CA2481012C - Quinoline and isoquinoline derivatives, a process for their production and their use as inflammation inhibitors - Google Patents
Quinoline and isoquinoline derivatives, a process for their production and their use as inflammation inhibitors Download PDFInfo
- Publication number
- CA2481012C CA2481012C CA2481012A CA2481012A CA2481012C CA 2481012 C CA2481012 C CA 2481012C CA 2481012 A CA2481012 A CA 2481012A CA 2481012 A CA2481012 A CA 2481012A CA 2481012 C CA2481012 C CA 2481012C
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- Canada
- Prior art keywords
- methyl
- group
- mmol
- trifluoromethyl
- alkyl
- 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 - Fee Related
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- 238000000034 method Methods 0.000 title claims abstract description 48
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 title claims abstract description 16
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 12
- 125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 title claims abstract description 10
- 230000008569 process Effects 0.000 title claims description 43
- 230000004054 inflammatory process Effects 0.000 title description 7
- 206010061218 Inflammation Diseases 0.000 title description 6
- 239000003112 inhibitor Substances 0.000 title description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 184
- 150000001875 compounds Chemical class 0.000 claims description 110
- -1 alkyl metal compound Chemical class 0.000 claims description 38
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 32
- 239000001257 hydrogen Substances 0.000 claims description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims description 31
- 238000006243 chemical reaction Methods 0.000 claims description 26
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 18
- 150000003254 radicals Chemical class 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 11
- 125000003118 aryl group Chemical group 0.000 claims description 10
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical class C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 10
- 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
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 150000002537 isoquinolines Chemical class 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
- 239000008177 pharmaceutical agent Substances 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
- 239000003054 catalyst Substances 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 230000002829 reductive effect Effects 0.000 claims description 5
- 238000011282 treatment Methods 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical group O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 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
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 229910052723 transition metal Inorganic materials 0.000 claims description 3
- 150000003624 transition metals 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
- 230000003213 activating effect Effects 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
- 238000007327 hydrogenolysis reaction Methods 0.000 claims description 2
- 239000012038 nucleophile Substances 0.000 claims description 2
- 238000006268 reductive amination reaction Methods 0.000 claims description 2
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims 14
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 6
- 150000003248 quinolines Chemical class 0.000 claims 6
- 150000001721 carbon Chemical group 0.000 claims 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 2
- 208000027866 inflammatory disease Diseases 0.000 claims 2
- 150000003377 silicon compounds Chemical class 0.000 claims 2
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 238000007796 conventional method Methods 0.000 claims 1
- 229940121363 anti-inflammatory agent Drugs 0.000 abstract 1
- 239000002260 anti-inflammatory agent Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 366
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 146
- 239000000243 solution Substances 0.000 description 131
- 239000000741 silica gel Substances 0.000 description 130
- 229910002027 silica gel Inorganic materials 0.000 description 130
- 238000005160 1H NMR spectroscopy Methods 0.000 description 119
- 239000000047 product Substances 0.000 description 117
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 110
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 102
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 93
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 91
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 88
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 86
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 84
- 238000004587 chromatography analysis Methods 0.000 description 84
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 84
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 73
- 238000001704 evaporation Methods 0.000 description 71
- 230000008020 evaporation Effects 0.000 description 71
- 239000002904 solvent Substances 0.000 description 62
- 101150041968 CDC13 gene Proteins 0.000 description 50
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 50
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 48
- 229910052938 sodium sulfate Inorganic materials 0.000 description 48
- 235000011152 sodium sulphate Nutrition 0.000 description 48
- 239000012074 organic phase Substances 0.000 description 42
- 238000000746 purification Methods 0.000 description 39
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 38
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 37
- 229910052740 iodine Inorganic materials 0.000 description 36
- 239000000460 chlorine Substances 0.000 description 34
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 33
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 29
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 28
- 229960000583 acetic acid Drugs 0.000 description 26
- 239000003921 oil Substances 0.000 description 24
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 23
- 239000011541 reaction mixture Substances 0.000 description 23
- 239000012279 sodium borohydride Substances 0.000 description 23
- 229910000033 sodium borohydride Inorganic materials 0.000 description 23
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 239000007787 solid Substances 0.000 description 20
- 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
- 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 18
- 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 18
- 208000010668 atopic eczema Diseases 0.000 description 18
- 230000002757 inflammatory effect Effects 0.000 description 18
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 17
- 239000000203 mixture Substances 0.000 description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- 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
- 230000000172 allergic effect Effects 0.000 description 16
- 239000008346 aqueous phase Substances 0.000 description 16
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 16
- 230000002062 proliferating effect Effects 0.000 description 15
- 229920006395 saturated elastomer Polymers 0.000 description 15
- 238000003756 stirring Methods 0.000 description 14
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 14
- 239000000284 extract Substances 0.000 description 13
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- 201000010099 disease Diseases 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 11
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 239000012298 atmosphere Substances 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 10
- 238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 10
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 9
- 229910052796 boron Inorganic materials 0.000 description 9
- 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 9
- 239000012071 phase Substances 0.000 description 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 8
- 102000003676 Glucocorticoid Receptors Human genes 0.000 description 8
- 108090000079 Glucocorticoid Receptors Proteins 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 8
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
- UNSLQFMTPYHZDA-UHFFFAOYSA-N 2-methylquinolin-5-amine Chemical compound NC1=CC=CC2=NC(C)=CC=C21 UNSLQFMTPYHZDA-UHFFFAOYSA-N 0.000 description 7
- 239000012230 colorless oil Substances 0.000 description 7
- 239000003862 glucocorticoid Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 239000005457 ice water Substances 0.000 description 6
- 239000012280 lithium aluminium hydride Substances 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 239000012321 sodium triacetoxyborohydride 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
- 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 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 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
- 239000012362 glacial acetic acid Substances 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 description 5
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- XMIAFAKRAAMSGX-UHFFFAOYSA-N quinolin-5-amine Chemical compound C1=CC=C2C(N)=CC=CC2=N1 XMIAFAKRAAMSGX-UHFFFAOYSA-N 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 229940037128 systemic glucocorticoids Drugs 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- JJPSZKIOGBRMHK-UHFFFAOYSA-N 2,6-dimethylquinoline Chemical compound N1=C(C)C=CC2=CC(C)=CC=C21 JJPSZKIOGBRMHK-UHFFFAOYSA-N 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 239000005909 Kieselgur Substances 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- UZBQIPPOMKBLAS-UHFFFAOYSA-N diethylazanide Chemical compound CC[N-]CC UZBQIPPOMKBLAS-UHFFFAOYSA-N 0.000 description 4
- 150000002009 diols Chemical class 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 210000004185 liver Anatomy 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
- 239000004323 potassium nitrate Substances 0.000 description 4
- 235000010333 potassium nitrate Nutrition 0.000 description 4
- 239000002244 precipitate Substances 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
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- PWTRJTSMRTULMY-UHFFFAOYSA-N 2-(5-bromo-2-methoxyphenyl)propan-2-ol Chemical compound COC1=CC=C(Br)C=C1C(C)(C)O PWTRJTSMRTULMY-UHFFFAOYSA-N 0.000 description 3
- YNOKAQICKKMEPH-UHFFFAOYSA-N 2-methoxyquinolin-5-amine Chemical compound NC1=CC=CC2=NC(OC)=CC=C21 YNOKAQICKKMEPH-UHFFFAOYSA-N 0.000 description 3
- IYLAEBLVXYDTHX-UHFFFAOYSA-N 4-(1,3-benzodioxol-4-yl)-4-methyl-2-oxopentanoic acid Chemical compound OC(=O)C(=O)CC(C)(C)C1=CC=CC2=C1OCO2 IYLAEBLVXYDTHX-UHFFFAOYSA-N 0.000 description 3
- VMHXBMYMTJOSSG-UHFFFAOYSA-N 4-(4-chlorophenyl)-4-methyl-2-oxopentanoic acid Chemical compound OC(=O)C(=O)CC(C)(C)C1=CC=C(Cl)C=C1 VMHXBMYMTJOSSG-UHFFFAOYSA-N 0.000 description 3
- CMZRGZILWKLDMH-UHFFFAOYSA-N 5-nitro-1-oxidoquinolin-1-ium Chemical compound C1=CC=C2C([N+](=O)[O-])=CC=CC2=[N+]1[O-] CMZRGZILWKLDMH-UHFFFAOYSA-N 0.000 description 3
- 206010002199 Anaphylactic shock Diseases 0.000 description 3
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- 206010020751 Hypersensitivity Diseases 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 208000003455 anaphylaxis Diseases 0.000 description 3
- 108010080146 androgen receptors Proteins 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 239000012876 carrier material Substances 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229940117173 croton oil Drugs 0.000 description 3
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 3
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- 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
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- 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
- C07D215/38—Nitrogen atoms
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- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
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Landscapes
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Applications Claiming Priority (3)
| 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 |
| DE10215316.7 | 2002-04-02 | ||
| 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 |
|---|---|
| CA2481012A1 CA2481012A1 (en) | 2003-10-09 |
| CA2481012C true CA2481012C (en) | 2010-01-26 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2481012A Expired - Fee Related CA2481012C (en) | 2002-04-02 | 2003-03-29 | Quinoline and isoquinoline derivatives, a process for their production and their use as inflammation inhibitors |
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| GB8617653D0 (en) * | 1986-07-18 | 1986-08-28 | Ici Plc | Amide derivatives |
| DE19723722A1 (de) * | 1997-05-30 | 1998-12-10 | Schering Ag | Nichtsteroidale Gestagene |
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| DE10038639A1 (de) * | 2000-07-28 | 2002-02-21 | Schering Ag | Nichtsteroidale Entzündungshemmer |
| US6897224B2 (en) * | 2002-04-02 | 2005-05-24 | Schering Ag | Quinoline and isoquinoline derivatives, a process for their production and their use as inflammation inhibitors |
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