136140A CA1136140A CA000330552A CA330552A CA1136140A CA 1136140 A CA1136140 A CA 1136140A CA 000330552 A CA000330552 A CA 000330552A CA 330552 A CA330552 A CA 330552A CA 1136140 A CA1136140 A CA 1136140A
- Authority
- CA
- Canada
- Prior art keywords
- trans
- octahydro
- reacting
- pyrazolo
- quinoline
- Prior art date
- 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
Links
- 150000003248 quinolines Chemical class 0.000 title claims abstract description 8
- 229940111121 antirheumatic drug quinolines Drugs 0.000 title claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 77
- 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 claims abstract description 12
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims abstract description 12
- -1 allyl halide Chemical class 0.000 claims description 32
- 238000000034 method Methods 0.000 claims description 31
- 125000000217 alkyl group Chemical group 0.000 claims description 30
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 22
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 20
- 239000000543 intermediate Substances 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 13
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 claims description 8
- 101100054666 Streptomyces halstedii sch3 gene Chemical group 0.000 claims description 8
- 229910052987 metal hydride Inorganic materials 0.000 claims description 8
- 150000004681 metal hydrides Chemical class 0.000 claims description 8
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims description 8
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 6
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 claims description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 6
- 239000011701 zinc Substances 0.000 claims description 5
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 239000012434 nucleophilic reagent Substances 0.000 claims description 4
- LYPGDCWPTHTUDO-UHFFFAOYSA-M sodium;methanesulfinate Chemical compound [Na+].CS([O-])=O LYPGDCWPTHTUDO-UHFFFAOYSA-M 0.000 claims description 4
- 229910052725 zinc Inorganic materials 0.000 claims description 4
- VMJNTFXCTXAXTC-UHFFFAOYSA-N 2,2-difluoro-1,3-benzodioxole-5-carbonitrile Chemical group C1=C(C#N)C=C2OC(F)(F)OC2=C1 VMJNTFXCTXAXTC-UHFFFAOYSA-N 0.000 claims description 3
- 239000012359 Methanesulfonyl chloride Substances 0.000 claims description 3
- 150000001299 aldehydes Chemical class 0.000 claims description 3
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 3
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 claims description 3
- XHXXWWGGXFUMAJ-UHFFFAOYSA-N methanethiol;sodium Chemical compound [Na].SC XHXXWWGGXFUMAJ-UHFFFAOYSA-N 0.000 claims description 3
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 claims description 2
- 230000036571 hydration Effects 0.000 claims description 2
- 238000006703 hydration reaction Methods 0.000 claims description 2
- 238000005932 reductive alkylation reaction Methods 0.000 claims description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 5
- DBTDEFJAFBUGPP-UHFFFAOYSA-N Methanethial Chemical compound S=C DBTDEFJAFBUGPP-UHFFFAOYSA-N 0.000 claims 1
- 125000005037 alkyl phenyl group Chemical group 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
- PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 claims 1
- XSXHWVKGUXMUQE-UHFFFAOYSA-N osmium dioxide Inorganic materials O=[Os]=O XSXHWVKGUXMUQE-UHFFFAOYSA-N 0.000 claims 1
- 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
- 239000003136 dopamine receptor stimulating agent Substances 0.000 abstract description 9
- 238000011282 treatment Methods 0.000 abstract description 7
- 206010034010 Parkinsonism Diseases 0.000 abstract description 5
- 229940052760 dopamine agonists Drugs 0.000 abstract description 5
- 208000027089 Parkinsonian disease Diseases 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 97
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 83
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 78
- 238000006243 chemical reaction Methods 0.000 description 56
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 52
- 239000011541 reaction mixture Substances 0.000 description 49
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 44
- 229960001701 chloroform Drugs 0.000 description 42
- 238000001704 evaporation Methods 0.000 description 39
- 230000008020 evaporation Effects 0.000 description 39
- 239000000243 solution Substances 0.000 description 38
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 37
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 32
- 239000002904 solvent Substances 0.000 description 32
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- ZMXDDKWLCZADIW-UHFFFAOYSA-N Vilsmeier-Haack reagent Natural products CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
- 229920006395 saturated elastomer Polymers 0.000 description 23
- 239000000284 extract Substances 0.000 description 22
- 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
- 239000000460 chlorine Substances 0.000 description 19
- 238000010992 reflux Methods 0.000 description 19
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000011780 sodium chloride Substances 0.000 description 18
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
- 229960000443 hydrochloric acid Drugs 0.000 description 13
- 235000011167 hydrochloric acid Nutrition 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 238000004458 analytical method Methods 0.000 description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 12
- 238000004809 thin layer chromatography Methods 0.000 description 12
- 241000700159 Rattus Species 0.000 description 11
- 238000007792 addition Methods 0.000 description 11
- 239000005457 ice water Substances 0.000 description 11
- 239000012280 lithium aluminium hydride Substances 0.000 description 11
- 239000011877 solvent mixture Substances 0.000 description 11
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 10
- 238000002360 preparation method Methods 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
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 239000000470 constituent Substances 0.000 description 9
- 238000002844 melting Methods 0.000 description 9
- 230000008018 melting Effects 0.000 description 9
- 229910052794 bromium Inorganic materials 0.000 description 8
- 229910052801 chlorine Inorganic materials 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 8
- 238000001816 cooling Methods 0.000 description 7
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical group CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-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
- 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
- 239000002026 chloroform extract Substances 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 229940117975 chromium trioxide Drugs 0.000 description 6
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 6
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 239000002024 ethyl acetate extract Substances 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 239000012312 sodium hydride Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 5
- 239000000908 ammonium hydroxide Substances 0.000 description 5
- WGXZDYPGLJYBJW-UHFFFAOYSA-N chloroform;propan-2-ol Chemical compound CC(C)O.ClC(Cl)Cl WGXZDYPGLJYBJW-UHFFFAOYSA-N 0.000 description 5
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 5
- 150000002081 enamines Chemical class 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000001953 recrystallisation Methods 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
- JXKJBOLPNXKPMG-UHFFFAOYSA-N 1h-pyrazolo[3,4-g]quinoline Chemical compound C1=CN=C2C=C3C=NNC3=CC2=C1 JXKJBOLPNXKPMG-UHFFFAOYSA-N 0.000 description 4
- 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
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-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
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 239000001257 hydrogen Substances 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
- 239000007858 starting material Substances 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 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 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 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
- 239000003929 acidic solution Substances 0.000 description 3
- 239000003463 adsorbent Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 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
- 125000004435 hydrogen atom Chemical group [H]* 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
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 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
- 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
- 239000007787 solid Substances 0.000 description 3
- 229940032330 sulfuric acid Drugs 0.000 description 3
- 238000005303 weighing Methods 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
- 125000006704 (C5-C6) cycloalkyl group Chemical group 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
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 2
- 101100037762 Caenorhabditis elegans rnh-2 gene Proteins 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
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 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
- 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
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 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
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
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- 239000010452 phosphate Substances 0.000 description 1
- 229960004838 phosphoric acid Drugs 0.000 description 1
- IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
- 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
- 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
- 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
- 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
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 229940071104 xylenesulfonate Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Quinoline Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000379596A CA1136144A (en) | 1979-01-22 | 1981-06-11 | Octahydro pyrazolo (3,4,-g) quinolines |
| CA000379595A CA1136629A (en) | 1979-01-22 | 1981-06-11 | Octahydro pyrazolo (3,4,-g) quinolines |
| CA379,597A CA1133487A (en) | 1979-01-22 | 1981-06-11 | Octahydro pyrazolo (3,4-g) quinolines |
| CA000379594A CA1136141A (en) | 1979-01-22 | 1981-06-11 | Octahydro pyrazolo (3,4,-g) quinolines |
Applications Claiming Priority (4)
| 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 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1136140A true CA1136140A (en) | 1982-11-23 |
Family
ID=26673868
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000330552A Expired CA1136140A (en) | 1979-01-22 | 1979-06-26 | Octahydro pyrazolo (3,4,-g) quinolines |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US4198415A (OSRAM) |
| EP (2) | EP0013787B1 (OSRAM) |
| AT (1) | AT371819B (OSRAM) |
| AU (1) | AU528076B2 (OSRAM) |
| CA (1) | CA1136140A (OSRAM) |
| CH (3) | CH644377A5 (OSRAM) |
| DD (5) | DD148340A5 (OSRAM) |
| DE (2) | DE2966945D1 (OSRAM) |
| DK (1) | DK268879A (OSRAM) |
| EG (1) | EG14696A (OSRAM) |
| ES (4) | ES482091A1 (OSRAM) |
| FI (1) | FI65247C (OSRAM) |
| FR (5) | FR2446832A1 (OSRAM) |
| GB (4) | GB2092581A (OSRAM) |
| GR (1) | GR72516B (OSRAM) |
| IE (1) | IE48394B1 (OSRAM) |
| IL (1) | IL57668A (OSRAM) |
| LU (1) | LU81439A1 (OSRAM) |
| MY (1) | MY8500683A (OSRAM) |
| NZ (2) | NZ201279A (OSRAM) |
| PH (3) | PH14909A (OSRAM) |
| PL (4) | PL119785B1 (OSRAM) |
| PT (1) | PT69829A (OSRAM) |
| RO (2) | RO82159A (OSRAM) |
| ZA (1) | ZA793243B (OSRAM) |
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL65269A0 (en) * | 1981-03-24 | 1982-05-31 | Lilly Co Eli | 6-substituted hexahydroindazolo or hexahydroisoindolo isoquinolines |
| US4540787A (en) * | 1982-06-03 | 1985-09-10 | Eli Lilly And Company | Method of preparing trans-D1-1-alkyl-6-oxodecahydroquinolines |
| US4567266A (en) * | 1982-11-03 | 1986-01-28 | Eli Lilly And Company | Method of preparing octahydro-1H(and 2H)-pyrazolo[3,4-g]quinolines |
| US4468401A (en) * | 1982-11-03 | 1984-08-28 | Eli Lilly And Company | Method of blocking peripheral norepinephrine release |
| US4471121A (en) * | 1982-11-03 | 1984-09-11 | Eli Lilly And Company | Method of resolving trans-d alpha-1-n-propyl-6-oxodecahydroquinoline and di-p-toluoyltartaric acid salts thereof |
| ES8504174A1 (es) * | 1982-11-03 | 1985-04-16 | Lilly Co Eli | Un procedimiento para la preparacion de derivados de pirazolo-quinolinas. |
| US4647667A (en) * | 1982-11-03 | 1987-03-03 | Eli Lilly And Company | Octa- and deca-hydroquinoline intermediates |
| EP0127708B1 (en) * | 1983-06-03 | 1987-09-09 | Eli Lilly And Company | Trans-dl-1-alkyl-6-alkoxyoctahydroquinolines |
| US4626591A (en) * | 1983-08-10 | 1986-12-02 | Eli Lilly And Company | Trans-dl-1-alkyl-6-alkoxy-1,2,3,4,4a,5,8,8a octa-hydroquinolines |
| RO89126A (ro) * | 1983-09-26 | 1986-04-30 | Eli Lilly And Co,Us | Procedeu de preparare a unor derivati de chinolina |
| US4528290A (en) * | 1984-01-30 | 1985-07-09 | Eli Lilly And Company | Stimulating dopamine D-1 receptors |
| US4501890A (en) * | 1983-09-26 | 1985-02-26 | Eli Lilly And Company | Trans-(±)-2,4,6-substituted-5,5a,6,7,8,9,9a,10-octahydro-pyrimido[4,5-g]quinolines |
| IL72729A (en) * | 1983-09-26 | 1988-02-29 | Lilly Co Eli | Trans(+_)octahydropyrazole-ring alkylated pyrazoloquinolines,their preparation and pharmaceutical compositions containing them |
| US4521421A (en) * | 1983-09-26 | 1985-06-04 | Eli Lilly And Company | Treatment of sexual dysfunction |
| IL73001A0 (en) * | 1983-09-26 | 1984-12-31 | Lilly Co Eli | Improvements in and relating to 6-oxodecahydroquinolines |
| US4507478A (en) * | 1983-09-26 | 1985-03-26 | Eli Lilly And Company | 2-Mercaptopyrimidohexahydroquinolines and related compounds |
| US4587351A (en) * | 1984-04-18 | 1986-05-06 | Eli Lilly And Company | Synthesis of ketones with calcium hypochlorite |
| US4689415A (en) * | 1984-04-18 | 1987-08-25 | Eli Lilly And Company | Trans octahydroquinoline intermediate |
| US4537893A (en) * | 1984-04-27 | 1985-08-27 | Eli Lilly And Company | Octahydrothiazolo[4,5-g]quinolines and use as prolactin secretion inhibitors |
| IL75991A0 (en) * | 1984-08-02 | 1985-12-31 | Lilly Co Eli | Octahydro-oxazolo(4,5-g)quinolines |
| US4600777A (en) * | 1984-08-02 | 1986-07-15 | Eli Lilly And Company | Method of preparing 1-alkyl-7-oxodecahydroquinolines, and cis(±) and tran(±)isomers so prepared |
| US4537965A (en) * | 1984-08-03 | 1985-08-27 | Eli Lilly And Company | Method of preparing 4aR,8aR-5-permissibly substituted-6-oxo-octahydro-1H(and 2H)-pyrazolo[3,4-g]quinolines, useful as intermediates |
| US4537964A (en) * | 1984-08-03 | 1985-08-27 | Eli Lilly And Company | Method of preparing permissibly-substituted 1H(and 2H)pyrazolo[3,4-g]quinolines; pyrimido[4,5,g]quinolines; thiazolo[4,5,g]quinolines and intermediates therefore |
| HUT40656A (en) * | 1984-08-03 | 1987-01-28 | Lilly Co Eli | Process for producing tricyclic quinoline derivatives |
| US4552956A (en) * | 1984-08-15 | 1985-11-12 | Eli Lilly And Company | Partially hydrogenated pyrazolo, pyrimido and thiazolo[1,4]benzoxazines |
| US4587336A (en) * | 1984-08-15 | 1986-05-06 | Eli Lilly And Company | Partially hydrogenated intermediate pyrazolo, pyrimido and thiazolo[1,4]benzoxazines |
| FR2578254B1 (fr) * | 1985-03-01 | 1987-03-06 | Roussel Uclaf | Nouveaux derives de la pyrazolobenzoxazine, leurs sels, procede de preparation, application a titre de medicaments, compositions les renfermant, et des intermediaires |
| US4595754A (en) * | 1985-03-04 | 1986-06-17 | Eli Lilly And Company | Process for preparing cis N-alkylperhydroquinolines |
| US4927828A (en) * | 1985-03-08 | 1990-05-22 | The Trustees Of Princeton University | Diastereoisomeric tetrahydropyrido-(2,3,d) pyrimidine derivatives |
| US4622398A (en) * | 1985-06-24 | 1986-11-11 | Eli Lilly And Company | Dialkylaminotetrahydroquinazoline |
| US5134143A (en) * | 1986-06-16 | 1992-07-28 | Eli Lilly And Company | BCD tricyclic ergoline part-structure analogues |
| US4826986A (en) * | 1986-06-16 | 1989-05-02 | Eli Lilly And Company | 6-Oxo-trans-octa- and decahydroquinolines |
| US4977160A (en) * | 1986-06-16 | 1990-12-11 | Eli Lilly And Company | BCD tricyclic ergoline part-structure analogues |
| US4762843A (en) * | 1986-09-15 | 1988-08-09 | Warner-Lambert Company | Hetero [f] fused carbocyclic pyridines as dopaminergic agents |
| US5057515A (en) * | 1989-07-24 | 1991-10-15 | Eli Lilly And Company | Method for agonizing a dopamine receptor |
| US4939259A (en) * | 1989-07-24 | 1990-07-03 | Eli Lilly And Company | 2-oxo-pyrido[2,3-g]quinoline derivatives |
| US4977149A (en) * | 1989-07-24 | 1990-12-11 | Eli Lilly And Company | Pyridoquinoline dopamine agonists, compositions and use |
| US5006525A (en) * | 1989-07-24 | 1991-04-09 | Eli Lilly And Company | Dopamine agonists method |
| DE69109125T2 (de) * | 1990-09-28 | 1995-09-28 | Pfizer | Ringverknüpfte analoge von stickstoffenthaltenden nichtaromatischen heterocyclen. |
| US5416090A (en) * | 1991-01-31 | 1995-05-16 | Eli Lilly And Company | Method of treating inflammation |
| US20030212085A1 (en) * | 2001-04-17 | 2003-11-13 | Mccall Robert B. | Treatment of fibromyalgia and chronic fatigue syndrome |
| MY148644A (en) * | 2005-07-18 | 2013-05-15 | Orion Corp | New pharmaceutical compounds |
| UY38696A (es) | 2019-05-14 | 2020-11-30 | Vertex Pharma | Moduladores de alfa-1 antitripsina |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3084165A (en) * | 1959-05-21 | 1963-04-02 | Bayer Ag | Quinone derivatives and processes for producing the same |
| US3600393A (en) * | 1969-03-03 | 1971-08-17 | Aldrich Chem Co Inc | Dialkylamino alkylamino pyrazolo (3,4b) quinolines |
| US3859291A (en) * | 1973-10-01 | 1975-01-07 | Morton Norwich Products Inc | 9-(p-anisidino)-7-methyl-(1h)-pyrazolo(3,4-f)quinoline |
| US4028381A (en) * | 1975-05-05 | 1977-06-07 | Ciba-Geigy Corporation | Pyrazolobenzazepines |
-
1979
- 1979-04-19 US US06/031,641 patent/US4198415A/en not_active Expired - Lifetime
- 1979-06-26 DK DK268879A patent/DK268879A/da not_active Application Discontinuation
- 1979-06-26 NZ NZ201279A patent/NZ201279A/en unknown
- 1979-06-26 NZ NZ190835A patent/NZ190835A/en unknown
- 1979-06-26 IL IL57668A patent/IL57668A/xx unknown
- 1979-06-26 CA CA000330552A patent/CA1136140A/en not_active Expired
- 1979-06-26 PT PT69829A patent/PT69829A/pt unknown
- 1979-06-27 RO RO79104044A patent/RO82159A/ro unknown
- 1979-06-27 LU LU81439A patent/LU81439A1/xx unknown
- 1979-06-27 FR FR7916571A patent/FR2446832A1/fr active Granted
- 1979-06-27 AU AU48445/79A patent/AU528076B2/en not_active Ceased
- 1979-06-27 PH PH22704A patent/PH14909A/en unknown
- 1979-06-27 RO RO7997973A patent/RO77563A/ro unknown
- 1979-06-28 CH CH606079A patent/CH644377A5/fr not_active IP Right Cessation
- 1979-06-28 GR GR59466A patent/GR72516B/el unknown
- 1979-06-28 GB GB8203158A patent/GB2092581A/en not_active Withdrawn
- 1979-06-28 GB GB8203156A patent/GB2092579A/en not_active Withdrawn
- 1979-06-28 DE DE8181110640T patent/DE2966945D1/de not_active Expired
- 1979-06-28 GB GB7922530A patent/GB2040915B/en not_active Expired
- 1979-06-28 AT AT0452479A patent/AT371819B/de not_active IP Right Cessation
- 1979-06-28 FI FI792046A patent/FI65247C/fi not_active IP Right Cessation
- 1979-06-28 GB GB8203157A patent/GB2092580B/en not_active Expired
- 1979-06-28 EP EP79301250A patent/EP0013787B1/en not_active Expired
- 1979-06-28 DE DE7979301250T patent/DE2966951D1/de not_active Expired
- 1979-06-28 EP EP81110640A patent/EP0050881B1/en not_active Expired
- 1979-06-29 DD DD79218313A patent/DD148340A5/de unknown
- 1979-06-29 DD DD79218310A patent/DD148517A5/de unknown
- 1979-06-29 PL PL1979225533A patent/PL119785B1/pl unknown
- 1979-06-29 ES ES482091A patent/ES482091A1/es not_active Expired
- 1979-06-29 ZA ZA793243A patent/ZA793243B/xx unknown
- 1979-06-29 DD DD79213992A patent/DD144670A5/de unknown
- 1979-06-29 PL PL1979225531A patent/PL119715B1/pl unknown
- 1979-06-29 ES ES482087A patent/ES482087A1/es not_active Expired
- 1979-06-29 DD DD79218311A patent/DD148518A5/de unknown
- 1979-06-29 DD DD79218312A patent/DD148339A5/de unknown
- 1979-06-29 PL PL1979216719A patent/PL122153B1/pl unknown
- 1979-06-29 PL PL1979225532A patent/PL120037B1/pl unknown
- 1979-06-29 ES ES482090A patent/ES482090A1/es not_active Expired
- 1979-06-29 ES ES482089A patent/ES482089A1/es not_active Expired
- 1979-06-30 EG EG393/79A patent/EG14696A/xx active
- 1979-08-08 IE IE1209/79A patent/IE48394B1/en unknown
- 1979-11-06 FR FR7927310A patent/FR2446822A1/fr active Granted
- 1979-11-06 FR FR7927309A patent/FR2446821A1/fr not_active Withdrawn
- 1979-11-06 FR FR7927311A patent/FR2446820A1/fr active Pending
- 1979-11-06 FR FR7927308A patent/FR2446834A1/fr active Granted
-
1980
- 1980-03-12 PH PH23756A patent/PH14908A/en unknown
- 1980-03-12 PH PH23757A patent/PH14991A/en unknown
-
1983
- 1983-06-20 CH CH336883A patent/CH644365A5/fr not_active IP Right Cessation
- 1983-06-20 CH CH336783A patent/CH644607A5/fr not_active IP Right Cessation
-
1985
- 1985-12-30 MY MY683/85A patent/MY8500683A/xx unknown
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| US4322430A (en) | Amino-substituted 4,5,6,7-tetrahydro-1H (or 2H)-indazoles | |
| JPS6272686A (ja) | キノリン誘導体 |
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