JPH09124606A - 置換キノリン−２−カルボキサミド、それらの製造ならびに薬剤および中間体としてのそれらの使用 - Google Patents
置換キノリン−２−カルボキサミド、それらの製造ならびに薬剤および中間体としてのそれらの使用Info
- Publication number
- JPH09124606A JPH09124606A JP8276901A JP27690196A JPH09124606A JP H09124606 A JPH09124606 A JP H09124606A JP 8276901 A JP8276901 A JP 8276901A JP 27690196 A JP27690196 A JP 27690196A JP H09124606 A JPH09124606 A JP H09124606A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- alkoxy
- carbamoyl
- cycloalkyl
- group
- 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.)
- Pending
Links
- 239000003814 drug Substances 0.000 title claims abstract description 14
- 238000004519 manufacturing process Methods 0.000 title claims description 9
- ZEXKKIXCRDTKBF-UHFFFAOYSA-N quinoline-2-carboxamide Chemical class C1=CC=CC2=NC(C(=O)N)=CC=C21 ZEXKKIXCRDTKBF-UHFFFAOYSA-N 0.000 title abstract description 3
- 229940079593 drug Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 160
- -1 amide ester Chemical class 0.000 claims abstract description 139
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 25
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 23
- 150000002367 halogens Chemical class 0.000 claims abstract description 23
- 102000004079 Prolyl Hydroxylases Human genes 0.000 claims abstract description 20
- 108010043005 Prolyl Hydroxylases Proteins 0.000 claims abstract description 20
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 19
- 239000003112 inhibitor Substances 0.000 claims abstract description 18
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 11
- LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 claims abstract description 10
- 206010016654 Fibrosis Diseases 0.000 claims abstract description 9
- 230000004761 fibrosis Effects 0.000 claims abstract description 9
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims abstract description 9
- 230000036570 collagen biosynthesis Effects 0.000 claims abstract description 7
- 238000007098 aminolysis reaction Methods 0.000 claims abstract description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 96
- 239000001257 hydrogen Substances 0.000 claims description 96
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 92
- 125000001424 substituent group Chemical group 0.000 claims description 87
- 239000000460 chlorine Substances 0.000 claims description 84
- 229910052801 chlorine Inorganic materials 0.000 claims description 73
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 71
- 229910052731 fluorine Inorganic materials 0.000 claims description 71
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 71
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 68
- 239000011737 fluorine Substances 0.000 claims description 68
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 63
- 229910052794 bromium Inorganic materials 0.000 claims description 61
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 59
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 59
- 150000002431 hydrogen Chemical class 0.000 claims description 56
- 229910052757 nitrogen Inorganic materials 0.000 claims description 47
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 40
- 150000003839 salts Chemical class 0.000 claims description 40
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 30
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 29
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 27
- 125000005146 naphthylsulfonyl group Chemical group C1(=CC=CC2=CC=CC=C12)S(=O)(=O)* 0.000 claims description 25
- 125000001624 naphthyl group Chemical group 0.000 claims description 24
- 229910052717 sulfur Inorganic materials 0.000 claims description 22
- 229910052760 oxygen Inorganic materials 0.000 claims description 19
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 18
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 15
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 15
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 14
- 125000004642 (C1-C12) alkoxy group Chemical group 0.000 claims description 13
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 13
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 12
- 125000006625 (C3-C8) cycloalkyloxy group Chemical group 0.000 claims description 11
- 125000006239 protecting group Chemical group 0.000 claims description 11
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 10
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 10
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 150000002825 nitriles Chemical class 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 229940002612 prodrug Drugs 0.000 claims description 7
- 239000000651 prodrug Substances 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- 239000013067 intermediate product Substances 0.000 claims description 6
- 125000006702 (C1-C18) alkyl group Chemical group 0.000 claims description 5
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 5
- 150000008575 L-amino acids Chemical class 0.000 claims description 5
- 235000008206 alpha-amino acids Nutrition 0.000 claims description 5
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 5
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000001072 heteroaryl group Chemical group 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 3
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 claims description 3
- 125000003435 aroyl group Chemical group 0.000 claims description 3
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 2
- 150000007650 D alpha amino acids Chemical class 0.000 claims description 2
- 125000005277 alkyl imino group Chemical group 0.000 claims description 2
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 239000000543 intermediate Substances 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- 230000001590 oxidative effect Effects 0.000 claims description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 2
- LQVXSNNAFNGRAH-QHCPKHFHSA-N BMS-754807 Chemical compound C([C@@]1(C)C(=O)NC=2C=NC(F)=CC=2)CCN1C(=NN1C=CC=C11)N=C1NC(=NN1)C=C1C1CC1 LQVXSNNAFNGRAH-QHCPKHFHSA-N 0.000 claims 1
- 229910003827 NRaRb Inorganic materials 0.000 claims 1
- 125000003275 alpha amino acid group Chemical group 0.000 claims 1
- 125000005140 aralkylsulfonyl group Chemical group 0.000 claims 1
- 125000000946 retinyl group Chemical group [H]C([*])([H])/C([H])=C(C([H])([H])[H])/C([H])=C([H])/C([H])=C(C([H])([H])[H])/C([H])=C([H])/C1=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])C1(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 125000003396 thiol group Chemical class [H]S* 0.000 claims 1
- JMVWZMFXDTXDFI-UHFFFAOYSA-N 2-[(3-hydroxyquinoline-2-carbonyl)amino]acetic acid Chemical compound C1=CC=C2C=C(O)C(C(=O)NCC(=O)O)=NC2=C1 JMVWZMFXDTXDFI-UHFFFAOYSA-N 0.000 abstract description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 abstract 1
- 229940124597 therapeutic agent Drugs 0.000 abstract 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 150
- 239000000047 product Substances 0.000 description 88
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 81
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 80
- 239000004471 Glycine Substances 0.000 description 77
- 229960002449 glycine Drugs 0.000 description 77
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 69
- 238000002844 melting Methods 0.000 description 65
- 230000008018 melting Effects 0.000 description 65
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 39
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
- 239000000203 mixture Substances 0.000 description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 31
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- 239000003208 petroleum Substances 0.000 description 28
- 239000000243 solution Substances 0.000 description 28
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 23
- 239000012043 crude product Substances 0.000 description 23
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- 239000000741 silica gel Substances 0.000 description 21
- 229910002027 silica gel Inorganic materials 0.000 description 21
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 16
- 210000004185 liver Anatomy 0.000 description 15
- 238000004587 chromatography analysis Methods 0.000 description 14
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 14
- 238000001816 cooling Methods 0.000 description 13
- JXYACYYPACQCDM-UHFFFAOYSA-N Benzyl glycinate Chemical compound NCC(=O)OCC1=CC=CC=C1 JXYACYYPACQCDM-UHFFFAOYSA-N 0.000 description 12
- 108010035532 Collagen Proteins 0.000 description 12
- 102000008186 Collagen Human genes 0.000 description 12
- 229920001436 collagen Polymers 0.000 description 12
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 12
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
- HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 11
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 10
- 241000272525 Anas platyrhynchos Species 0.000 description 10
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 10
- 238000000034 method Methods 0.000 description 10
- GBCAVSYHPPARHX-UHFFFAOYSA-M n'-cyclohexyl-n-[2-(4-methylmorpholin-4-ium-4-yl)ethyl]methanediimine;4-methylbenzenesulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1.C1CCCCC1N=C=NCC[N+]1(C)CCOCC1 GBCAVSYHPPARHX-UHFFFAOYSA-M 0.000 description 10
- 229910000027 potassium carbonate Inorganic materials 0.000 description 10
- 241000700159 Rattus Species 0.000 description 9
- WJKJXKRHMUXQSL-UHFFFAOYSA-N benzyl glycinate 4-methylbenzenesulfonate salt Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1.NCC(=O)OCC1=CC=CC=C1 WJKJXKRHMUXQSL-UHFFFAOYSA-N 0.000 description 9
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 9
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 9
- 229960002429 proline Drugs 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 238000007254 oxidation reaction Methods 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 238000000354 decomposition reaction Methods 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 230000003647 oxidation Effects 0.000 description 6
- JHFOWEGCZWLHNW-UHFFFAOYSA-N 4-fluoro-2-methyl-1-nitrobenzene Chemical compound CC1=CC(F)=CC=C1[N+]([O-])=O JHFOWEGCZWLHNW-UHFFFAOYSA-N 0.000 description 5
- 102000004266 Collagen Type IV Human genes 0.000 description 5
- 108010042086 Collagen Type IV Proteins 0.000 description 5
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 5
- 150000001204 N-oxides Chemical class 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000005911 haloform reaction Methods 0.000 description 5
- 238000005984 hydrogenation reaction Methods 0.000 description 5
- WVDDGKGOMKODPV-UHFFFAOYSA-N hydroxymethyl benzene Natural products OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 5
- 229960002591 hydroxyproline Drugs 0.000 description 5
- HZOJBKMCYYWXAE-UHFFFAOYSA-N magnesium pentane-2,4-dione Chemical compound [Mg+2].CC(=O)CC([CH2-])=O.CC(=O)CC([CH2-])=O HZOJBKMCYYWXAE-UHFFFAOYSA-N 0.000 description 5
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- SLAMLWHELXOEJZ-UHFFFAOYSA-N 2-nitrobenzoic acid Chemical class OC(=O)C1=CC=CC=C1[N+]([O-])=O SLAMLWHELXOEJZ-UHFFFAOYSA-N 0.000 description 4
- 239000005711 Benzoic acid Substances 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 150000001408 amides Chemical group 0.000 description 4
- 235000010233 benzoic acid Nutrition 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 239000012286 potassium permanganate Substances 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 description 3
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229940024606 amino acid Drugs 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- ONDMKQWGMAVUNZ-UHFFFAOYSA-N butyl 2-aminoacetate Chemical compound CCCCOC(=O)CN ONDMKQWGMAVUNZ-UHFFFAOYSA-N 0.000 description 3
- NFCPBBXWCPNVDP-UHFFFAOYSA-N butyl 2-aminoacetate;4-methylbenzenesulfonic acid Chemical compound CCCCOC(=O)CN.CC1=CC=C(S(O)(=O)=O)C=C1 NFCPBBXWCPNVDP-UHFFFAOYSA-N 0.000 description 3
- 150000007942 carboxylates Chemical group 0.000 description 3
- 238000005187 foaming Methods 0.000 description 3
- 210000003494 hepatocyte Anatomy 0.000 description 3
- 238000005805 hydroxylation reaction Methods 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 150000003248 quinolines Chemical class 0.000 description 3
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
- 238000010626 work up procedure Methods 0.000 description 3
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 description 2
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 description 2
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 description 2
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 description 2
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 description 2
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- 210000004899 c-terminal region Anatomy 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
- 238000003501 co-culture Methods 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
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- 238000005859 coupling reaction Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
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- 229940088598 enzyme Drugs 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 239000010696 ester oil Substances 0.000 description 1
- NTNZTEQNFHNYBC-UHFFFAOYSA-N ethyl 2-aminoacetate Chemical compound CCOC(=O)CN NTNZTEQNFHNYBC-UHFFFAOYSA-N 0.000 description 1
- YEMPERUHXORKOO-UHFFFAOYSA-N ethyl 3-hydroxyquinoline-2-carboxylate Chemical compound C1=CC=C2C=C(O)C(C(=O)OCC)=NC2=C1 YEMPERUHXORKOO-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 102000005396 glutamine synthetase Human genes 0.000 description 1
- 108020002326 glutamine synthetase Proteins 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
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- 230000006698 induction Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical class II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- ZDIVCPODDCJMDM-UHFFFAOYSA-N methyl 3-methoxyquinoline-2-carboxylate Chemical compound C1=CC=C2C=C(OC)C(C(=O)OC)=NC2=C1 ZDIVCPODDCJMDM-UHFFFAOYSA-N 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- VMESOKCXSYNAKD-UHFFFAOYSA-N n,n-dimethylhydroxylamine Chemical compound CN(C)O VMESOKCXSYNAKD-UHFFFAOYSA-N 0.000 description 1
- 150000005440 nitrobenzoic acid derivatives Chemical class 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- VLZLOWPYUQHHCG-UHFFFAOYSA-N nitromethylbenzene Chemical compound [O-][N+](=O)CC1=CC=CC=C1 VLZLOWPYUQHHCG-UHFFFAOYSA-N 0.000 description 1
- 238000007339 nucleophilic aromatic substitution reaction Methods 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
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- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- SATVIFGJTRRDQU-UHFFFAOYSA-N potassium hypochlorite Chemical compound [K+].Cl[O-] SATVIFGJTRRDQU-UHFFFAOYSA-N 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
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- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- LOAUVZALPPNFOQ-UHFFFAOYSA-M quinaldate Chemical compound C1=CC=CC2=NC(C(=O)[O-])=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-M 0.000 description 1
- 125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
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- 238000007363 ring formation reaction Methods 0.000 description 1
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- 239000002002 slurry Substances 0.000 description 1
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- 229910052708 sodium Inorganic materials 0.000 description 1
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- 210000004500 stellate cell Anatomy 0.000 description 1
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- 238000010189 synthetic method Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
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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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Dermatology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Electroluminescent Light Sources (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19536263A DE19536263A1 (de) | 1995-09-28 | 1995-09-28 | Substituierte Chinolin-2-carbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel |
| DE19605170:3 | 1996-02-13 | ||
| DE19605170 | 1996-02-13 | ||
| DE19536263:2 | 1996-02-13 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH09124606A true JPH09124606A (ja) | 1997-05-13 |
| JPH09124606A5 JPH09124606A5 (enExample) | 2004-10-07 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP8276901A Pending JPH09124606A (ja) | 1995-09-28 | 1996-09-30 | 置換キノリン−２−カルボキサミド、それらの製造ならびに薬剤および中間体としてのそれらの使用 |
Country Status (20)
| Country | Link |
|---|---|
| US (2) | US5726305A (enExample) |
| EP (1) | EP0765871B1 (enExample) |
| JP (1) | JPH09124606A (enExample) |
| KR (1) | KR970061869A (enExample) |
| CN (2) | CN1120157C (enExample) |
| AT (1) | ATE263155T1 (enExample) |
| AU (1) | AU728208B2 (enExample) |
| CA (1) | CA2186717A1 (enExample) |
| CZ (1) | CZ283396A3 (enExample) |
| DE (1) | DE59610950D1 (enExample) |
| ES (1) | ES2215184T3 (enExample) |
| HU (1) | HUP9602685A3 (enExample) |
| IL (2) | IL135495A (enExample) |
| MX (1) | MX9604378A (enExample) |
| MY (1) | MY133647A (enExample) |
| NO (1) | NO308600B1 (enExample) |
| NZ (1) | NZ299455A (enExample) |
| PL (1) | PL316321A1 (enExample) |
| SG (1) | SG45503A1 (enExample) |
| SI (1) | SI9600287A (enExample) |
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| JP2005526010A (ja) * | 2001-12-06 | 2005-09-02 | ファイブローゲン、インコーポレーテッド | 低酸素誘導性因子（ＨＩＦ）−αの安定化 |
| JP2006056894A (ja) * | 1997-10-20 | 2006-03-02 | Fibrogen Inc | 置換イソキノリン−３−カルボキサミド、その製法および薬剤としてのその使用 |
| JP2006514112A (ja) * | 2002-12-06 | 2006-04-27 | ファイブローゲン、インコーポレーテッド | 糖尿病の治療 |
| JP2006527199A (ja) * | 2003-06-06 | 2006-11-30 | ファイブロジェン，インコーポレイテッド | 赤血球形成を増強するためのＨＩＦα安定剤の使用 |
| JP2009519249A (ja) * | 2005-12-09 | 2009-05-14 | アムジエン・インコーポレーテツド | プロリルヒドロキシラーゼ阻害活性を示すキノロンベースの化合物、およびこの組成物、およびこの使用 |
| JP2011148810A (ja) * | 2003-06-06 | 2011-08-04 | Fibrogen Inc | 窒素含有ヘテロアリール化合物および内因性エリトロポエチンを増加させる際のそれらの使用方法 |
| JP2015524812A (ja) * | 2012-07-27 | 2015-08-27 | バイオジェン・エムエイ・インコーポレイテッドＢｉｏｇｅｎ ＭＡ Ｉｎｃ． | Ａｔｘ調節剤 |
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| DE19650215A1 (de) * | 1996-12-04 | 1998-06-10 | Hoechst Ag | 3-Hydroxypyridin-2-carbonsäureamidester, ihre Herstellung und ihre Verwendung als Arzneimittel |
| US20020198145A1 (en) * | 1999-06-10 | 2002-12-26 | Cognetix, Inc. | MuO-conopeptides and their use as local anesthetics |
| CA2432642A1 (en) | 2000-12-21 | 2002-08-08 | Subhash P. Khanapure | Substituted aryl compounds as novel cyclooxygenase-2 selective inhibitors, compositions and methods of use |
| JP4590157B2 (ja) * | 2001-03-21 | 2010-12-01 | アイシス イノヴェイション リミテッド | アッセイ、方法および手段 |
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| US7618940B2 (en) | 2002-12-06 | 2009-11-17 | Fibrogen, Inc. | Fat regulation |
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| CN101849943A (zh) * | 2005-06-06 | 2010-10-06 | 菲布罗根公司 | 使用HIFα稳定剂的改进的贫血治疗 |
| EP1919463B9 (en) | 2005-06-15 | 2011-02-02 | Fibrogen, Inc. | Use of hif 1alfa modulators for treatment of cancer |
| AU2006286654A1 (en) | 2005-07-27 | 2007-03-08 | F. Hoffmann-La Roche Ag | 4-aryloxy quinoline derivatives as 5-HT6 modulators |
| MX2008009581A (es) | 2006-01-27 | 2009-01-07 | Fibrogen Inc | Compuestos de cianoisoquinolina que estabilizan el factor inducible hipoxia (fih). |
| US7745461B1 (en) | 2006-02-27 | 2010-06-29 | Alcon Research, Ltd. | Method of treating dry eye disorders |
| US7625927B2 (en) * | 2006-02-27 | 2009-12-01 | Alcon Research, Ltd. | Method of treating glaucoma |
| JP5247677B2 (ja) * | 2006-03-30 | 2013-07-24 | エルジー エレクトロニクス インコーポレイティド | ビデオ信号のデコーディング／エンコーディング方法及び装置 |
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| MX2009000286A (es) | 2006-06-26 | 2009-03-20 | Procter & Gamble | Inhibidores de prolil hidroxilasa y metodos de uso. |
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| NZ600674A (en) * | 2009-12-17 | 2013-05-31 | Merck Sharp & Dohme | Quinoline amide m1 receptor positive allosteric modulators |
| JP6002155B2 (ja) | 2011-02-07 | 2016-10-05 | バイオジェン・エムエイ・インコーポレイテッドＢｉｏｇｅｎ ＭＡ Ｉｎｃ． | Ｓ１ｐ調節薬 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4015255A1 (de) * | 1990-05-12 | 1991-11-14 | Hoechst Ag | Oxalyl-aminosaeurederivate, verfahren zu ihrer herstellung und ihrer verwendung als arzneimittel zur inhibierung der prolyl-hydroxylase |
| US5192773A (en) * | 1990-07-02 | 1993-03-09 | Vertex Pharmaceuticals, Inc. | Immunosuppressive compounds |
| EP0541042A1 (de) * | 1991-11-05 | 1993-05-12 | Hoechst Aktiengesellschaft | Pyridin-2,4- und 2,5-dicarbonsäureamide und deren Derivate, Verfahren zu ihrer Herstellung sowie deren Verwendung als Arzneimittel |
| TW352384B (en) * | 1992-03-24 | 1999-02-11 | Hoechst Ag | Sulfonamido- or sulfonamidocarbonylpyridine-2-carboxamides, process for their preparation and their use as pharmaceuticals |
| DE4233124A1 (de) * | 1992-10-02 | 1994-04-07 | Hoechst Ag | Acylsulfonamido- und Sulfonamidopyridin-2-carbonsäureester sowie ihre Pyridin-N-oxide, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| DK122693D0 (da) * | 1993-10-29 | 1993-10-29 | Hempels Skibsfarve Fab J C | Marin struktur |
| EP0650961B1 (de) * | 1993-11-02 | 1997-03-05 | Hoechst Aktiengesellschaft | Substituierte heterocyclische Carbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel |
| DE59401923D1 (de) * | 1993-11-02 | 1997-04-10 | Hoechst Ag | Substituierte heterocyclische Carbonsäureamidester, ihre Herstellung und ihre Verwendung als Arzneimittel |
| TW406076B (en) * | 1993-12-30 | 2000-09-21 | Hoechst Ag | Substituted heterocyclic carboxamides, their preparation and their use as pharmaceuticals |
-
1996
- 1996-06-29 IL IL13549596A patent/IL135495A/en not_active IP Right Cessation
- 1996-07-03 US US08/675,155 patent/US5726305A/en not_active Expired - Lifetime
- 1996-07-03 US US08/675,208 patent/US5719164A/en not_active Expired - Lifetime
- 1996-09-20 DE DE59610950T patent/DE59610950D1/de not_active Expired - Lifetime
- 1996-09-20 EP EP96115110A patent/EP0765871B1/de not_active Expired - Lifetime
- 1996-09-20 ES ES96115110T patent/ES2215184T3/es not_active Expired - Lifetime
- 1996-09-20 AT AT96115110T patent/ATE263155T1/de not_active IP Right Cessation
- 1996-09-25 KR KR1019960042606A patent/KR970061869A/ko not_active Ceased
- 1996-09-26 CN CN96122806A patent/CN1120157C/zh not_active Expired - Lifetime
- 1996-09-26 NZ NZ299455A patent/NZ299455A/en unknown
- 1996-09-26 AU AU65838/96A patent/AU728208B2/en not_active Ceased
- 1996-09-26 CZ CZ962833A patent/CZ283396A3/cs unknown
- 1996-09-26 IL IL11930296A patent/IL119302A0/xx unknown
- 1996-09-27 SI SI9600287A patent/SI9600287A/sl unknown
- 1996-09-27 MX MX9604378A patent/MX9604378A/es unknown
- 1996-09-27 MY MYPI96004023A patent/MY133647A/en unknown
- 1996-09-27 CA CA002186717A patent/CA2186717A1/en not_active Abandoned
- 1996-09-27 PL PL96316321A patent/PL316321A1/xx unknown
- 1996-09-27 HU HU9602685A patent/HUP9602685A3/hu unknown
- 1996-09-27 NO NO964093A patent/NO308600B1/no not_active IP Right Cessation
- 1996-09-27 SG SG1996010735A patent/SG45503A1/en unknown
- 1996-09-30 JP JP8276901A patent/JPH09124606A/ja active Pending
-
2000
- 2000-06-14 CN CN00118801A patent/CN1282737A/zh active Pending
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006056894A (ja) * | 1997-10-20 | 2006-03-02 | Fibrogen Inc | 置換イソキノリン−３−カルボキサミド、その製法および薬剤としてのその使用 |
| JP2011037862A (ja) * | 2001-12-06 | 2011-02-24 | Fibrogen Inc | 内因性エリスロポエチン（ｅｐｏ）を増加させる方法 |
| JP2006137763A (ja) * | 2001-12-06 | 2006-06-01 | Fibrogen Inc | 内因性エリスロポエチン（ｅｐｏ）を増加させる方法 |
| JP2005526010A (ja) * | 2001-12-06 | 2005-09-02 | ファイブローゲン、インコーポレーテッド | 低酸素誘導性因子（ＨＩＦ）−αの安定化 |
| JP2011046733A (ja) * | 2001-12-06 | 2011-03-10 | Fibrogen Inc | 低酸素誘導性因子（ＨＩＦ）−αの安定化 |
| JP2006514112A (ja) * | 2002-12-06 | 2006-04-27 | ファイブローゲン、インコーポレーテッド | 糖尿病の治療 |
| JP2006527199A (ja) * | 2003-06-06 | 2006-11-30 | ファイブロジェン，インコーポレイテッド | 赤血球形成を増強するためのＨＩＦα安定剤の使用 |
| JP2011057697A (ja) * | 2003-06-06 | 2011-03-24 | Fibrogen Inc | 赤血球形成を増強するためのＨＩＦα安定剤の使用 |
| JP2011148810A (ja) * | 2003-06-06 | 2011-08-04 | Fibrogen Inc | 窒素含有ヘテロアリール化合物および内因性エリトロポエチンを増加させる際のそれらの使用方法 |
| JP2011178809A (ja) * | 2003-06-06 | 2011-09-15 | Fibrogen Inc | 赤血球形成を増強するためのＨＩＦα安定剤の使用 |
| JP2009519249A (ja) * | 2005-12-09 | 2009-05-14 | アムジエン・インコーポレーテツド | プロリルヒドロキシラーゼ阻害活性を示すキノロンベースの化合物、およびこの組成物、およびこの使用 |
| JP2015524812A (ja) * | 2012-07-27 | 2015-08-27 | バイオジェン・エムエイ・インコーポレイテッドＢｉｏｇｅｎ ＭＡ Ｉｎｃ． | Ａｔｘ調節剤 |
| JP2018135379A (ja) * | 2012-07-27 | 2018-08-30 | バイオジェン・エムエイ・インコーポレイテッドＢｉｏｇｅｎ ＭＡ Ｉｎｃ． | Ａｔｘ調節剤 |
Also Published As
| Publication number | Publication date |
|---|---|
| ES2215184T3 (es) | 2004-10-01 |
| MY133647A (en) | 2007-11-30 |
| US5719164A (en) | 1998-02-17 |
| DE59610950D1 (de) | 2004-05-06 |
| NZ299455A (en) | 1997-06-24 |
| NO964093L (no) | 1997-04-01 |
| CN1154365A (zh) | 1997-07-16 |
| MX9604378A (es) | 1997-03-29 |
| IL135495A (en) | 2002-12-01 |
| EP0765871B1 (de) | 2004-03-31 |
| IL119302A0 (en) | 1996-12-05 |
| SI9600287A (en) | 1997-04-30 |
| PL316321A1 (en) | 1997-04-01 |
| SG45503A1 (en) | 1998-01-16 |
| US5726305A (en) | 1998-03-10 |
| CZ283396A3 (en) | 1997-04-16 |
| CA2186717A1 (en) | 1997-03-29 |
| CN1282737A (zh) | 2001-02-07 |
| ATE263155T1 (de) | 2004-04-15 |
| NO964093D0 (no) | 1996-09-27 |
| HUP9602685A2 (hu) | 1998-09-28 |
| CN1120157C (zh) | 2003-09-03 |
| AU728208B2 (en) | 2001-01-04 |
| EP0765871A1 (de) | 1997-04-02 |
| AU6583896A (en) | 1997-04-10 |
| HUP9602685A3 (en) | 2001-04-28 |
| NO308600B1 (no) | 2000-10-02 |
| KR970061869A (ko) | 1997-09-12 |
| HU9602685D0 (en) | 1996-11-28 |
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