KR100618922B1 - 치환된이소퀴놀린-3-카복스아미드,이의제조방법및이를포함하는약제학적조성물 - Google Patents
치환된이소퀴놀린-3-카복스아미드,이의제조방법및이를포함하는약제학적조성물 Download PDFInfo
- Publication number
- KR100618922B1 KR100618922B1 KR1019980043578A KR19980043578A KR100618922B1 KR 100618922 B1 KR100618922 B1 KR 100618922B1 KR 1019980043578 A KR1019980043578 A KR 1019980043578A KR 19980043578 A KR19980043578 A KR 19980043578A KR 100618922 B1 KR100618922 B1 KR 100618922B1
- Authority
- KR
- South Korea
- Prior art keywords
- hydrogen
- formula
- chlorine
- compound
- alkoxy
- 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 - Lifetime
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- 239000008194 pharmaceutical composition Substances 0.000 title claims 6
- KKSZSACCVDIWIE-UHFFFAOYSA-N isoquinoline-3-carboxamide Chemical class C1=CC=C2C=NC(C(=O)N)=CC2=C1 KKSZSACCVDIWIE-UHFFFAOYSA-N 0.000 title abstract description 5
- 238000002360 preparation method Methods 0.000 title description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 107
- 239000001257 hydrogen Substances 0.000 claims abstract description 107
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 94
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 78
- 239000000460 chlorine Substances 0.000 claims abstract description 78
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 78
- 150000003839 salts Chemical class 0.000 claims abstract description 38
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims abstract description 34
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 22
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000011737 fluorine Substances 0.000 claims abstract description 21
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 21
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 21
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims abstract description 18
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 14
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 13
- 150000001875 compounds Chemical class 0.000 claims description 116
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 70
- -1 (C 1 -C 8 ) -alkoxy Chemical compound 0.000 claims description 50
- 239000004471 Glycine Substances 0.000 claims description 36
- 238000000034 method Methods 0.000 claims description 21
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 17
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims description 16
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 201000010099 disease Diseases 0.000 claims description 8
- 230000003176 fibrotic effect Effects 0.000 claims description 7
- OUQVKRKGTAUJQA-UHFFFAOYSA-N n-[(1-chloro-4-hydroxyisoquinolin-3-yl)carbonyl]glycine Chemical compound C1=CC=CC2=C(O)C(C(=O)NCC(=O)O)=NC(Cl)=C21 OUQVKRKGTAUJQA-UHFFFAOYSA-N 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 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 4
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 4
- WDEHYUGVPBGBKG-UHFFFAOYSA-N 1-chloro-4-hydroxy-n-(2-hydroxyethyl)-7-propan-2-yloxyisoquinoline-3-carboxamide Chemical compound OC1=C(C(=O)NCCO)N=C(Cl)C2=CC(OC(C)C)=CC=C21 WDEHYUGVPBGBKG-UHFFFAOYSA-N 0.000 claims description 3
- 210000003734 kidney Anatomy 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- IWAGGDFROAISJT-UHFFFAOYSA-N 1h-isoquinoline-2-carboxylic acid Chemical compound C1=CC=C2C=CN(C(=O)O)CC2=C1 IWAGGDFROAISJT-UHFFFAOYSA-N 0.000 claims 1
- 229940125782 compound 2 Drugs 0.000 claims 1
- 229940126214 compound 3 Drugs 0.000 claims 1
- 102000004079 Prolyl Hydroxylases Human genes 0.000 abstract description 28
- 108010043005 Prolyl Hydroxylases Proteins 0.000 abstract description 28
- 239000003112 inhibitor Substances 0.000 abstract description 21
- 125000000217 alkyl group Chemical group 0.000 abstract description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 abstract description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 abstract description 3
- 229910052794 bromium Inorganic materials 0.000 abstract description 3
- 230000003389 potentiating effect Effects 0.000 abstract description 3
- 230000007863 steatosis Effects 0.000 abstract description 3
- 231100000240 steatosis hepatitis Toxicity 0.000 abstract description 3
- 125000003545 alkoxy group Chemical group 0.000 abstract 3
- 238000002844 melting Methods 0.000 description 65
- 230000008018 melting Effects 0.000 description 65
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 56
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 43
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- 239000000243 solution Substances 0.000 description 25
- 210000004185 liver Anatomy 0.000 description 24
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 23
- 239000000047 product Substances 0.000 description 20
- 239000000203 mixture Substances 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 229920001436 collagen Polymers 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- 108010035532 Collagen Proteins 0.000 description 14
- 102000008186 Collagen Human genes 0.000 description 14
- 239000003208 petroleum Substances 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 230000010412 perfusion Effects 0.000 description 13
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 12
- 241000700159 Rattus Species 0.000 description 11
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 11
- 238000001727 in vivo Methods 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 239000000126 substance Substances 0.000 description 9
- 230000036570 collagen biosynthesis Effects 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 8
- 239000000651 prodrug Substances 0.000 description 8
- 229940002612 prodrug Drugs 0.000 description 8
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 229950005499 carbon tetrachloride Drugs 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 229960002591 hydroxyproline Drugs 0.000 description 6
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 4
- UUDOEDPNQYWTMU-UHFFFAOYSA-N pentyl 2-aminoacetate Chemical compound CCCCCOC(=O)CN UUDOEDPNQYWTMU-UHFFFAOYSA-N 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 3
- 102000004266 Collagen Type IV Human genes 0.000 description 3
- 108010042086 Collagen Type IV Proteins 0.000 description 3
- 206010016654 Fibrosis Diseases 0.000 description 3
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 3
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 244000309464 bull Species 0.000 description 3
- 150000007942 carboxylates Chemical group 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 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
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 3
- 230000004761 fibrosis Effects 0.000 description 3
- 150000002483 hydrogen compounds Chemical class 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 238000005805 hydroxylation reaction Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 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 3
- 239000002244 precipitate Substances 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 3
- OBTZDIRUQWFRFZ-UHFFFAOYSA-N 2-(5-methylfuran-2-yl)-n-(4-methylphenyl)quinoline-4-carboxamide Chemical compound O1C(C)=CC=C1C1=CC(C(=O)NC=2C=CC(C)=CC=2)=C(C=CC=C2)C2=N1 OBTZDIRUQWFRFZ-UHFFFAOYSA-N 0.000 description 2
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 2
- SWCWDNMHZACKBG-UHFFFAOYSA-N 4-hydroxy-1-oxo-2h-isoquinoline-3-carboxylic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=NC(O)=C21 SWCWDNMHZACKBG-UHFFFAOYSA-N 0.000 description 2
- XTAHQCRCBHEGRP-UHFFFAOYSA-N 4-methylbenzenesulfonic acid;pentyl 2-aminoacetate Chemical compound CCCCCOC(=O)CN.CC1=CC=C(S(O)(=O)=O)C=C1 XTAHQCRCBHEGRP-UHFFFAOYSA-N 0.000 description 2
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical group N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 2
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- 108010050808 Procollagen Proteins 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 150000004703 alkoxides Chemical class 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000003510 anti-fibrotic effect Effects 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000037319 collagen production Effects 0.000 description 2
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 2
- 230000003352 fibrogenic effect Effects 0.000 description 2
- 210000003494 hepatocyte Anatomy 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 230000033444 hydroxylation Effects 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical class ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 229960001412 pentobarbital Drugs 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000008569 process Effects 0.000 description 2
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical class ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical compound C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- QKJMMOXAZPSGCV-UHFFFAOYSA-N 1,6,7-trichloro-4-hydroxyisoquinoline-3-carboxylic acid Chemical compound C1=C(Cl)C(Cl)=CC2=C(O)C(C(=O)O)=NC(Cl)=C21 QKJMMOXAZPSGCV-UHFFFAOYSA-N 0.000 description 1
- NDMFETHQFUOIQX-UHFFFAOYSA-N 1-(3-chloropropyl)imidazolidin-2-one Chemical compound ClCCCN1CCNC1=O NDMFETHQFUOIQX-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
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- NZSBEZMTLFUYJD-UHFFFAOYSA-N methyl 1,6,7-trichloro-4-hydroxyisoquinoline-3-carboxylate Chemical compound C1=C(Cl)C(Cl)=CC2=C(O)C(C(=O)OC)=NC(Cl)=C21 NZSBEZMTLFUYJD-UHFFFAOYSA-N 0.000 description 1
- JCLXQWPJRSUMFT-UHFFFAOYSA-N methyl 1-chloro-4-hydroxyisoquinoline-3-carboxylate Chemical compound C1=CC=CC2=C(O)C(C(=O)OC)=NC(Cl)=C21 JCLXQWPJRSUMFT-UHFFFAOYSA-N 0.000 description 1
- JOURGLFWVLLAPY-UHFFFAOYSA-N methyl 4-hydroxy-1-oxo-2h-isoquinoline-3-carboxylate Chemical compound C1=CC=C2C(O)=C(C(=O)OC)NC(=O)C2=C1 JOURGLFWVLLAPY-UHFFFAOYSA-N 0.000 description 1
- WMQGVBYZDZCNKC-UHFFFAOYSA-N methyl 6,7-dichloro-4-hydroxy-1-oxo-2h-isoquinoline-3-carboxylate Chemical compound ClC1=C(Cl)C=C2C(O)=C(C(=O)OC)NC(=O)C2=C1 WMQGVBYZDZCNKC-UHFFFAOYSA-N 0.000 description 1
- KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical compound COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- VMESOKCXSYNAKD-UHFFFAOYSA-N n,n-dimethylhydroxylamine Chemical compound CN(C)O VMESOKCXSYNAKD-UHFFFAOYSA-N 0.000 description 1
- KWDCBYBOHQWCKS-UHFFFAOYSA-N n-(2-aminoacetyl)-3-hydroxyquinoline-2-carboxamide Chemical class C1=CC=C2C=C(O)C(C(=O)NC(=O)CN)=NC2=C1 KWDCBYBOHQWCKS-UHFFFAOYSA-N 0.000 description 1
- IXAKZRUKCFYOPF-UHFFFAOYSA-N n-(2-hydroxyethyl)isoquinoline-3-carboxamide Chemical compound C1=CC=C2C=NC(C(=O)NCCO)=CC2=C1 IXAKZRUKCFYOPF-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 239000008012 organic excipient Substances 0.000 description 1
- 125000001190 organyl group Chemical group 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- WJQFJVWTEGGZQC-UHFFFAOYSA-N pentyl 2-[(1-chloro-4-hydroxy-6-propan-2-yloxyisoquinoline-3-carbonyl)amino]acetate Chemical compound C1=CC(OC(C)C)=CC2=C(O)C(C(=O)NCC(=O)OCCCCC)=NC(Cl)=C21 WJQFJVWTEGGZQC-UHFFFAOYSA-N 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- YLLIGHVCTUPGEH-UHFFFAOYSA-M potassium;ethanol;hydroxide Chemical compound [OH-].[K+].CCO YLLIGHVCTUPGEH-UHFFFAOYSA-M 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 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
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 230000037387 scars Effects 0.000 description 1
- 210000001626 skin fibroblast Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 210000004500 stellate cell Anatomy 0.000 description 1
- 210000000352 storage cell Anatomy 0.000 description 1
- 239000006228 supernatant Substances 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
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 229940038773 trisodium citrate Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
-
- 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
-
- 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
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- 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
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/14—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- 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
- C07D217/24—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- 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
- C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Urology & Nephrology (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Cardiology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Obesity (AREA)
- Pulmonology (AREA)
- Gastroenterology & Hepatology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Toxicology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19746287A DE19746287A1 (de) | 1997-10-20 | 1997-10-20 | Substituierte Isochinolin-2-Carbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel |
| DE19746287.1 | 1997-10-20 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR19990037182A KR19990037182A (ko) | 1999-05-25 |
| KR100618922B1 true KR100618922B1 (ko) | 2007-04-25 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019980043578A Expired - Lifetime KR100618922B1 (ko) | 1997-10-20 | 1998-10-19 | 치환된이소퀴놀린-3-카복스아미드,이의제조방법및이를포함하는약제학적조성물 |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US6093730A (enExample) |
| EP (2) | EP1538160B1 (enExample) |
| JP (2) | JP3782591B2 (enExample) |
| KR (1) | KR100618922B1 (enExample) |
| CN (1) | CN1117079C (enExample) |
| AR (1) | AR013696A1 (enExample) |
| AT (2) | ATE432940T1 (enExample) |
| AU (1) | AU755714B2 (enExample) |
| BR (1) | BR9804504B1 (enExample) |
| CA (2) | CA2250664A1 (enExample) |
| CZ (1) | CZ337298A3 (enExample) |
| DE (3) | DE19746287A1 (enExample) |
| DK (2) | DK0911340T3 (enExample) |
| ES (2) | ES2245471T3 (enExample) |
| HU (1) | HUP9802422A3 (enExample) |
| ID (1) | ID21115A (enExample) |
| IL (1) | IL126638A0 (enExample) |
| NO (1) | NO312365B1 (enExample) |
| NZ (1) | NZ332363A (enExample) |
| PL (1) | PL192354B1 (enExample) |
| PT (1) | PT911340E (enExample) |
| SG (1) | SG87776A1 (enExample) |
| TR (1) | TR199802106A2 (enExample) |
| ZA (1) | ZA989505B (enExample) |
Families Citing this family (57)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6528649B2 (en) | 2000-05-30 | 2003-03-04 | Neurogen Corporation | Imidazoloisoquinolines |
| US6762318B2 (en) * | 2001-12-03 | 2004-07-13 | Novo Nordisk A/S | Glucagon antagonists |
| JP2005524612A (ja) * | 2001-12-06 | 2005-08-18 | ファイブローゲン、インコーポレーテッド | 内因性エリスロポエチン（ｅｐｏ）を増加させる方法 |
| US8318703B2 (en) | 2001-12-06 | 2012-11-27 | Fibrogen, Inc. | Methods for improving kidney function |
| EP2295060B1 (en) | 2001-12-06 | 2018-10-31 | Fibrogen, Inc. | Treatment or prevention of ischemic or hypoxic conditions |
| US8124582B2 (en) * | 2002-12-06 | 2012-02-28 | Fibrogen, Inc. | Treatment of diabetes |
| US7618940B2 (en) | 2002-12-06 | 2009-11-17 | Fibrogen, Inc. | Fat regulation |
| CN102718708A (zh) * | 2003-06-06 | 2012-10-10 | 菲布罗根有限公司 | 含氮杂芳基化合物及其在增加内源性促红细胞生成素中的用途 |
| US20060251638A1 (en) * | 2003-06-06 | 2006-11-09 | Volkmar Guenzler-Pukall | Cytoprotection through the use of hif hydroxylase inhibitors |
| US8614204B2 (en) * | 2003-06-06 | 2013-12-24 | Fibrogen, Inc. | Enhanced erythropoiesis and iron metabolism |
| US20060276477A1 (en) * | 2005-06-06 | 2006-12-07 | Fibrogen, Inc. | Treatment method for anemia |
| CN101242817B (zh) | 2005-06-15 | 2016-08-31 | 菲布罗根公司 | HIF1α调节剂在治疗癌症中的用途 |
| AU2006326662B2 (en) * | 2005-12-09 | 2011-07-28 | Amgen Inc. | Quinolone based compounds exhibiting prolyl hydroxylase inhibitory activity, and compositions, and uses thereof |
| RU2457204C2 (ru) | 2006-01-27 | 2012-07-27 | Файброджен, Инк. | Цианоизохинолиновые соединения (варианты), фармацевтическая композиция на их основе, способ ингибирования активности гидроксилазы гипоксия-индуцибельного фактора (hif) и способ лечения и/или профилактики состояния, связанного с hif, и/или состояния, связанного с эритропоэтином, и/или анемии |
| WO2007101204A1 (en) * | 2006-02-27 | 2007-09-07 | Alcon Research, Ltd. | Method of treating glaucoma |
| US7745461B1 (en) | 2006-02-27 | 2010-06-29 | Alcon Research, Ltd. | Method of treating dry eye disorders |
| KR100949982B1 (ko) * | 2006-03-30 | 2010-03-29 | 엘지전자 주식회사 | 비디오 신호를 디코딩/인코딩하기 위한 방법 및 장치 |
| AU2007234408B2 (en) | 2006-04-04 | 2011-05-19 | Fibrogen, Inc. | Pyrrolo- and thiazolo-pyridine compounds as HIF modulators |
| DK3026044T3 (en) | 2006-06-26 | 2019-02-18 | Akebia Therapeutics Inc | PROLYL HYDROXYLASE INHIBITORS AND METHODS FOR USE |
| ES2393326T3 (es) | 2006-12-18 | 2012-12-20 | Amgen, Inc | Compuestos basados en azaquinolona que presentan actividad inhibidora de prolil hidroxilasas, composiciones y usos de los mismos |
| CA2672656C (en) | 2006-12-18 | 2012-03-20 | Amgen Inc. | Naphthalenone compounds exhibiting prolyl hydroxylase inhibitory activity, compositions, and uses thereof |
| EP2155680B1 (en) | 2007-04-18 | 2013-12-04 | Amgen, Inc | Indanone derivatives that inhibit prolyl hydroxylase |
| CA2683956C (en) | 2007-04-18 | 2012-12-18 | Amgen Inc. | Quinolones and azaquinolones that inhibit prolyl hydroxylase |
| AU2008248165B2 (en) | 2007-05-04 | 2011-12-08 | Amgen Inc. | Diazaquinolones that inhibit prolyl hydroxylase activity |
| EP2150251B9 (en) | 2007-05-04 | 2013-02-27 | Amgen, Inc | Thienopyridine and thiazolopyridine derivatives that inhibit prolyl hydroxylase activity |
| US8962530B2 (en) * | 2007-06-27 | 2015-02-24 | Regents Of The University Of Colorado | Inflammatory bowel disease therapies |
| CN101497584B (zh) * | 2008-01-29 | 2010-12-22 | 首都医科大学 | 异喹啉-3-甲酰氨基酸苄酯及其制备和应用 |
| HRP20141038T2 (hr) | 2008-04-28 | 2015-07-03 | Janssen Pharmaceutica N.V. | Benzoimidazoli kao inhibitori prolil hidroksilaze |
| CN105037323A (zh) | 2008-11-14 | 2015-11-11 | 菲布罗根有限公司 | 作为hif羟化酶抑制剂的苯并噻喃衍生物 |
| HRP20140705T1 (hr) * | 2009-07-17 | 2014-09-12 | Japan Tobacco, Inc. | Spoj triazolopiridina i njegovo djelovanje kao inhibitora prolil hidroksilaze i induktora proizvodnje eritropoetina |
| NO2686520T3 (enExample) | 2011-06-06 | 2018-03-17 | ||
| KR102029951B1 (ko) * | 2011-07-22 | 2019-11-08 | 베이징 베타 파머수티컬 컴퍼니 리미티드 | 프로릴 히드록실라제 억제제로서 화합물의 다형체형, 및 이의 용도 |
| MX368157B (es) | 2011-10-25 | 2019-09-20 | Janssen Pharmaceutica Nv | Formulaciones de sal de meglumina del acido 1-(5,6-dicloro-1h-benz o[d]imidazol-2-il)-1h-pirazol-4-carboxilico. |
| JP6129217B2 (ja) | 2012-03-09 | 2017-05-17 | フィブロジェン インコーポレイテッド | Ｈｉｆヒドロキシラーゼインヒビターとしての４−ヒドロキシ−イソキノリン化合物 |
| KR20220164068A (ko) | 2012-07-16 | 2022-12-12 | 피브로겐, 인크. | 프롤릴 하이드록실라제 억제제 [(4-하이드록시-1-메틸-7-페녹시-아이소퀴놀린-3-카보닐)-아미노]-아세트산의 결정형 |
| US8883823B2 (en) | 2012-07-16 | 2014-11-11 | Fibrogen, Inc. | Crystalline forms of a prolyl hydroxylase inhibitor |
| ES2631655T3 (es) * | 2012-07-16 | 2017-09-01 | Fibrogen, Inc. | Procedimiento para fabricar compuestos de isoquinolina |
| US9822135B2 (en) | 2012-10-30 | 2017-11-21 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | STAT3 dimerization inhibitors |
| DK2951159T3 (en) | 2013-01-24 | 2018-11-19 | Fibrogen Inc | CRYSTALLIC FORMS OF {[1-CYANO-5- (4-CHLORPHENOXY) -4-HYDROXY-ISOQUINOLIN-3-CARBONYL] -AMINO} ACETIC ACID |
| LT3003284T (lt) | 2013-06-06 | 2020-04-27 | Fibrogen, Inc. | Hif hidroksilazės inhibitoriaus farmacinės kompozicijos |
| DK3007695T3 (da) | 2013-06-13 | 2024-03-18 | Akebia Therapeutics Inc | Sammensætninger og fremgangsmåder til behandling af anæmi |
| SG10202012791TA (en) | 2013-11-15 | 2021-01-28 | Akebia Therapeutics Inc | Solid forms of {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, compositions, and uses thereof |
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