NO329668B1 - Kinolin- og isokinolinderivater, farmasoytiske preparater som inneholder minst en slik forbindelse, fremgangsmate for frmstilling av forbindelsene og anvendelse derav for fremstilling av farmasoytiske midler - Google Patents
Kinolin- og isokinolinderivater, farmasoytiske preparater som inneholder minst en slik forbindelse, fremgangsmate for frmstilling av forbindelsene og anvendelse derav for fremstilling av farmasoytiske midler Download PDFInfo
- Publication number
- NO329668B1 NO329668B1 NO20044731A NO20044731A NO329668B1 NO 329668 B1 NO329668 B1 NO 329668B1 NO 20044731 A NO20044731 A NO 20044731A NO 20044731 A NO20044731 A NO 20044731A NO 329668 B1 NO329668 B1 NO 329668B1
- Authority
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- Norway
- Prior art keywords
- group
- methyl
- mmol
- alkyl
- ethyl acetate
- Prior art date
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- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 title claims abstract description 14
- 125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 title claims abstract description 9
- 150000001875 compounds Chemical class 0.000 title claims description 106
- 239000008177 pharmaceutical agent Substances 0.000 title claims description 6
- 238000000034 method Methods 0.000 title abstract description 41
- 230000008569 process Effects 0.000 title abstract description 31
- 238000002360 preparation method Methods 0.000 title abstract description 12
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 239000000203 mixture Substances 0.000 claims description 81
- -1 alkyl metal compound Chemical class 0.000 claims description 60
- 229910052739 hydrogen Inorganic materials 0.000 claims description 28
- 239000001257 hydrogen Substances 0.000 claims description 27
- 238000006243 chemical reaction Methods 0.000 claims description 23
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
- 150000003254 radicals Chemical group 0.000 claims description 19
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 238000011282 treatment Methods 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical class C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 9
- 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 description 9
- 125000003118 aryl group Chemical group 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 150000002537 isoquinolines Chemical class 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 150000004716 alpha keto acids Chemical class 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 150000001721 carbon Chemical group 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 150000002148 esters Chemical class 0.000 claims description 7
- 150000002431 hydrogen Chemical class 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
- 239000003054 catalyst Substances 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 5
- 230000002829 reductive effect Effects 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 125000006833 (C1-C5) alkylene group Chemical group 0.000 claims description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical group O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- 150000005840 aryl radicals Chemical class 0.000 claims description 3
- 238000006555 catalytic reaction Methods 0.000 claims description 3
- 230000008878 coupling Effects 0.000 claims description 3
- 238000010168 coupling process Methods 0.000 claims description 3
- 238000005859 coupling reaction Methods 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 150000004799 α-ketoamides Chemical class 0.000 claims description 3
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 claims description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 2
- 238000005815 base catalysis Methods 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 claims description 2
- 208000027866 inflammatory disease Diseases 0.000 claims description 2
- 239000012038 nucleophile Substances 0.000 claims description 2
- 238000006268 reductive amination reaction Methods 0.000 claims description 2
- 230000007704 transition Effects 0.000 claims description 2
- 229910052723 transition metal Inorganic materials 0.000 claims description 2
- 150000003624 transition metals Chemical class 0.000 claims description 2
- 150000003248 quinolines Chemical class 0.000 claims 6
- 238000007796 conventional method Methods 0.000 claims 2
- 150000003377 silicon compounds Chemical class 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims 1
- 230000003213 activating effect Effects 0.000 claims 1
- 230000002757 inflammatory effect Effects 0.000 abstract description 4
- 239000003112 inhibitor Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 369
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 140
- 239000000243 solution Substances 0.000 description 133
- 239000000741 silica gel Substances 0.000 description 127
- 229910002027 silica gel Inorganic materials 0.000 description 127
- 239000000047 product Substances 0.000 description 122
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 121
- 238000005160 1H NMR spectroscopy Methods 0.000 description 115
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 97
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 94
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 90
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 87
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 84
- 238000004587 chromatography analysis Methods 0.000 description 80
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 76
- 238000001704 evaporation Methods 0.000 description 75
- 230000008020 evaporation Effects 0.000 description 73
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 72
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 64
- JYVLIDXNZAXMDK-UHFFFAOYSA-N pentan-2-ol Chemical compound CCCC(C)O JYVLIDXNZAXMDK-UHFFFAOYSA-N 0.000 description 64
- 239000002904 solvent Substances 0.000 description 61
- 239000011541 reaction mixture Substances 0.000 description 60
- 229910052938 sodium sulfate Inorganic materials 0.000 description 59
- 235000011152 sodium sulphate Nutrition 0.000 description 59
- 239000012074 organic phase Substances 0.000 description 57
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 48
- 238000000746 purification Methods 0.000 description 40
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 37
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 34
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
- 229960000583 acetic acid Drugs 0.000 description 27
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 26
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- 239000000463 material Substances 0.000 description 24
- 239000003921 oil Substances 0.000 description 24
- 235000019198 oils Nutrition 0.000 description 24
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 23
- 239000012279 sodium borohydride Substances 0.000 description 23
- 229910000033 sodium borohydride Inorganic materials 0.000 description 23
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 22
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 239000012267 brine Substances 0.000 description 19
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 19
- 230000004054 inflammatory process Effects 0.000 description 18
- 239000007787 solid Substances 0.000 description 18
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
- 208000010668 atopic eczema Diseases 0.000 description 17
- 239000000284 extract Substances 0.000 description 17
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 16
- 230000000172 allergic effect Effects 0.000 description 16
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 16
- 238000001816 cooling Methods 0.000 description 15
- 239000012071 phase Substances 0.000 description 15
- 230000002062 proliferating effect Effects 0.000 description 15
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 14
- 238000010626 work up procedure Methods 0.000 description 14
- IDWZSGZOZKRJQF-UHFFFAOYSA-N 4-(1,3-benzodioxol-4-yl)-2-hydroxy-4-methyl-n-quinolin-5-yl-2-(trifluoromethyl)pentanamide Chemical compound C=1C=CC2=NC=CC=C2C=1NC(=O)C(O)(C(F)(F)F)CC(C)(C)C1=CC=CC2=C1OCO2 IDWZSGZOZKRJQF-UHFFFAOYSA-N 0.000 description 13
- 201000010099 disease Diseases 0.000 description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 13
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 12
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 12
- WRFLLCIDQDAHGU-UHFFFAOYSA-N 4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentanal Chemical compound COC1=CC=C(F)C=C1C(C)(C)CC(O)(C=O)C(F)(F)F WRFLLCIDQDAHGU-UHFFFAOYSA-N 0.000 description 11
- 239000007832 Na2SO4 Substances 0.000 description 11
- 239000008346 aqueous phase Substances 0.000 description 11
- 238000004440 column chromatography Methods 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- 239000012298 atmosphere Substances 0.000 description 10
- MSCVLAFLUUPHBK-UHFFFAOYSA-N methyl 5-aminoquinoline-2-carboxylate Chemical compound NC1=CC=CC2=NC(C(=O)OC)=CC=C21 MSCVLAFLUUPHBK-UHFFFAOYSA-N 0.000 description 10
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N pentanal Chemical compound CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- ZAPDYOPHULUPJK-UHFFFAOYSA-N 1,1,1-trifluorohexan-3-ol Chemical compound CCCC(O)CC(F)(F)F ZAPDYOPHULUPJK-UHFFFAOYSA-N 0.000 description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
- 102000003676 Glucocorticoid Receptors Human genes 0.000 description 8
- 108090000079 Glucocorticoid Receptors Proteins 0.000 description 8
- 150000002009 diols Chemical class 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 8
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 8
- VNWUDLTYIICXJQ-UHFFFAOYSA-N 4-(1,3-benzodioxol-4-yl)-4-methyl-2-oxo-n-quinolin-5-ylpentanamide Chemical compound C=1C=CC2=NC=CC=C2C=1NC(=O)C(=O)CC(C)(C)C1=CC=CC2=C1OCO2 VNWUDLTYIICXJQ-UHFFFAOYSA-N 0.000 description 7
- 239000012230 colorless oil Substances 0.000 description 7
- 239000012043 crude product Substances 0.000 description 7
- USLKCMBGQFYUFI-UHFFFAOYSA-N dichloromethane;tribromoborane Chemical compound ClCCl.BrB(Br)Br USLKCMBGQFYUFI-UHFFFAOYSA-N 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000003862 glucocorticoid Substances 0.000 description 7
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 7
- XMIAFAKRAAMSGX-UHFFFAOYSA-N quinolin-5-amine Chemical compound C1=CC=C2C(N)=CC=CC2=N1 XMIAFAKRAAMSGX-UHFFFAOYSA-N 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 238000005406 washing Methods 0.000 description 7
- UNSLQFMTPYHZDA-UHFFFAOYSA-N 2-methylquinolin-5-amine Chemical compound NC1=CC=CC2=NC(C)=CC=C21 UNSLQFMTPYHZDA-UHFFFAOYSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 6
- 229910021529 ammonia Inorganic materials 0.000 description 6
- 239000005457 ice water Substances 0.000 description 6
- 239000012280 lithium aluminium hydride Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 239000010936 titanium Substances 0.000 description 6
- 229910052719 titanium Inorganic materials 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 5
- 102000016540 Tyrosine aminotransferases Human genes 0.000 description 5
- 108010042606 Tyrosine transaminase Proteins 0.000 description 5
- 230000003110 anti-inflammatory effect Effects 0.000 description 5
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
- 229910000024 caesium carbonate Inorganic materials 0.000 description 5
- 239000002274 desiccant Substances 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 239000012362 glacial acetic acid Substances 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 5
- 229940037128 systemic glucocorticoids Drugs 0.000 description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
- IICVTJMDHNPPOP-UHFFFAOYSA-N 2-chloro-5-nitroquinoline Chemical compound ClC1=CC=C2C([N+](=O)[O-])=CC=CC2=N1 IICVTJMDHNPPOP-UHFFFAOYSA-N 0.000 description 4
- JIMKZMITINERBL-UHFFFAOYSA-N 4-(4-chlorophenyl)-4-methyl-2-(trifluoromethyl)pentane-1,2-diol Chemical compound OCC(O)(C(F)(F)F)CC(C)(C)C1=CC=C(Cl)C=C1 JIMKZMITINERBL-UHFFFAOYSA-N 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
- LCGISIDBXHGCDW-VKHMYHEASA-N L-glutamine amide Chemical compound NC(=O)[C@@H](N)CCC(N)=O LCGISIDBXHGCDW-VKHMYHEASA-N 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 4
- 230000001154 acute effect Effects 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 4
- UZBQIPPOMKBLAS-UHFFFAOYSA-N diethylazanide Chemical compound CC[N-]CC UZBQIPPOMKBLAS-UHFFFAOYSA-N 0.000 description 4
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- CILJSZLWPHTUIP-UHFFFAOYSA-N methyl quinoline-2-carboxylate Chemical compound C1=CC=CC2=NC(C(=O)OC)=CC=C21 CILJSZLWPHTUIP-UHFFFAOYSA-N 0.000 description 4
- 239000002674 ointment Substances 0.000 description 4
- AEABQBMUYZBBCW-UHFFFAOYSA-N pentanamide Chemical compound CC[CH]CC(N)=O AEABQBMUYZBBCW-UHFFFAOYSA-N 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 239000004323 potassium nitrate Substances 0.000 description 4
- 235000010333 potassium nitrate Nutrition 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
- MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 description 4
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Landscapes
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10215316A DE10215316C1 (de) | 2002-04-02 | 2002-04-02 | Chinolin- und Isochinolin-Derivate, ein pharmazeutisches Mittel und ihre Verwendung als Entzündungshemmer |
PCT/EP2003/003298 WO2003082827A1 (de) | 2002-04-02 | 2003-03-29 | Chinolin- und isochinolin-derivate, ein verfahren zu ihrer herstellung und ihre verwendung als entzündungshemmer |
Publications (2)
Publication Number | Publication Date |
---|---|
NO20044731L NO20044731L (no) | 2004-12-30 |
NO329668B1 true NO329668B1 (no) | 2010-11-29 |
Family
ID=28458623
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20044731A NO329668B1 (no) | 2002-04-02 | 2004-11-01 | Kinolin- og isokinolinderivater, farmasoytiske preparater som inneholder minst en slik forbindelse, fremgangsmate for frmstilling av forbindelsene og anvendelse derav for fremstilling av farmasoytiske midler |
Country Status (33)
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US (1) | US7329753B2 (sl) |
EP (1) | EP1492771B1 (sl) |
JP (1) | JP4593929B2 (sl) |
KR (1) | KR100967277B1 (sl) |
CN (1) | CN1659144B (sl) |
AR (1) | AR039222A1 (sl) |
AT (1) | ATE355277T1 (sl) |
AU (1) | AU2003215678B2 (sl) |
BR (1) | BR0308967A (sl) |
CA (1) | CA2481012C (sl) |
CY (1) | CY1106598T1 (sl) |
DE (2) | DE10215316C1 (sl) |
DK (1) | DK1492771T3 (sl) |
EA (1) | EA008540B1 (sl) |
EC (1) | ECSP045399A (sl) |
ES (1) | ES2282649T3 (sl) |
HK (1) | HK1081193A1 (sl) |
HR (1) | HRP20041005B1 (sl) |
IL (1) | IL164292A (sl) |
ME (2) | ME00159B (sl) |
MX (1) | MXPA04009684A (sl) |
NO (1) | NO329668B1 (sl) |
NZ (1) | NZ535872A (sl) |
PE (1) | PE20040081A1 (sl) |
PL (1) | PL212322B1 (sl) |
PT (1) | PT1492771E (sl) |
RS (1) | RS50931B (sl) |
SI (1) | SI1492771T1 (sl) |
TW (1) | TWI272267B (sl) |
UA (1) | UA78304C2 (sl) |
UY (1) | UY27748A1 (sl) |
WO (1) | WO2003082827A1 (sl) |
ZA (1) | ZA200408827B (sl) |
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GB8617653D0 (en) * | 1986-07-18 | 1986-08-28 | Ici Plc | Amide derivatives |
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