MX2008009581A - Compuestos de cianoisoquinolina que estabilizan el factor inducible hipoxia (fih). - Google Patents
Compuestos de cianoisoquinolina que estabilizan el factor inducible hipoxia (fih).Info
- Publication number
- MX2008009581A MX2008009581A MX2008009581A MX2008009581A MX2008009581A MX 2008009581 A MX2008009581 A MX 2008009581A MX 2008009581 A MX2008009581 A MX 2008009581A MX 2008009581 A MX2008009581 A MX 2008009581A MX 2008009581 A MX2008009581 A MX 2008009581A
- Authority
- MX
- Mexico
- Prior art keywords
- isoquinoline
- hydroxy
- cyano
- amino
- carbonyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 66
- HJHXYSBRTVFEDD-UHFFFAOYSA-N isoquinoline-1-carbonitrile Chemical class C1=CC=C2C(C#N)=NC=CC2=C1 HJHXYSBRTVFEDD-UHFFFAOYSA-N 0.000 title abstract description 4
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 claims abstract description 41
- 108090000394 Erythropoietin Proteins 0.000 claims abstract description 40
- 102000003951 Erythropoietin Human genes 0.000 claims abstract description 40
- 229940105423 erythropoietin Drugs 0.000 claims abstract description 40
- 206010021143 Hypoxia Diseases 0.000 claims abstract description 13
- 230000007954 hypoxia Effects 0.000 claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims description 443
- 239000000203 mixture Substances 0.000 claims description 267
- -1 cyano, hydroxyl Chemical group 0.000 claims description 237
- 239000002253 acid Substances 0.000 claims description 168
- 125000001072 heteroaryl group Chemical group 0.000 claims description 82
- 239000001257 hydrogen Substances 0.000 claims description 79
- 229910052739 hydrogen Inorganic materials 0.000 claims description 79
- 125000000217 alkyl group Chemical group 0.000 claims description 55
- 125000003118 aryl group Chemical group 0.000 claims description 55
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 52
- 125000003107 substituted aryl group Chemical group 0.000 claims description 46
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 44
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 40
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 38
- 208000007502 anemia Diseases 0.000 claims description 34
- 150000002431 hydrogen Chemical group 0.000 claims description 32
- 150000003839 salts Chemical class 0.000 claims description 28
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 27
- 108090000623 proteins and genes Proteins 0.000 claims description 24
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 claims description 22
- 125000004104 aryloxy group Chemical group 0.000 claims description 22
- 125000005843 halogen group Chemical group 0.000 claims description 22
- 108010074633 Mixed Function Oxygenases Proteins 0.000 claims description 20
- 102000008109 Mixed Function Oxygenases Human genes 0.000 claims description 20
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 239000000651 prodrug Substances 0.000 claims description 16
- 229940002612 prodrug Drugs 0.000 claims description 16
- 230000000302 ischemic effect Effects 0.000 claims description 14
- 239000012453 solvate Substances 0.000 claims description 14
- 102000004169 proteins and genes Human genes 0.000 claims description 13
- 102000004190 Enzymes Human genes 0.000 claims description 12
- 108090000790 Enzymes Proteins 0.000 claims description 12
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 12
- 208000028867 ischemia Diseases 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 125000001188 haloalkyl group Chemical group 0.000 claims description 11
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 10
- 230000000694 effects Effects 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 125000005605 benzo group Chemical group 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 108010043005 Prolyl Hydroxylases Proteins 0.000 claims description 7
- 102000004079 Prolyl Hydroxylases Human genes 0.000 claims description 7
- 230000001684 chronic effect Effects 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 7
- 101000881648 Homo sapiens Egl nine homolog 1 Proteins 0.000 claims description 6
- 101000881650 Homo sapiens Prolyl hydroxylase EGLN2 Proteins 0.000 claims description 6
- 208000010378 Pulmonary Embolism Diseases 0.000 claims description 6
- 230000001154 acute effect Effects 0.000 claims description 6
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 claims description 6
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 5
- 206010019280 Heart failures Diseases 0.000 claims description 5
- 101000881678 Homo sapiens Prolyl hydroxylase EGLN3 Proteins 0.000 claims description 5
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- PDQRQJVPEFGVRK-UHFFFAOYSA-N 2,1,3-benzothiadiazole Chemical compound C1=CC=CC2=NSN=C21 PDQRQJVPEFGVRK-UHFFFAOYSA-N 0.000 claims description 4
- 206010054936 Cardiac cirrhosis Diseases 0.000 claims description 4
- 101000987586 Homo sapiens Eosinophil peroxidase Proteins 0.000 claims description 4
- 101000920686 Homo sapiens Erythropoietin Proteins 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 208000020832 chronic kidney disease Diseases 0.000 claims description 4
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 4
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 claims description 4
- 230000010437 erythropoiesis Effects 0.000 claims description 4
- 102000044890 human EPO Human genes 0.000 claims description 4
- 229910000359 iron(II) sulfate Inorganic materials 0.000 claims description 4
- ISUSJVGCVSHSAK-UHFFFAOYSA-N methyl 2-[(1-cyano-4-methoxy-8-phenoxyisoquinoline-3-carbonyl)amino]acetate Chemical compound C=1C=CC2=C(OC)C(C(=O)NCC(=O)OC)=NC(C#N)=C2C=1OC1=CC=CC=C1 ISUSJVGCVSHSAK-UHFFFAOYSA-N 0.000 claims description 4
- 208000010125 myocardial infarction Diseases 0.000 claims description 4
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 4
- 125000005338 substituted cycloalkoxy group Chemical group 0.000 claims description 4
- 230000000451 tissue damage Effects 0.000 claims description 4
- 231100000827 tissue damage Toxicity 0.000 claims description 4
- XFDRTANSBXAQCX-ZETCQYMHSA-N (2s)-2-[(1-cyano-4-hydroxyisoquinoline-3-carbonyl)amino]propanoic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)N[C@@H](C)C(O)=O)=NC(C#N)=C21 XFDRTANSBXAQCX-ZETCQYMHSA-N 0.000 claims description 3
- MSQZIWYFGGVXFP-UHFFFAOYSA-N 2-[(1-cyano-4-hydroxy-6-methoxyisoquinoline-3-carbonyl)amino]acetic acid Chemical compound N#CC1=NC(C(=O)NCC(O)=O)=C(O)C2=CC(OC)=CC=C21 MSQZIWYFGGVXFP-UHFFFAOYSA-N 0.000 claims description 3
- MSKIZMMYIZHWCR-UHFFFAOYSA-N 2-[(6-chloro-1-cyano-4-hydroxyisoquinoline-3-carbonyl)amino]acetic acid Chemical compound C1=CC(Cl)=CC2=C(O)C(C(=O)NCC(=O)O)=NC(C#N)=C21 MSKIZMMYIZHWCR-UHFFFAOYSA-N 0.000 claims description 3
- 206010022657 Intestinal infarction Diseases 0.000 claims description 3
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 claims description 3
- 229930003779 Vitamin B12 Natural products 0.000 claims description 3
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 claims description 3
- 235000003891 ferrous sulphate Nutrition 0.000 claims description 3
- 239000011790 ferrous sulphate Substances 0.000 claims description 3
- 235000019152 folic acid Nutrition 0.000 claims description 3
- 239000011724 folic acid Substances 0.000 claims description 3
- 229960000304 folic acid Drugs 0.000 claims description 3
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 claims description 3
- 229940124597 therapeutic agent Drugs 0.000 claims description 3
- 235000019163 vitamin B12 Nutrition 0.000 claims description 3
- 239000011715 vitamin B12 Substances 0.000 claims description 3
- OINOLIGLRWFXAH-LLVKDONJSA-N (2r)-2-[(1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carbonyl)amino]propanoic acid Chemical compound C1=CC2=C(O)C(C(=O)N[C@H](C)C(O)=O)=NC(C#N)=C2C=C1OC1=CC=CC=C1 OINOLIGLRWFXAH-LLVKDONJSA-N 0.000 claims description 2
- HEEJNIOLTLADLS-LLVKDONJSA-N (2r)-2-[(1-cyano-4-hydroxy-8-phenoxyisoquinoline-3-carbonyl)amino]propanoic acid Chemical compound C=1C=CC2=C(O)C(C(=O)N[C@H](C)C(O)=O)=NC(C#N)=C2C=1OC1=CC=CC=C1 HEEJNIOLTLADLS-LLVKDONJSA-N 0.000 claims description 2
- PDZURKICFJDDOM-UHFFFAOYSA-N 2-[(1-cyano-4,7-dihydroxyisoquinoline-3-carbonyl)amino]acetic acid Chemical compound C1=C(O)C=CC2=C(O)C(C(=O)NCC(=O)O)=NC(C#N)=C21 PDZURKICFJDDOM-UHFFFAOYSA-N 0.000 claims description 2
- QHLJEZMZQWUWAF-UHFFFAOYSA-N 2-[(1-cyano-4-hydroxy-7-methoxyisoquinoline-3-carbonyl)amino]acetic acid Chemical compound OC1=C(C(=O)NCC(O)=O)N=C(C#N)C2=CC(OC)=CC=C21 QHLJEZMZQWUWAF-UHFFFAOYSA-N 0.000 claims description 2
- RMTMNJJBCKGPBK-UHFFFAOYSA-N 2-[(1-cyano-4-methoxy-8-phenoxyisoquinoline-3-carbonyl)amino]acetic acid Chemical compound C1=CC=C2C(OC)=C(C(=O)NCC(O)=O)N=C(C#N)C2=C1OC1=CC=CC=C1 RMTMNJJBCKGPBK-UHFFFAOYSA-N 0.000 claims description 2
- 101100203602 Hypocrea jecorina (strain QM6a) sor7 gene Proteins 0.000 claims description 2
- 206010061481 Renal injury Diseases 0.000 claims description 2
- 208000022831 chronic renal failure syndrome Diseases 0.000 claims description 2
- 102000053692 human EGLN1 Human genes 0.000 claims description 2
- 208000002780 macular degeneration Diseases 0.000 claims description 2
- 230000010410 reperfusion Effects 0.000 claims description 2
- 230000000638 stimulation Effects 0.000 claims description 2
- FQAPENLFTOTTGL-UHFFFAOYSA-N 2-[(1-cyano-4-hydroxy-8-phenylisoquinoline-3-carbonyl)amino]acetic acid Chemical compound C=1C=CC2=C(O)C(C(=O)NCC(=O)O)=NC(C#N)=C2C=1C1=CC=CC=C1 FQAPENLFTOTTGL-UHFFFAOYSA-N 0.000 claims 1
- DRSMTYDBAZUBFH-UHFFFAOYSA-N 2-[[1-cyano-4-hydroxy-8-(2-methoxyphenoxy)isoquinoline-3-carbonyl]amino]acetic acid Chemical compound COC1=CC=CC=C1OC1=CC=CC2=C(O)C(C(=O)NCC(O)=O)=NC(C#N)=C12 DRSMTYDBAZUBFH-UHFFFAOYSA-N 0.000 claims 1
- 239000005977 Ethylene Substances 0.000 claims 1
- 102000048660 human EGLN2 Human genes 0.000 claims 1
- 102000050122 human EGLN3 Human genes 0.000 claims 1
- 230000008929 regeneration Effects 0.000 claims 1
- 238000011069 regeneration method Methods 0.000 claims 1
- 230000001939 inductive effect Effects 0.000 abstract description 3
- 230000001404 mediated effect Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 351
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 185
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 156
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 140
- 235000019439 ethyl acetate Nutrition 0.000 description 124
- 239000007787 solid Substances 0.000 description 107
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 106
- 239000000243 solution Substances 0.000 description 94
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 73
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 68
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 60
- 239000000741 silica gel Substances 0.000 description 59
- 229910002027 silica gel Inorganic materials 0.000 description 59
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 56
- 239000004471 Glycine Substances 0.000 description 54
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 54
- 238000006243 chemical reaction Methods 0.000 description 54
- 229960002449 glycine Drugs 0.000 description 54
- 125000000623 heterocyclic group Chemical group 0.000 description 51
- 238000005481 NMR spectroscopy Methods 0.000 description 50
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 49
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 48
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 48
- 238000003756 stirring Methods 0.000 description 46
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 44
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
- 239000012267 brine Substances 0.000 description 40
- 238000003818 flash chromatography Methods 0.000 description 40
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 40
- 239000012044 organic layer Substances 0.000 description 39
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 37
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 36
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 35
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 34
- 238000001914 filtration Methods 0.000 description 32
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 31
- 238000000746 purification Methods 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
- 238000007796 conventional method Methods 0.000 description 28
- 239000003921 oil Substances 0.000 description 28
- 235000019198 oils Nutrition 0.000 description 28
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 27
- 235000019341 magnesium sulphate Nutrition 0.000 description 27
- 239000012074 organic phase Substances 0.000 description 27
- 238000004587 chromatography analysis Methods 0.000 description 25
- 239000000706 filtrate Substances 0.000 description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 23
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 22
- 125000004494 ethyl ester group Chemical group 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 238000001816 cooling Methods 0.000 description 21
- 238000000605 extraction Methods 0.000 description 21
- 238000006386 neutralization reaction Methods 0.000 description 21
- 239000002244 precipitate Substances 0.000 description 21
- 238000001556 precipitation Methods 0.000 description 21
- 239000002904 solvent Substances 0.000 description 21
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 19
- 239000002585 base Substances 0.000 description 19
- 229910000027 potassium carbonate Inorganic materials 0.000 description 19
- 238000010992 reflux Methods 0.000 description 19
- 239000000725 suspension Substances 0.000 description 19
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 208000035475 disorder Diseases 0.000 description 17
- 125000001424 substituent group Chemical group 0.000 description 17
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 16
- 125000004432 carbon atom Chemical group C* 0.000 description 16
- 238000002955 isolation Methods 0.000 description 16
- 239000010410 layer Substances 0.000 description 16
- 150000004702 methyl esters Chemical class 0.000 description 16
- 229910052757 nitrogen Inorganic materials 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 239000003153 chemical reaction reagent Substances 0.000 description 15
- 150000002148 esters Chemical class 0.000 description 15
- 229920006395 saturated elastomer Polymers 0.000 description 15
- 238000011282 treatment Methods 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 14
- 235000011181 potassium carbonates Nutrition 0.000 description 14
- 235000017557 sodium bicarbonate Nutrition 0.000 description 14
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 14
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 14
- 239000004342 Benzoyl peroxide Substances 0.000 description 13
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 13
- 235000019400 benzoyl peroxide Nutrition 0.000 description 13
- 238000005859 coupling reaction Methods 0.000 description 13
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 235000018102 proteins Nutrition 0.000 description 12
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 125000003342 alkenyl group Chemical group 0.000 description 11
- 125000000304 alkynyl group Chemical group 0.000 description 11
- 239000000460 chlorine Substances 0.000 description 11
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 11
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 10
- 238000007792 addition Methods 0.000 description 10
- 229940024606 amino acid Drugs 0.000 description 10
- 235000001014 amino acid Nutrition 0.000 description 10
- 150000001413 amino acids Chemical class 0.000 description 10
- 229910052801 chlorine Inorganic materials 0.000 description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
- 238000009472 formulation Methods 0.000 description 10
- 239000012634 fragment Substances 0.000 description 10
- 125000005017 substituted alkenyl group Chemical group 0.000 description 10
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 10
- KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical compound OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- 238000003556 assay Methods 0.000 description 9
- 229910052794 bromium Inorganic materials 0.000 description 9
- 230000008878 coupling Effects 0.000 description 9
- 238000010168 coupling process Methods 0.000 description 9
- 125000004093 cyano group Chemical group *C#N 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 9
- 108090000765 processed proteins & peptides Proteins 0.000 description 9
- 125000004426 substituted alkynyl group Chemical group 0.000 description 9
- 239000003826 tablet Substances 0.000 description 9
- 239000011701 zinc Substances 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 8
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 8
- 229910000024 caesium carbonate Inorganic materials 0.000 description 8
- 150000004820 halides Chemical class 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 208000014674 injury Diseases 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- NDMFETHQFUOIQX-UHFFFAOYSA-N 1-(3-chloropropyl)imidazolidin-2-one Chemical compound ClCCCN1CCNC1=O NDMFETHQFUOIQX-UHFFFAOYSA-N 0.000 description 7
- 229910019201 POBr3 Inorganic materials 0.000 description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
- 239000006184 cosolvent Substances 0.000 description 7
- 239000003480 eluent Substances 0.000 description 7
- 238000010828 elution Methods 0.000 description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 description 7
- 229910052760 oxygen Inorganic materials 0.000 description 7
- 239000001301 oxygen Substances 0.000 description 7
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 7
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 7
- 238000001356 surgical procedure Methods 0.000 description 7
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- 102100037249 Egl nine homolog 1 Human genes 0.000 description 6
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 6
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 239000000969 carrier Substances 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 239000008121 dextrose Substances 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 229910052740 iodine Inorganic materials 0.000 description 6
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 235000015424 sodium Nutrition 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 229910052725 zinc Inorganic materials 0.000 description 6
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
- 239000005711 Benzoic acid Substances 0.000 description 5
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 5
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 5
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- 101100109871 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) aro-8 gene Proteins 0.000 description 5
- 102100037248 Prolyl hydroxylase EGLN2 Human genes 0.000 description 5
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 5
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 5
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 5
- 208000027418 Wounds and injury Diseases 0.000 description 5
- 125000004414 alkyl thio group Chemical group 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 230000003197 catalytic effect Effects 0.000 description 5
- 238000004113 cell culture Methods 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 239000006071 cream Substances 0.000 description 5
- 206010012601 diabetes mellitus Diseases 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 210000003743 erythrocyte Anatomy 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- 125000005844 heterocyclyloxy group Chemical group 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 230000002209 hydrophobic effect Effects 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 5
- 125000006239 protecting group Chemical group 0.000 description 5
- 102200145454 rs121908575 Human genes 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- YRAJNWYBUCUFBD-UHFFFAOYSA-N 2,2,6,6-tetramethylheptane-3,5-dione Chemical compound CC(C)(C)C(=O)CC(=O)C(C)(C)C YRAJNWYBUCUFBD-UHFFFAOYSA-N 0.000 description 4
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 4
- ASSKVPFEZFQQNQ-UHFFFAOYSA-N 2-benzoxazolinone Chemical compound C1=CC=C2OC(O)=NC2=C1 ASSKVPFEZFQQNQ-UHFFFAOYSA-N 0.000 description 4
- NTZMSBAAHBICLE-UHFFFAOYSA-N 4-nitrobenzene-1,2-dicarbonitrile Chemical compound [O-][N+](=O)C1=CC=C(C#N)C(C#N)=C1 NTZMSBAAHBICLE-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 4
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 4
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- 102100037247 Prolyl hydroxylase EGLN3 Human genes 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 4
- 125000005110 aryl thio group Chemical group 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 238000002512 chemotherapy Methods 0.000 description 4
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 4
- 229960004316 cisplatin Drugs 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 125000005366 cycloalkylthio group Chemical group 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 125000001153 fluoro group Chemical group F* 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 229940014259 gelatin Drugs 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- 230000014509 gene expression Effects 0.000 description 4
- 125000005368 heteroarylthio group Chemical group 0.000 description 4
- 239000003701 inert diluent Substances 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- XOHWAYZKTGAGFI-UHFFFAOYSA-N methyl 4-hydroxy-8-iodoisoquinoline-3-carboxylate Chemical compound IC1=CC=CC2=C(O)C(C(=O)OC)=NC=C21 XOHWAYZKTGAGFI-UHFFFAOYSA-N 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 4
- 150000002989 phenols Chemical class 0.000 description 4
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 4
- 230000036470 plasma concentration Effects 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- 235000009518 sodium iodide Nutrition 0.000 description 4
- 239000000600 sorbitol Substances 0.000 description 4
- 239000003381 stabilizer Substances 0.000 description 4
- 238000013268 sustained release Methods 0.000 description 4
- 239000012730 sustained-release form Substances 0.000 description 4
- 230000008733 trauma Effects 0.000 description 4
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 4
- 229960002555 zidovudine Drugs 0.000 description 4
- LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 description 3
- CHZFBCOJLDUOSX-UHFFFAOYSA-N 2-[(1-cyano-4-hydroxy-7-phenylmethoxyisoquinoline-3-carbonyl)amino]acetic acid Chemical compound C1=CC2=C(O)C(C(=O)NCC(=O)O)=NC(C#N)=C2C=C1OCC1=CC=CC=C1 CHZFBCOJLDUOSX-UHFFFAOYSA-N 0.000 description 3
- ASHGTJPOSUFTGB-UHFFFAOYSA-N 3-methoxyphenol Chemical compound COC1=CC=CC(O)=C1 ASHGTJPOSUFTGB-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- 208000032467 Aplastic anaemia Diseases 0.000 description 3
- 108010011485 Aspartame Proteins 0.000 description 3
- 101000810443 Caenorhabditis elegans Hypoxia-inducible factor prolyl hydroxylase Proteins 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 3
- 229930091371 Fructose Natural products 0.000 description 3
- 239000005715 Fructose Substances 0.000 description 3
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 108010054147 Hemoglobins Proteins 0.000 description 3
- 102000001554 Hemoglobins Human genes 0.000 description 3
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- 239000005913 Maltodextrin Substances 0.000 description 3
- 229920002774 Maltodextrin Polymers 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- 238000007126 N-alkylation reaction Methods 0.000 description 3
- 208000012902 Nervous system disease Diseases 0.000 description 3
- 208000025966 Neurological disease Diseases 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 125000004442 acylamino group Chemical group 0.000 description 3
- 229960003767 alanine Drugs 0.000 description 3
- 125000000266 alpha-aminoacyl group Chemical group 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 239000006286 aqueous extract Substances 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 125000005325 aryloxy aryl group Chemical group 0.000 description 3
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 3
- 239000000605 aspartame Substances 0.000 description 3
- 235000010357 aspartame Nutrition 0.000 description 3
- 229960003438 aspartame Drugs 0.000 description 3
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
- 239000012455 biphasic mixture Substances 0.000 description 3
- 150000001718 carbodiimides Chemical class 0.000 description 3
- 229910002092 carbon dioxide Inorganic materials 0.000 description 3
- 235000010980 cellulose Nutrition 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 238000005538 encapsulation Methods 0.000 description 3
- LSZMTHMYAQITSD-UHFFFAOYSA-N ethyl 3-iodo-2-methylbenzoate Chemical compound CCOC(=O)C1=CC=CC(I)=C1C LSZMTHMYAQITSD-UHFFFAOYSA-N 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical compound COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 230000026030 halogenation Effects 0.000 description 3
- 238000005658 halogenation reaction Methods 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 125000001183 hydrocarbyl group Chemical group 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 125000005647 linker group Chemical group 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 229940035034 maltodextrin Drugs 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 235000015320 potassium carbonate Nutrition 0.000 description 3
- 238000001959 radiotherapy Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 102200142046 rs727503778 Human genes 0.000 description 3
- 239000012047 saturated solution Substances 0.000 description 3
- 239000001632 sodium acetate Substances 0.000 description 3
- 235000017281 sodium acetate Nutrition 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 229940032147 starch Drugs 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- RKHXQBLJXBGEKF-UHFFFAOYSA-M tetrabutylphosphanium;bromide Chemical compound [Br-].CCCC[P+](CCCC)(CCCC)CCCC RKHXQBLJXBGEKF-UHFFFAOYSA-M 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- XLHUBROMZOAQMV-UHFFFAOYSA-N 1,4-benzosemiquinone Chemical group [O]C1=CC=C(O)C=C1 XLHUBROMZOAQMV-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- UMVNOZDXDVGKQG-UHFFFAOYSA-N 1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxylic acid Chemical compound C1=CC2=C(O)C(C(=O)O)=NC(C#N)=C2C=C1OC1=CC=CC=C1 UMVNOZDXDVGKQG-UHFFFAOYSA-N 0.000 description 2
- XZXVTYFCVFXPHW-UHFFFAOYSA-N 1-cyano-4-methoxy-8-phenoxyisoquinoline-3-carboxylic acid Chemical compound C1=CC=C2C(OC)=C(C(O)=O)N=C(C#N)C2=C1OC1=CC=CC=C1 XZXVTYFCVFXPHW-UHFFFAOYSA-N 0.000 description 2
- SULYEHHGGXARJS-UHFFFAOYSA-N 2',4'-dihydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C=C1O SULYEHHGGXARJS-UHFFFAOYSA-N 0.000 description 2
- HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 description 2
- LWRSYTXEQUUTKW-UHFFFAOYSA-N 2,4-dimethoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C(OC)=C1 LWRSYTXEQUUTKW-UHFFFAOYSA-N 0.000 description 2
- NXXYKOUNUYWIHA-UHFFFAOYSA-N 2,6-Dimethylphenol Chemical compound CC1=CC=CC(C)=C1O NXXYKOUNUYWIHA-UHFFFAOYSA-N 0.000 description 2
- YAVZBKUGEUTUQQ-UHFFFAOYSA-N 2-(4-fluorophenoxy)-6-methylbenzoic acid Chemical compound CC1=CC=CC(OC=2C=CC(F)=CC=2)=C1C(O)=O YAVZBKUGEUTUQQ-UHFFFAOYSA-N 0.000 description 2
- WKODVHXLMTZJHB-UHFFFAOYSA-N 2-(dimethylamino)-1,3-benzoxazol-5-ol Chemical compound OC1=CC=C2OC(N(C)C)=NC2=C1 WKODVHXLMTZJHB-UHFFFAOYSA-N 0.000 description 2
- OOVXTEHRWZLELV-UHFFFAOYSA-N 2-[(1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carbonyl)amino]acetic acid Chemical compound C1=CC2=C(O)C(C(=O)NCC(=O)O)=NC(C#N)=C2C=C1OC1=CC=CC=C1 OOVXTEHRWZLELV-UHFFFAOYSA-N 0.000 description 2
- ZEJZLPSYVPTCTJ-UHFFFAOYSA-N 2-[(1-cyano-4-hydroxy-7-propan-2-yloxyisoquinoline-3-carbonyl)amino]acetic acid Chemical compound OC1=C(C(=O)NCC(O)=O)N=C(C#N)C2=CC(OC(C)C)=CC=C21 ZEJZLPSYVPTCTJ-UHFFFAOYSA-N 0.000 description 2
- LQINZCHSUDFFAO-UHFFFAOYSA-N 2-[(1-cyano-4-hydroxy-8-phenoxyisoquinoline-3-carbonyl)amino]acetic acid Chemical compound C=1C=CC2=C(O)C(C(=O)NCC(=O)O)=NC(C#N)=C2C=1OC1=CC=CC=C1 LQINZCHSUDFFAO-UHFFFAOYSA-N 0.000 description 2
- TUQCVWJJKJPEKG-UHFFFAOYSA-N 2-[(1-cyano-6-cyclohexyloxy-4-hydroxyisoquinoline-3-carbonyl)amino]acetic acid Chemical compound C=1C2=C(O)C(C(=O)NCC(=O)O)=NC(C#N)=C2C=CC=1OC1CCCCC1 TUQCVWJJKJPEKG-UHFFFAOYSA-N 0.000 description 2
- WBLKKRDZVHEAAU-UHFFFAOYSA-N 2-[(7-benzyl-1-cyano-4-hydroxyisoquinoline-3-carbonyl)amino]acetic acid Chemical compound C1=CC2=C(O)C(C(=O)NCC(=O)O)=NC(C#N)=C2C=C1CC1=CC=CC=C1 WBLKKRDZVHEAAU-UHFFFAOYSA-N 0.000 description 2
- NCKKNOJKNWHOJY-UHFFFAOYSA-N 2-[1,3-dioxo-5-(2,4,6-trimethylphenoxy)isoindol-2-yl]acetic acid Chemical compound CC1=CC(C)=CC(C)=C1OC1=CC=C(C(=O)N(CC(O)=O)C2=O)C2=C1 NCKKNOJKNWHOJY-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- POYRFRAARYXDDR-UHFFFAOYSA-N 2-[5-(2,6-dimethylphenoxy)-1,3-dioxoisoindol-2-yl]acetic acid Chemical compound CC1=CC=CC(C)=C1OC1=CC=C(C(=O)N(CC(O)=O)C2=O)C2=C1 POYRFRAARYXDDR-UHFFFAOYSA-N 0.000 description 2
- VPWNKEZZXCFUOD-UHFFFAOYSA-N 2-[5-(2-ethyl-6-methylphenoxy)-1,3-dioxoisoindol-2-yl]acetic acid Chemical compound CCC1=CC=CC(C)=C1OC1=CC=C(C(=O)N(CC(O)=O)C2=O)C2=C1 VPWNKEZZXCFUOD-UHFFFAOYSA-N 0.000 description 2
- DNEKRRNZOCTAHX-UHFFFAOYSA-N 2-[5-(4-chloro-2,6-dimethylphenoxy)-1,3-dioxoisoindol-2-yl]acetic acid Chemical compound CC1=CC(Cl)=CC(C)=C1OC1=CC=C(C(=O)N(CC(O)=O)C2=O)C2=C1 DNEKRRNZOCTAHX-UHFFFAOYSA-N 0.000 description 2
- AHEVSKSJZFZUDM-UHFFFAOYSA-N 2-[[6-(benzenesulfonyl)-1-cyano-4-hydroxyisoquinoline-3-carbonyl]amino]acetic acid Chemical compound C=1C2=C(O)C(C(=O)NCC(=O)O)=NC(C#N)=C2C=CC=1S(=O)(=O)C1=CC=CC=C1 AHEVSKSJZFZUDM-UHFFFAOYSA-N 0.000 description 2
- BRENVJPPZRBCPU-UHFFFAOYSA-N 2-chloro-5-methoxy-1,3-benzoxazole Chemical compound COC1=CC=C2OC(Cl)=NC2=C1 BRENVJPPZRBCPU-UHFFFAOYSA-N 0.000 description 2
- CEFMMQYDPGCYMG-UHFFFAOYSA-N 2-chloro-6-methylbenzoic acid Chemical compound CC1=CC=CC(Cl)=C1C(O)=O CEFMMQYDPGCYMG-UHFFFAOYSA-N 0.000 description 2
- ROFBPPIQUBJMRO-UHFFFAOYSA-N 2-methyl-1,3-benzothiazol-6-ol Chemical compound C1=C(O)C=C2SC(C)=NC2=C1 ROFBPPIQUBJMRO-UHFFFAOYSA-N 0.000 description 2
- XGNKIHYPOWUMKL-UHFFFAOYSA-N 3-iodo-2-methylbenzoic acid Chemical compound CC1=C(I)C=CC=C1C(O)=O XGNKIHYPOWUMKL-UHFFFAOYSA-N 0.000 description 2
- LSGGYJSFXWIQSG-UHFFFAOYSA-N 4-(2,3-dihydro-1-benzofuran-5-yloxy)benzene-1,2-dicarbonitrile Chemical compound C1=C(C#N)C(C#N)=CC=C1OC1=CC=C(OCC2)C2=C1 LSGGYJSFXWIQSG-UHFFFAOYSA-N 0.000 description 2
- NDVDLOOLZCCDSX-UHFFFAOYSA-N 4-(2,3-dihydro-1-benzofuran-5-yloxy)phthalic acid Chemical compound C1=C(C(O)=O)C(C(=O)O)=CC=C1OC1=CC=C(OCC2)C2=C1 NDVDLOOLZCCDSX-UHFFFAOYSA-N 0.000 description 2
- KXTSZASJZQWWKF-UHFFFAOYSA-N 4-(2,4,6-trimethylphenoxy)benzene-1,2-dicarbonitrile Chemical compound CC1=CC(C)=CC(C)=C1OC1=CC=C(C#N)C(C#N)=C1 KXTSZASJZQWWKF-UHFFFAOYSA-N 0.000 description 2
- LBOGTHWAXKRWJA-UHFFFAOYSA-N 4-(2-ethyl-6-methylphenoxy)benzene-1,2-dicarbonitrile Chemical compound CCC1=CC=CC(C)=C1OC1=CC=C(C#N)C(C#N)=C1 LBOGTHWAXKRWJA-UHFFFAOYSA-N 0.000 description 2
- UZXAQYLNUKMZDQ-UHFFFAOYSA-N 4-(4-phenylmethoxyphenoxy)benzene-1,2-dicarbonitrile Chemical compound C1=C(C#N)C(C#N)=CC=C1OC(C=C1)=CC=C1OCC1=CC=CC=C1 UZXAQYLNUKMZDQ-UHFFFAOYSA-N 0.000 description 2
- AQHKULBPGOHVNV-UHFFFAOYSA-N 4-(4-phenylmethoxyphenoxy)phthalic acid Chemical compound C1=C(C(O)=O)C(C(=O)O)=CC=C1OC(C=C1)=CC=C1OCC1=CC=CC=C1 AQHKULBPGOHVNV-UHFFFAOYSA-N 0.000 description 2
- FQPRUMXSHZSJGM-WEVVVXLNSA-N 4-[(E)-N-hydroxy-C-methylcarbonimidoyl]benzene-1,3-diol Chemical compound C\C(=N/O)C1=C(O)C=C(O)C=C1 FQPRUMXSHZSJGM-WEVVVXLNSA-N 0.000 description 2
- RHMPLDJJXGPMEX-UHFFFAOYSA-N 4-fluorophenol Chemical compound OC1=CC=C(F)C=C1 RHMPLDJJXGPMEX-UHFFFAOYSA-N 0.000 description 2
- IHSKKLNGJVDOMP-UHFFFAOYSA-N 5-benzyl-3h-2-benzofuran-1-one Chemical compound C=1C=C2C(=O)OCC2=CC=1CC1=CC=CC=C1 IHSKKLNGJVDOMP-UHFFFAOYSA-N 0.000 description 2
- CIRRFAQIWQFQSS-UHFFFAOYSA-N 6-ethyl-o-cresol Chemical compound CCC1=CC=CC(C)=C1O CIRRFAQIWQFQSS-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- 206010053138 Congenital aplastic anaemia Diseases 0.000 description 2
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 241000255601 Drosophila melanogaster Species 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 101710111663 Egl nine homolog 1 Proteins 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 208000036696 Microcytic anaemia Diseases 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- UBQYURCVBFRUQT-UHFFFAOYSA-N N-benzoyl-Ferrioxamine B Chemical compound CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN UBQYURCVBFRUQT-UHFFFAOYSA-N 0.000 description 2
- 150000001204 N-oxides Chemical class 0.000 description 2
- 238000010934 O-alkylation reaction Methods 0.000 description 2
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 108010050808 Procollagen Proteins 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 206010063837 Reperfusion injury Diseases 0.000 description 2
- 241000580858 Simian-Human immunodeficiency virus Species 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 206010043391 Thalassaemia beta Diseases 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 208000025865 Ulcer Diseases 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 208000022440 X-linked sideroblastic anemia 1 Diseases 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
- 125000004423 acyloxy group Chemical group 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 125000003275 alpha amino acid group Chemical group 0.000 description 2
- HWXBTNAVRSUOJR-UHFFFAOYSA-N alpha-hydroxyglutaric acid Natural products OC(=O)C(O)CCC(O)=O HWXBTNAVRSUOJR-UHFFFAOYSA-N 0.000 description 2
- 229940009533 alpha-ketoglutaric acid Drugs 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- RUFVCXBLAPWBAY-UHFFFAOYSA-N butyl 1-bromo-4-hydroxy-6-methoxyisoquinoline-3-carboxylate Chemical compound C1=CC(OC)=CC2=C(O)C(C(=O)OCCCC)=NC(Br)=C21 RUFVCXBLAPWBAY-UHFFFAOYSA-N 0.000 description 2
- XGJVLDIEWZFABL-UHFFFAOYSA-N butyl 1-cyano-4-hydroxy-6-(4-methoxyphenoxy)isoquinoline-3-carboxylate Chemical compound C=1C2=C(O)C(C(=O)OCCCC)=NC(C#N)=C2C=CC=1OC1=CC=C(OC)C=C1 XGJVLDIEWZFABL-UHFFFAOYSA-N 0.000 description 2
- GLWOJHYXQICMGL-UHFFFAOYSA-N butyl 1-cyano-4-hydroxy-6-[(2-methyl-1,3-benzoxazol-6-yl)oxy]isoquinoline-3-carboxylate Chemical compound C1=C2N=C(C)OC2=CC(OC=2C=CC3=C(C#N)N=C(C(=C3C=2)O)C(=O)OCCCC)=C1 GLWOJHYXQICMGL-UHFFFAOYSA-N 0.000 description 2
- SUDXTEYJDZIWKJ-UHFFFAOYSA-N butyl 1-cyano-6-[[2-(dimethylamino)-1,3-benzoxazol-5-yl]oxy]-4-hydroxyisoquinoline-3-carboxylate Chemical compound C1=C2OC(N(C)C)=NC2=CC(OC=2C=CC3=C(C#N)N=C(C(=C3C=2)O)C(=O)OCCCC)=C1 SUDXTEYJDZIWKJ-UHFFFAOYSA-N 0.000 description 2
- DDHTXCWYYNYMKM-UHFFFAOYSA-N butyl 1-cyano-7-(2,6-dimethylphenoxy)-4-hydroxyisoquinoline-3-carboxylate Chemical compound C1=CC2=C(O)C(C(=O)OCCCC)=NC(C#N)=C2C=C1OC1=C(C)C=CC=C1C DDHTXCWYYNYMKM-UHFFFAOYSA-N 0.000 description 2
- XRIPLRAIFKMRPI-UHFFFAOYSA-N butyl 6-(1,3-benzodioxol-5-yloxy)-1-cyano-4-hydroxyisoquinoline-3-carboxylate Chemical class C1=C2OCOC2=CC(OC=2C=CC3=C(C#N)N=C(C(=C3C=2)O)C(=O)OCCCC)=C1 XRIPLRAIFKMRPI-UHFFFAOYSA-N 0.000 description 2
- SUPZBHWMQJCJHW-UHFFFAOYSA-N butyl 6-(4-chloro-2,6-dimethylphenoxy)-1-cyano-4-hydroxyisoquinoline-3-carboxylate Chemical compound C=1C2=C(O)C(C(=O)OCCCC)=NC(C#N)=C2C=CC=1OC1=C(C)C=C(Cl)C=C1C SUPZBHWMQJCJHW-UHFFFAOYSA-N 0.000 description 2
- UZAAJWYRGUGIFS-UHFFFAOYSA-N butyl 7-(1,3-benzodioxol-5-yloxy)-1-chloro-4-hydroxyisoquinoline-3-carboxylate Chemical class C1=C2OCOC2=CC(OC2=CC3=C(Cl)N=C(C(=C3C=C2)O)C(=O)OCCCC)=C1 UZAAJWYRGUGIFS-UHFFFAOYSA-N 0.000 description 2
- ITZYCNSDVPZMRL-UHFFFAOYSA-N butyl 7-(1,3-benzodioxol-5-yloxy)-4-hydroxy-1-oxo-2h-isoquinoline-3-carboxylate Chemical compound C1=C2OCOC2=CC(OC=2C=C3C(=O)NC(=C(C3=CC=2)O)C(=O)OCCCC)=C1 ITZYCNSDVPZMRL-UHFFFAOYSA-N 0.000 description 2
- WRPOWOJZYAGJAH-UHFFFAOYSA-N butyl 7-(2,3-dihydro-1-benzofuran-5-yloxy)-4-hydroxy-1-oxo-2h-isoquinoline-3-carboxylate Chemical compound C1=C2OCCC2=CC(OC=2C=C3C(=O)NC(=C(C3=CC=2)O)C(=O)OCCCC)=C1 WRPOWOJZYAGJAH-UHFFFAOYSA-N 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 150000003857 carboxamides Chemical class 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 2
- 238000007333 cyanation reaction Methods 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 229960000958 deferoxamine Drugs 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- RWRIWBAIICGTTQ-UHFFFAOYSA-N difluoromethane Chemical compound FCF RWRIWBAIICGTTQ-UHFFFAOYSA-N 0.000 description 2
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 239000012039 electrophile Substances 0.000 description 2
- 206010015037 epilepsy Diseases 0.000 description 2
- NIEDEHWURUFCAK-UHFFFAOYSA-N ethyl 1-bromo-4-hydroxy-7-phenylmethoxyisoquinoline-3-carboxylate Chemical compound C1=CC2=C(O)C(C(=O)OCC)=NC(Br)=C2C=C1OCC1=CC=CC=C1 NIEDEHWURUFCAK-UHFFFAOYSA-N 0.000 description 2
- MWOXREDQAMQMHE-UHFFFAOYSA-N ethyl 1-cyano-4,7-dihydroxyisoquinoline-3-carboxylate Chemical compound C1=C(O)C=CC2=C(O)C(C(=O)OCC)=NC(C#N)=C21 MWOXREDQAMQMHE-UHFFFAOYSA-N 0.000 description 2
- YWXUNEVKOCEMRO-UHFFFAOYSA-N ethyl 2-(5-nitro-1,3-dioxoisoindol-2-yl)acetate Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(CC(=O)OCC)C(=O)C2=C1 YWXUNEVKOCEMRO-UHFFFAOYSA-N 0.000 description 2
- ZSERBANGERUKNH-UHFFFAOYSA-N ethyl 2-[5-[(2-methyl-1,3-benzothiazol-6-yl)oxy]-1,3-dioxoisoindol-2-yl]acetate Chemical compound C1=C2N=C(C)SC2=CC(OC2=CC=C3C(=O)N(C(C3=C2)=O)CC(=O)OCC)=C1 ZSERBANGERUKNH-UHFFFAOYSA-N 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000010685 fatty oil Substances 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 230000033444 hydroxylation Effects 0.000 description 2
- 238000005805 hydroxylation reaction Methods 0.000 description 2
- 208000006278 hypochromic anemia Diseases 0.000 description 2
- 230000001146 hypoxic effect Effects 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 239000003999 initiator Substances 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 150000002537 isoquinolines Chemical class 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- QQNREUPBHNWQAJ-UHFFFAOYSA-N methyl 1-cyano-4-hydroxy-8-(2-methoxyphenoxy)isoquinoline-3-carboxylate Chemical compound C=1C=CC2=C(O)C(C(=O)OC)=NC(C#N)=C2C=1OC1=CC=CC=C1OC QQNREUPBHNWQAJ-UHFFFAOYSA-N 0.000 description 2
- FMMJCZAVXXUHGS-UHFFFAOYSA-N methyl 1-cyano-4-methoxy-8-phenoxyisoquinoline-3-carboxylate Chemical compound C=1C=CC2=C(OC)C(C(=O)OC)=NC(C#N)=C2C=1OC1=CC=CC=C1 FMMJCZAVXXUHGS-UHFFFAOYSA-N 0.000 description 2
- MOFSZTIGSWETBS-UHFFFAOYSA-N methyl 2-(4-fluorophenoxy)-6-methylbenzoate Chemical compound COC(=O)C1=C(C)C=CC=C1OC1=CC=C(F)C=C1 MOFSZTIGSWETBS-UHFFFAOYSA-N 0.000 description 2
- GYQBPYXMRNEAKZ-UHFFFAOYSA-N methyl 2-[(4-methylphenyl)sulfonylamino]acetate Chemical compound COC(=O)CNS(=O)(=O)C1=CC=C(C)C=C1 GYQBPYXMRNEAKZ-UHFFFAOYSA-N 0.000 description 2
- PWVVZEWUVXUWPV-UHFFFAOYSA-N methyl 2-methyl-6-phenoxybenzoate Chemical compound COC(=O)C1=C(C)C=CC=C1OC1=CC=CC=C1 PWVVZEWUVXUWPV-UHFFFAOYSA-N 0.000 description 2
- IPPPZCXGKFWQEC-UHFFFAOYSA-N methyl 3-iodo-2-methylbenzoate Chemical compound COC(=O)C1=CC=CC(I)=C1C IPPPZCXGKFWQEC-UHFFFAOYSA-N 0.000 description 2
- GMCNQYGTPVDGFO-UHFFFAOYSA-N methyl 4-hydroxy-5-phenoxyisoquinoline-3-carboxylate Chemical compound C12=C(O)C(C(=O)OC)=NC=C2C=CC=C1OC1=CC=CC=C1 GMCNQYGTPVDGFO-UHFFFAOYSA-N 0.000 description 2
- CYPUOPDGJUONAD-UHFFFAOYSA-N methyl 7-benzyl-4-hydroxyisoquinoline-3-carboxylate Chemical compound C1=CC2=C(O)C(C(=O)OC)=NC=C2C=C1CC1=CC=CC=C1 CYPUOPDGJUONAD-UHFFFAOYSA-N 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- 150000004682 monohydrates Chemical class 0.000 description 2
- 208000031225 myocardial ischemia Diseases 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluic acid Chemical compound CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 244000045947 parasite Species 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthridine Chemical compound C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 2
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 239000004014 plasticizer Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 229940069328 povidone Drugs 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 208000031162 sideroblastic anemia Diseases 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 2
- 229940001584 sodium metabisulfite Drugs 0.000 description 2
- 235000010262 sodium metabisulphite Nutrition 0.000 description 2
- NESLWCLHZZISNB-UHFFFAOYSA-M sodium phenolate Chemical class [Na+].[O-]C1=CC=CC=C1 NESLWCLHZZISNB-UHFFFAOYSA-M 0.000 description 2
- 239000008109 sodium starch glycolate Substances 0.000 description 2
- 229920003109 sodium starch glycolate Polymers 0.000 description 2
- 229940079832 sodium starch glycolate Drugs 0.000 description 2
- 239000007901 soft capsule Substances 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 2
- 125000000464 thioxo group Chemical group S=* 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 2
- 231100000397 ulcer Toxicity 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 229920001285 xanthan gum Polymers 0.000 description 2
- 235000010493 xanthan gum Nutrition 0.000 description 2
- 239000000230 xanthan gum Substances 0.000 description 2
- 229940082509 xanthan gum Drugs 0.000 description 2
- WRSWIWOVJBYZAW-UHFFFAOYSA-M zinc;methanidylbenzene;bromide Chemical compound Br[Zn+].[CH2-]C1=CC=CC=C1 WRSWIWOVJBYZAW-UHFFFAOYSA-M 0.000 description 2
- TXTWXQXDMWILOF-UHFFFAOYSA-N (2-ethoxy-2-oxoethyl)azanium;chloride Chemical compound [Cl-].CCOC(=O)C[NH3+] TXTWXQXDMWILOF-UHFFFAOYSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- OINOLIGLRWFXAH-NSHDSACASA-N (2s)-2-[(1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carbonyl)amino]propanoic acid Chemical compound C1=CC2=C(O)C(C(=O)N[C@@H](C)C(O)=O)=NC(C#N)=C2C=C1OC1=CC=CC=C1 OINOLIGLRWFXAH-NSHDSACASA-N 0.000 description 1
- HEEJNIOLTLADLS-NSHDSACASA-N (2s)-2-[(1-cyano-4-hydroxy-8-phenoxyisoquinoline-3-carbonyl)amino]propanoic acid Chemical compound C=1C=CC2=C(O)C(C(=O)N[C@@H](C)C(O)=O)=NC(C#N)=C2C=1OC1=CC=CC=C1 HEEJNIOLTLADLS-NSHDSACASA-N 0.000 description 1
- DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-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
- CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 1
- IQKPRBSODYLOSB-UHFFFAOYSA-N 1-cyano-6-(2,3-dihydro-1-benzofuran-5-yloxy)-4-hydroxyisoquinoline-3-carboxylic acid Chemical compound C(#N)C1=NC(=C(C2=CC(=CC=C12)OC=1C=CC2=C(CCO2)C=1)O)C(=O)O IQKPRBSODYLOSB-UHFFFAOYSA-N 0.000 description 1
- CAVIJJPKFLREIZ-UHFFFAOYSA-N 1-cyano-6-(2-ethyl-6-methylphenoxy)-4-hydroxyisoquinoline-3-carboxylic acid Chemical compound C(#N)C1=NC(=C(C2=CC(=CC=C12)OC1=C(C=CC=C1C)CC)O)C(=O)O CAVIJJPKFLREIZ-UHFFFAOYSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- FDDBUIWRNBGXHB-UHFFFAOYSA-N 1-iodoisoquinoline Chemical compound C1=CC=C2C(I)=NC=CC2=C1 FDDBUIWRNBGXHB-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- KYWCUACNBIYDNL-UHFFFAOYSA-N 1-oxo-2h-isoquinoline-3-carboxylic acid Chemical compound C1=CC=C2C(=O)NC(C(=O)O)=CC2=C1 KYWCUACNBIYDNL-UHFFFAOYSA-N 0.000 description 1
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
- TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 1
- JYYBMURWNLITAF-UHFFFAOYSA-N 2,2-dibenzylcyclotridecan-1-one Chemical compound C(C1=CC=CC=C1)C1(C(CCCCCCCCCCC1)=O)CC1=CC=CC=C1 JYYBMURWNLITAF-UHFFFAOYSA-N 0.000 description 1
- JNYKOGUXPNAUIB-UHFFFAOYSA-N 2,3-dihydro-1-benzofuran-5-ol Chemical compound OC1=CC=C2OCCC2=C1 JNYKOGUXPNAUIB-UHFFFAOYSA-N 0.000 description 1
- VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 1
- BPRYUXCVCCNUFE-UHFFFAOYSA-N 2,4,6-trimethylphenol Chemical compound CC1=CC(C)=C(O)C(C)=C1 BPRYUXCVCCNUFE-UHFFFAOYSA-N 0.000 description 1
- OLKHXIWCDITTRS-UHFFFAOYSA-N 2-[(1-chloro-4-hydroxy-5-phenylisoquinoline-3-carbonyl)amino]acetic acid Chemical compound C12=C(O)C(C(=O)NCC(=O)O)=NC(Cl)=C2C=CC=C1C1=CC=CC=C1 OLKHXIWCDITTRS-UHFFFAOYSA-N 0.000 description 1
- UZPXOYMIEKORSO-UHFFFAOYSA-N 2-[(1-chloro-4-hydroxy-6-propan-2-yloxyisoquinoline-3-carbonyl)amino]acetic acid Chemical compound ClC1=NC(C(=O)NCC(O)=O)=C(O)C2=CC(OC(C)C)=CC=C21 UZPXOYMIEKORSO-UHFFFAOYSA-N 0.000 description 1
- HNKNRBCTSVOMTO-UHFFFAOYSA-N 2-[(1-chloro-4-hydroxy-8-phenylisoquinoline-3-carbonyl)amino]acetic acid Chemical compound C=1C=CC2=C(O)C(C(=O)NCC(=O)O)=NC(Cl)=C2C=1C1=CC=CC=C1 HNKNRBCTSVOMTO-UHFFFAOYSA-N 0.000 description 1
- KAYGKLVVYZWVAG-UHFFFAOYSA-N 2-[(1-cyano-4-hydroxy-5-phenoxyisoquinoline-3-carbonyl)amino]acetic acid Chemical compound C12=C(O)C(C(=O)NCC(=O)O)=NC(C#N)=C2C=CC=C1OC1=CC=CC=C1 KAYGKLVVYZWVAG-UHFFFAOYSA-N 0.000 description 1
- FBIUHFAZXZTKLZ-UHFFFAOYSA-N 2-[(1-cyano-4-hydroxy-6,7-diphenoxyisoquinoline-3-carbonyl)amino]acetic acid Chemical compound C=1C=CC=CC=1OC1=CC2=C(O)C(C(=O)NCC(=O)O)=NC(C#N)=C2C=C1OC1=CC=CC=C1 FBIUHFAZXZTKLZ-UHFFFAOYSA-N 0.000 description 1
- HKXSOFOZSVJRHD-UHFFFAOYSA-N 2-[(1-cyano-4-hydroxy-6-phenoxyisoquinoline-3-carbonyl)amino]acetic acid Chemical compound C=1C2=C(O)C(C(=O)NCC(=O)O)=NC(C#N)=C2C=CC=1OC1=CC=CC=C1 HKXSOFOZSVJRHD-UHFFFAOYSA-N 0.000 description 1
- DHYMCJJAMYRROZ-UHFFFAOYSA-N 2-[(1-cyano-4-hydroxy-6-phenylsulfanylisoquinoline-3-carbonyl)amino]acetic acid Chemical compound C=1C2=C(O)C(C(=O)NCC(=O)O)=NC(C#N)=C2C=CC=1SC1=CC=CC=C1 DHYMCJJAMYRROZ-UHFFFAOYSA-N 0.000 description 1
- RGUITKKPHCEUJB-UHFFFAOYSA-N 2-[(1-cyano-4-hydroxy-6-propan-2-yloxyisoquinoline-3-carbonyl)amino]acetic acid Chemical compound N#CC1=NC(C(=O)NCC(O)=O)=C(O)C2=CC(OC(C)C)=CC=C21 RGUITKKPHCEUJB-UHFFFAOYSA-N 0.000 description 1
- NLWWCMRQWOUKFR-UHFFFAOYSA-N 2-[(1-cyano-4-hydroxy-7-phenylsulfanylisoquinoline-3-carbonyl)amino]acetic acid Chemical compound C1=CC2=C(O)C(C(=O)NCC(=O)O)=NC(C#N)=C2C=C1SC1=CC=CC=C1 NLWWCMRQWOUKFR-UHFFFAOYSA-N 0.000 description 1
- BJAJGXRKYCBVJL-UHFFFAOYSA-N 2-[(1-cyano-4-hydroxyisoquinoline-3-carbonyl)amino]acetic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)NCC(=O)O)=NC(C#N)=C21 BJAJGXRKYCBVJL-UHFFFAOYSA-N 0.000 description 1
- KWUMPJUJWPWEIN-UHFFFAOYSA-N 2-[(7-butoxy-1-chloro-4-hydroxyisoquinoline-3-carbonyl)amino]acetic acid Chemical compound OC1=C(C(=O)NCC(O)=O)N=C(Cl)C2=CC(OCCCC)=CC=C21 KWUMPJUJWPWEIN-UHFFFAOYSA-N 0.000 description 1
- DKJSLSRAJRSGOE-UHFFFAOYSA-N 2-[(7-butoxy-1-cyano-4-hydroxyisoquinoline-3-carbonyl)amino]acetic acid Chemical compound OC1=C(C(=O)NCC(O)=O)N=C(C#N)C2=CC(OCCCC)=CC=C21 DKJSLSRAJRSGOE-UHFFFAOYSA-N 0.000 description 1
- SDHQACBELYIDMP-UHFFFAOYSA-N 2-[(7-chloro-1-cyano-4-hydroxyisoquinoline-3-carbonyl)amino]acetic acid Chemical compound C1=C(Cl)C=CC2=C(O)C(C(=O)NCC(=O)O)=NC(C#N)=C21 SDHQACBELYIDMP-UHFFFAOYSA-N 0.000 description 1
- WNAANIGUEJSPAC-UHFFFAOYSA-N 2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid;ethyl acetate Chemical compound CCOC(C)=O.OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O WNAANIGUEJSPAC-UHFFFAOYSA-N 0.000 description 1
- LUQYALMIYXCNPR-UHFFFAOYSA-N 2-[5-(4-hydroxyphenoxy)-1,3-dioxoisoindol-2-yl]acetic acid Chemical compound OC1=CC=C(OC=2C=C3C(N(C(C3=CC=2)=O)CC(=O)O)=O)C=C1 LUQYALMIYXCNPR-UHFFFAOYSA-N 0.000 description 1
- JYRMFIRRDIJDFS-UHFFFAOYSA-N 2-[[1-cyano-4-hydroxy-7-(4-methoxyphenoxy)isoquinoline-3-carbonyl]amino]acetic acid Chemical compound C1=CC(OC)=CC=C1OC1=CC=C(C(O)=C(N=C2C#N)C(=O)NCC(O)=O)C2=C1 JYRMFIRRDIJDFS-UHFFFAOYSA-N 0.000 description 1
- NJRNDFUKRCYEFU-UHFFFAOYSA-N 2-[[1-cyano-4-hydroxy-7-(trifluoromethyl)isoquinoline-3-carbonyl]amino]acetic acid Chemical compound C1=C(C(F)(F)F)C=CC2=C(O)C(C(=O)NCC(=O)O)=NC(C#N)=C21 NJRNDFUKRCYEFU-UHFFFAOYSA-N 0.000 description 1
- FZFKWPUQJHCEOO-UHFFFAOYSA-N 2-[[1-cyano-6-[[2-(dimethylamino)-1,3-benzoxazol-5-yl]oxy]-4-hydroxyisoquinoline-3-carbonyl]amino]acetic acid Chemical compound N#CC1=NC(C(=O)NCC(O)=O)=C(O)C2=CC(OC=3C=C4N=C(OC4=CC=3)N(C)C)=CC=C21 FZFKWPUQJHCEOO-UHFFFAOYSA-N 0.000 description 1
- YANPNILRMLHKCS-UHFFFAOYSA-N 2-[[6-(1,3-benzodioxol-5-yloxy)-1-cyano-4-hydroxyisoquinoline-3-carbonyl]amino]acetic acid Chemical compound C1=C2OCOC2=CC(OC=2C=CC3=C(C#N)N=C(C(=C3C=2)O)C(=O)NCC(=O)O)=C1 YANPNILRMLHKCS-UHFFFAOYSA-N 0.000 description 1
- TUADYTFWZPZZTP-UHFFFAOYSA-N 2-amino-4-methoxyphenol Chemical compound COC1=CC=C(O)C(N)=C1 TUADYTFWZPZZTP-UHFFFAOYSA-N 0.000 description 1
- FVUFTABOJFRHSU-UHFFFAOYSA-N 2-chloro-6-methoxy-1,3-benzothiazole Chemical compound COC1=CC=C2N=C(Cl)SC2=C1 FVUFTABOJFRHSU-UHFFFAOYSA-N 0.000 description 1
- HZLCGUXUOFWCCN-UHFFFAOYSA-N 2-hydroxynonadecane-1,2,3-tricarboxylic acid Chemical compound CCCCCCCCCCCCCCCCC(C(O)=O)C(O)(C(O)=O)CC(O)=O HZLCGUXUOFWCCN-UHFFFAOYSA-N 0.000 description 1
- RZKJWYDRDBVDJJ-UHFFFAOYSA-N 2-methyl-1,3-benzoxazol-6-ol Chemical compound C1=C(O)C=C2OC(C)=NC2=C1 RZKJWYDRDBVDJJ-UHFFFAOYSA-N 0.000 description 1
- VYWLVEDKNKMRBQ-UHFFFAOYSA-N 2-methyl-6-phenoxybenzoic acid Chemical compound CC1=CC=CC(OC=2C=CC=CC=2)=C1C(O)=O VYWLVEDKNKMRBQ-UHFFFAOYSA-N 0.000 description 1
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- VLRSADZEDXVUPG-UHFFFAOYSA-N 2-naphthalen-1-ylpyridine Chemical compound N1=CC=CC=C1C1=CC=CC2=CC=CC=C12 VLRSADZEDXVUPG-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- CBKDCOKSXCTDAA-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1-benzothiophene Chemical compound C1CCCC2=C1C=CS2 CBKDCOKSXCTDAA-UHFFFAOYSA-N 0.000 description 1
- RQJCIBBOPHNQKB-UHFFFAOYSA-N 4-(1,3-benzodioxol-5-yloxy)benzene-1,2-dicarbonitrile Chemical compound C1=C(C#N)C(C#N)=CC=C1OC1=CC=C(OCO2)C2=C1 RQJCIBBOPHNQKB-UHFFFAOYSA-N 0.000 description 1
- AGNJPVPWVRPJBC-UHFFFAOYSA-N 4-(1,3-benzodioxol-5-yloxy)phthalic acid Chemical compound C1=C(C(O)=O)C(C(=O)O)=CC=C1OC1=CC=C(OCO2)C2=C1 AGNJPVPWVRPJBC-UHFFFAOYSA-N 0.000 description 1
- LWXKLLXAQSUOPR-UHFFFAOYSA-N 4-(2,4,6-trimethylphenoxy)phthalic acid Chemical compound CC1=CC(C)=CC(C)=C1OC1=CC=C(C(O)=O)C(C(O)=O)=C1 LWXKLLXAQSUOPR-UHFFFAOYSA-N 0.000 description 1
- LJUVUOSWARAIBZ-UHFFFAOYSA-N 4-(2,6-dimethylphenoxy)benzene-1,2-dicarbonitrile Chemical compound CC1=CC=CC(C)=C1OC1=CC=C(C#N)C(C#N)=C1 LJUVUOSWARAIBZ-UHFFFAOYSA-N 0.000 description 1
- MZCBUZDIEROHTQ-UHFFFAOYSA-N 4-(2,6-dimethylphenoxy)phthalic acid Chemical compound CC1=CC=CC(C)=C1OC1=CC=C(C(O)=O)C(C(O)=O)=C1 MZCBUZDIEROHTQ-UHFFFAOYSA-N 0.000 description 1
- NQJLTUXAJWYIBU-UHFFFAOYSA-N 4-(2-ethyl-6-methylphenoxy)phthalic acid Chemical compound CCC1=CC=CC(C)=C1OC1=CC=C(C(O)=O)C(C(O)=O)=C1 NQJLTUXAJWYIBU-UHFFFAOYSA-N 0.000 description 1
- XOXZLHMCZVDPMJ-UHFFFAOYSA-N 4-(4-chloro-2,6-dimethylphenoxy)benzene-1,2-dicarbonitrile Chemical compound CC1=CC(Cl)=CC(C)=C1OC1=CC=C(C#N)C(C#N)=C1 XOXZLHMCZVDPMJ-UHFFFAOYSA-N 0.000 description 1
- FMQTYYQXRCGUSY-UHFFFAOYSA-N 4-(4-chloro-2,6-dimethylphenoxy)phthalic acid Chemical compound CC1=CC(Cl)=CC(C)=C1OC1=CC=C(C(O)=O)C(C(O)=O)=C1 FMQTYYQXRCGUSY-UHFFFAOYSA-N 0.000 description 1
- AHIFENNSJHJWRX-UHFFFAOYSA-N 4-(6-ethoxy-1,3-benzothiazol-2-yl)morpholine Chemical compound S1C2=CC(OCC)=CC=C2N=C1N1CCOCC1 AHIFENNSJHJWRX-UHFFFAOYSA-N 0.000 description 1
- 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 1
- PVNDKZORTQTUNA-UHFFFAOYSA-N 4-hydroxy-7-phenoxyisoquinoline-3-carboxylic acid Chemical compound OC1=C(N=CC2=CC(=CC=C12)OC1=CC=CC=C1)C(=O)O PVNDKZORTQTUNA-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-M 4-hydroxybenzoate Chemical compound OC1=CC=C(C([O-])=O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-M 0.000 description 1
- SDANCITUOADILO-UHFFFAOYSA-N 4-hydroxyisoquinoline-3-carboxylic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=NC=C21 SDANCITUOADILO-UHFFFAOYSA-N 0.000 description 1
- YBUGOACXDPDUIR-UHFFFAOYSA-N 4-methoxy-2-nitrophenol Chemical compound COC1=CC=C(O)C([N+]([O-])=O)=C1 YBUGOACXDPDUIR-UHFFFAOYSA-N 0.000 description 1
- 102100033051 40S ribosomal protein S19 Human genes 0.000 description 1
- GDRVFDDBLLKWRI-UHFFFAOYSA-N 4H-quinolizine Chemical compound C1=CC=CN2CC=CC=C21 GDRVFDDBLLKWRI-UHFFFAOYSA-N 0.000 description 1
- IUSPXLCLQIZFHL-UHFFFAOYSA-N 5-bromo-3h-2-benzofuran-1-one Chemical compound BrC1=CC=C2C(=O)OCC2=C1 IUSPXLCLQIZFHL-UHFFFAOYSA-N 0.000 description 1
- DSBRFLKNUPGGHJ-UHFFFAOYSA-N 5-ethoxy-3H-1,3-benzoxazole-2-thione Chemical compound C(C)OC=1C=CC2=C(N=C(O2)S)C1 DSBRFLKNUPGGHJ-UHFFFAOYSA-N 0.000 description 1
- QGTUVLRFJOUWBN-UHFFFAOYSA-N 5-methoxy-3h-1,3-benzoxazole-2-thione Chemical compound COC1=CC=C2OC(=S)NC2=C1 QGTUVLRFJOUWBN-UHFFFAOYSA-N 0.000 description 1
- XTJBODKPJOJNOZ-UHFFFAOYSA-N 5-methoxy-n,n-dimethyl-1,3-benzoxazol-2-amine Chemical compound COC1=CC=C2OC(N(C)C)=NC2=C1 XTJBODKPJOJNOZ-UHFFFAOYSA-N 0.000 description 1
- KZHGPDSVHSDCMX-UHFFFAOYSA-N 6-methoxy-1,3-benzothiazol-2-amine Chemical compound COC1=CC=C2N=C(N)SC2=C1 KZHGPDSVHSDCMX-UHFFFAOYSA-N 0.000 description 1
- DYHLJSUORLPGNT-UHFFFAOYSA-N 6-methoxy-2-methyl-1,3-benzothiazole Chemical compound COC1=CC=C2N=C(C)SC2=C1 DYHLJSUORLPGNT-UHFFFAOYSA-N 0.000 description 1
- VMQRPQVONACOIO-UHFFFAOYSA-N 7-(1,3-benzodioxol-5-yloxy)-4-hydroxy-1-oxo-2H-isoquinoline-3-carboxylic acid Chemical compound O1COC2=C1C=CC(=C2)OC1=CC=C2C(=C(NC(C2=C1)=O)C(=O)O)O VMQRPQVONACOIO-UHFFFAOYSA-N 0.000 description 1
- YEGDFLRSMYSBQW-UHFFFAOYSA-N 7-[[2-(dimethylamino)-1,3-benzoxazol-5-yl]oxy]-4-hydroxy-1-oxo-2H-isoquinoline-3-carboxylic acid Chemical compound CN(C=1OC2=C(N1)C=C(C=C2)OC2=CC=C1C(=C(N=C(C1=C2)O)C(=O)O)O)C YEGDFLRSMYSBQW-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 108010044267 Abnormal Hemoglobins Proteins 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000030090 Acute Disease Diseases 0.000 description 1
- 208000009304 Acute Kidney Injury Diseases 0.000 description 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 208000032671 Allergic granulomatous angiitis Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 200000000007 Arterial disease Diseases 0.000 description 1
- 108090000448 Aryl Hydrocarbon Receptors Proteins 0.000 description 1
- 102100026792 Aryl hydrocarbon receptor Human genes 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 208000037157 Azotemia Diseases 0.000 description 1
- 102000018720 Basic Helix-Loop-Helix Transcription Factors Human genes 0.000 description 1
- 108010027344 Basic Helix-Loop-Helix Transcription Factors Proteins 0.000 description 1
- 208000033932 Blackfan-Diamond anemia Diseases 0.000 description 1
- 208000018240 Bone Marrow Failure disease Diseases 0.000 description 1
- 206010065553 Bone marrow failure Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- MAVCZMURIGNIQK-UHFFFAOYSA-N BrC1=NC(=C(C2=CC(=CC=C12)OC1=C(C=CC=C1C)C)O)C(=O)O Chemical compound BrC1=NC(=C(C2=CC(=CC=C12)OC1=C(C=CC=C1C)C)O)C(=O)O MAVCZMURIGNIQK-UHFFFAOYSA-N 0.000 description 1
- VIUZXVFHHXAMIR-UHFFFAOYSA-N C(#N)C1=NC(=C(C2=CC(=CC=C12)OC1=CC=CC=C1)O)C(=O)O Chemical compound C(#N)C1=NC(=C(C2=CC(=CC=C12)OC1=CC=CC=C1)O)C(=O)O VIUZXVFHHXAMIR-UHFFFAOYSA-N 0.000 description 1
- UUMAWMZRBDOJJZ-WUSPCOQVSA-N C(#N)C1=NC(=C(C2=CC=CC(=C12)OC1=CC=CC=C1)O)C(=O)N[C@H](C(=O)O)C.C(#N)C1=NC(=C(C2=CC=CC(=C12)OC1=CC=CC=C1)OC)C(=O)NCC(=O)O Chemical compound C(#N)C1=NC(=C(C2=CC=CC(=C12)OC1=CC=CC=C1)O)C(=O)N[C@H](C(=O)O)C.C(#N)C1=NC(=C(C2=CC=CC(=C12)OC1=CC=CC=C1)OC)C(=O)NCC(=O)O UUMAWMZRBDOJJZ-WUSPCOQVSA-N 0.000 description 1
- DTAJSQZDWVYSIC-UHFFFAOYSA-N COC1=CC=C(OC2=CC=C3C(=C(N=C(C3=C2)O)C(=O)O)O)C=C1 Chemical compound COC1=CC=C(OC2=CC=C3C(=C(N=C(C3=C2)O)C(=O)O)O)C=C1 DTAJSQZDWVYSIC-UHFFFAOYSA-N 0.000 description 1
- 101100011377 Caenorhabditis elegans egl-9 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 206010007558 Cardiac failure chronic Diseases 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 102100035882 Catalase Human genes 0.000 description 1
- 108010053835 Catalase Proteins 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- 241000206575 Chondrus crispus Species 0.000 description 1
- 208000006344 Churg-Strauss Syndrome Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229910021592 Copper(II) chloride Inorganic materials 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 108010019673 Darbepoetin alfa Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 201000004449 Diamond-Blackfan anemia Diseases 0.000 description 1
- PYGXAGIECVVIOZ-UHFFFAOYSA-N Dibutyl decanedioate Chemical compound CCCCOC(=O)CCCCCCCCC(=O)OCCCC PYGXAGIECVVIOZ-UHFFFAOYSA-N 0.000 description 1
- 108010028143 Dioxygenases Proteins 0.000 description 1
- 102000016680 Dioxygenases Human genes 0.000 description 1
- 101000595915 Drosophila melanogaster Procollagen-lysine,2-oxoglutarate 5-dioxygenase Proteins 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 208000018428 Eosinophilic granulomatosis with polyangiitis Diseases 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 201000004939 Fanconi anemia Diseases 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 208000028387 Felty syndrome Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 238000005590 Gabriel-Colman reaction Methods 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 108091052347 Glucose transporter family Proteins 0.000 description 1
- 102000042092 Glucose transporter family Human genes 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 102220498322 HLA class II histocompatibility antigen, DR beta 3 chain_R40S_mutation Human genes 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 1
- 206010019617 Henoch-Schonlein purpura Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 206010056328 Hepatic ischaemia Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 102000004157 Hydrolases Human genes 0.000 description 1
- 108090000604 Hydrolases Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000031814 IgA Vasculitis Diseases 0.000 description 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 241001572354 Lycaena hyllus Species 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 238000006751 Mitsunobu reaction Methods 0.000 description 1
- 101100389118 Mus musculus Egln1 gene Proteins 0.000 description 1
- 101000987583 Mus musculus Eosinophil peroxidase Proteins 0.000 description 1
- 101000920670 Mus musculus Erythropoietin Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
- 238000006411 Negishi coupling reaction Methods 0.000 description 1
- 102000007999 Nuclear Proteins Human genes 0.000 description 1
- 108010089610 Nuclear Proteins Proteins 0.000 description 1
- ADYJYXZFLQPQSX-UHFFFAOYSA-N OC1=NC(=CC2=CC=CC(=C12)OC1=CC=CC=C1)C(=O)O Chemical compound OC1=NC(=CC2=CC=CC(=C12)OC1=CC=CC=C1)C(=O)O ADYJYXZFLQPQSX-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 206010033661 Pancytopenia Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 208000000733 Paroxysmal Hemoglobinuria Diseases 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 101710170720 Prolyl hydroxylase EGLN3 Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 208000003670 Pure Red-Cell Aplasia Diseases 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 101000881681 Rattus norvegicus Prolyl hydroxylase EGLN3 Proteins 0.000 description 1
- 208000003782 Raynaud disease Diseases 0.000 description 1
- 208000012322 Raynaud phenomenon Diseases 0.000 description 1
- 208000033501 Refractory anemia with excess blasts Diseases 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 208000033626 Renal failure acute Diseases 0.000 description 1
- 206010063897 Renal ischaemia Diseases 0.000 description 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 238000003436 Schotten-Baumann reaction Methods 0.000 description 1
- LUSZGTFNYDARNI-UHFFFAOYSA-N Sesamol Chemical compound OC1=CC=C2OCOC2=C1 LUSZGTFNYDARNI-UHFFFAOYSA-N 0.000 description 1
- 201000004283 Shwachman-Diamond syndrome Diseases 0.000 description 1
- 229910003691 SiBr Inorganic materials 0.000 description 1
- 206010040943 Skin Ulcer Diseases 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 201000009594 Systemic Scleroderma Diseases 0.000 description 1
- 206010042953 Systemic sclerosis Diseases 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 206010043561 Thrombocytopenic purpura Diseases 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- QKDLQFSLLCQTOH-UHFFFAOYSA-N Trichodonin Natural products C1C(O)C2C3(COC(=O)C)C(C=O)C(C)(C)CCC3OC(=O)C22C(=O)C(=C)C1C2 QKDLQFSLLCQTOH-UHFFFAOYSA-N 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 102000006275 Ubiquitin-Protein Ligases Human genes 0.000 description 1
- 108010083111 Ubiquitin-Protein Ligases Proteins 0.000 description 1
- 102000053200 Von Hippel-Lindau Tumor Suppressor Human genes 0.000 description 1
- 108700031765 Von Hippel-Lindau Tumor Suppressor Proteins 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 101100450701 Xenopus laevis hif1a gene Proteins 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- LWWVMTBTQNNOBU-UHFFFAOYSA-N [Na].C(CCC)OC(=O)C=1N=C(C2=CC=C(C=C2C1O)OC1=C(C=CC=C1C)C)O Chemical compound [Na].C(CCC)OC(=O)C=1N=C(C2=CC=C(C=C2C1O)OC1=C(C=CC=C1C)C)O LWWVMTBTQNNOBU-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 210000002506 abnormal erythrocyte Anatomy 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 201000011040 acute kidney failure Diseases 0.000 description 1
- 208000012998 acute renal failure Diseases 0.000 description 1
- 206010001053 acute respiratory failure Diseases 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 229940040563 agaric acid Drugs 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 125000005189 alkyl hydroxy group Chemical group 0.000 description 1
- 150000008051 alkyl sulfates Chemical class 0.000 description 1
- 125000005233 alkylalcohol group Chemical group 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 1
- 235000008206 alpha-amino acids Nutrition 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 125000006598 aminocarbonylamino group Chemical group 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 229940115115 aranesp Drugs 0.000 description 1
- 101150024767 arnT gene Proteins 0.000 description 1
- 125000005163 aryl sulfanyl group Chemical group 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- BYBIRLURVZSVME-UHFFFAOYSA-M benzene;copper(1+);trifluoromethanesulfonate Chemical compound [Cu+].C1=CC=CC=C1.[O-]S(=O)(=O)C(F)(F)F BYBIRLURVZSVME-UHFFFAOYSA-M 0.000 description 1
- 150000001556 benzimidazoles Chemical class 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 1
- 208000005980 beta thalassemia Diseases 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- KNSMIUKQMGHLBP-UHFFFAOYSA-N butyl 1-bromo-4-hydroxy-6-(4-propoxyphenoxy)isoquinoline-3-carboxylate Chemical compound C=1C2=C(O)C(C(=O)OCCCC)=NC(Br)=C2C=CC=1OC1=CC=C(OCCC)C=C1 KNSMIUKQMGHLBP-UHFFFAOYSA-N 0.000 description 1
- UQFXVUUMEQWSCN-UHFFFAOYSA-N butyl 1-bromo-4-hydroxy-6-phenoxyisoquinoline-3-carboxylate Chemical compound C=1C2=C(O)C(C(=O)OCCCC)=NC(Br)=C2C=CC=1OC1=CC=CC=C1 UQFXVUUMEQWSCN-UHFFFAOYSA-N 0.000 description 1
- GHWORVKUBOECAQ-UHFFFAOYSA-N butyl 1-bromo-4-hydroxy-7-(4-methoxyphenoxy)isoquinoline-3-carboxylate Chemical compound C1=CC2=C(O)C(C(=O)OCCCC)=NC(Br)=C2C=C1OC1=CC=C(OC)C=C1 GHWORVKUBOECAQ-UHFFFAOYSA-N 0.000 description 1
- BMZXICMMXHKSOV-UHFFFAOYSA-N butyl 1-bromo-4-hydroxy-7-(trifluoromethyl)isoquinoline-3-carboxylate Chemical compound C1=C(C(F)(F)F)C=CC2=C(O)C(C(=O)OCCCC)=NC(Br)=C21 BMZXICMMXHKSOV-UHFFFAOYSA-N 0.000 description 1
- NUHJKMMKYAEVFL-UHFFFAOYSA-N butyl 1-bromo-6-(2,3-dihydro-1-benzofuran-5-yloxy)-4-hydroxyisoquinoline-3-carboxylate Chemical compound C1=C2OCCC2=CC(OC=2C=CC3=C(Br)N=C(C(=C3C=2)O)C(=O)OCCCC)=C1 NUHJKMMKYAEVFL-UHFFFAOYSA-N 0.000 description 1
- ROAYQANCNYWGER-UHFFFAOYSA-N butyl 1-bromo-6-(2-ethyl-6-methylphenoxy)-4-hydroxyisoquinoline-3-carboxylate Chemical compound C=1C2=C(O)C(C(=O)OCCCC)=NC(Br)=C2C=CC=1OC1=C(C)C=CC=C1CC ROAYQANCNYWGER-UHFFFAOYSA-N 0.000 description 1
- PSJXLPDCVRPZKI-UHFFFAOYSA-N butyl 1-bromo-6-(4-chloro-2,6-dimethylphenoxy)-4-hydroxyisoquinoline-3-carboxylate Chemical compound C=1C2=C(O)C(C(=O)OCCCC)=NC(Br)=C2C=CC=1OC1=C(C)C=C(Cl)C=C1C PSJXLPDCVRPZKI-UHFFFAOYSA-N 0.000 description 1
- HEBJDQOCTKUVDU-UHFFFAOYSA-N butyl 1-bromo-6-chloro-4-hydroxyisoquinoline-3-carboxylate Chemical compound C1=CC(Cl)=CC2=C(O)C(C(=O)OCCCC)=NC(Br)=C21 HEBJDQOCTKUVDU-UHFFFAOYSA-N 0.000 description 1
- YECCBCHRWUQBNT-UHFFFAOYSA-N butyl 1-bromo-6-cyclohexyloxy-4-hydroxyisoquinoline-3-carboxylate Chemical compound C=1C2=C(O)C(C(=O)OCCCC)=NC(Br)=C2C=CC=1OC1CCCCC1 YECCBCHRWUQBNT-UHFFFAOYSA-N 0.000 description 1
- BTSDZERLRRHHOH-UHFFFAOYSA-N butyl 1-bromo-7-(2,6-dimethylphenoxy)-4-hydroxyisoquinoline-3-carboxylate Chemical compound C1=CC2=C(O)C(C(=O)OCCCC)=NC(Br)=C2C=C1OC1=C(C)C=CC=C1C BTSDZERLRRHHOH-UHFFFAOYSA-N 0.000 description 1
- REDDSEWXZQJWCP-UHFFFAOYSA-N butyl 1-bromo-7-(4-fluorophenoxy)-4-hydroxyisoquinoline-3-carboxylate Chemical compound C1=CC2=C(O)C(C(=O)OCCCC)=NC(Br)=C2C=C1OC1=CC=C(F)C=C1 REDDSEWXZQJWCP-UHFFFAOYSA-N 0.000 description 1
- ASBHHVCORSLORK-UHFFFAOYSA-N butyl 1-bromo-7-chloro-4-hydroxyisoquinoline-3-carboxylate Chemical compound C1=C(Cl)C=CC2=C(O)C(C(=O)OCCCC)=NC(Br)=C21 ASBHHVCORSLORK-UHFFFAOYSA-N 0.000 description 1
- YQJUYIBHVZDIBY-UHFFFAOYSA-N butyl 1-chloro-4-hydroxy-6-[(2-methyl-1,3-benzothiazol-6-yl)oxy]isoquinoline-3-carboxylate Chemical compound C1=C2N=C(C)SC2=CC(OC=2C=CC3=C(Cl)N=C(C(=C3C=2)O)C(=O)OCCCC)=C1 YQJUYIBHVZDIBY-UHFFFAOYSA-N 0.000 description 1
- BXIVREXUISPWKL-UHFFFAOYSA-N butyl 1-chloro-4-hydroxy-6-[(2-methyl-1,3-benzoxazol-6-yl)oxy]isoquinoline-3-carboxylate Chemical compound C1=C2N=C(C)OC2=CC(OC=2C=CC3=C(Cl)N=C(C(=C3C=2)O)C(=O)OCCCC)=C1 BXIVREXUISPWKL-UHFFFAOYSA-N 0.000 description 1
- JFWOZBWMNSODHJ-UHFFFAOYSA-N butyl 1-chloro-4-hydroxy-7-(4-methoxyphenoxy)isoquinoline-3-carboxylate Chemical compound C1=CC2=C(O)C(C(=O)OCCCC)=NC(Cl)=C2C=C1OC1=CC=C(OC)C=C1 JFWOZBWMNSODHJ-UHFFFAOYSA-N 0.000 description 1
- BCPRUQZTAUJFQI-UHFFFAOYSA-N butyl 1-chloro-6-[[2-(dimethylamino)-1,3-benzoxazol-5-yl]oxy]-4-hydroxyisoquinoline-3-carboxylate Chemical compound C1=C2OC(N(C)C)=NC2=CC(OC=2C=CC3=C(Cl)N=C(C(=C3C=2)O)C(=O)OCCCC)=C1 BCPRUQZTAUJFQI-UHFFFAOYSA-N 0.000 description 1
- RPUQMNDEUDCUKI-UHFFFAOYSA-N butyl 1-cyano-4-hydroxy-6-(2,4,6-trimethylphenoxy)isoquinoline-3-carboxylate Chemical compound C=1C2=C(O)C(C(=O)OCCCC)=NC(C#N)=C2C=CC=1OC1=C(C)C=C(C)C=C1C RPUQMNDEUDCUKI-UHFFFAOYSA-N 0.000 description 1
- YRRLHMFYUUAKMM-UHFFFAOYSA-N butyl 1-cyano-4-hydroxy-6-(4-propoxyphenoxy)isoquinoline-3-carboxylate Chemical compound C=1C2=C(O)C(C(=O)OCCCC)=NC(C#N)=C2C=CC=1OC1=CC=C(OCCC)C=C1 YRRLHMFYUUAKMM-UHFFFAOYSA-N 0.000 description 1
- XKFVXYYDZHODKV-UHFFFAOYSA-N butyl 1-cyano-4-hydroxy-6-[(2-methyl-1,3-benzothiazol-6-yl)oxy]isoquinoline-3-carboxylate Chemical compound C1=C2N=C(C)SC2=CC(OC=2C=CC3=C(C#N)N=C(C(=C3C=2)O)C(=O)OCCCC)=C1 XKFVXYYDZHODKV-UHFFFAOYSA-N 0.000 description 1
- QXOQXTDTZORARJ-UHFFFAOYSA-N butyl 1-cyano-4-hydroxy-6-[(2-morpholin-4-yl-1,3-benzothiazol-6-yl)oxy]isoquinoline-3-carboxylate Chemical compound C=1C2=C(O)C(C(=O)OCCCC)=NC(C#N)=C2C=CC=1OC(C=C1S2)=CC=C1N=C2N1CCOCC1 QXOQXTDTZORARJ-UHFFFAOYSA-N 0.000 description 1
- ZQUNGZJRMCYOCY-UHFFFAOYSA-N butyl 1-cyano-4-hydroxy-6-methoxyisoquinoline-3-carboxylate Chemical compound C1=CC(OC)=CC2=C(O)C(C(=O)OCCCC)=NC(C#N)=C21 ZQUNGZJRMCYOCY-UHFFFAOYSA-N 0.000 description 1
- IMGANMXTNWFVRF-UHFFFAOYSA-N butyl 1-cyano-4-hydroxy-6-phenylsulfanylisoquinoline-3-carboxylate Chemical compound C=1C2=C(O)C(C(=O)OCCCC)=NC(C#N)=C2C=CC=1SC1=CC=CC=C1 IMGANMXTNWFVRF-UHFFFAOYSA-N 0.000 description 1
- KSDQTQXBYWYRJE-UHFFFAOYSA-N butyl 1-cyano-4-hydroxy-7-(4-methoxyphenoxy)isoquinoline-3-carboxylate Chemical compound C1=CC2=C(O)C(C(=O)OCCCC)=NC(C#N)=C2C=C1OC1=CC=C(OC)C=C1 KSDQTQXBYWYRJE-UHFFFAOYSA-N 0.000 description 1
- XMIFMLZMLFCJGU-UHFFFAOYSA-N butyl 1-cyano-4-hydroxy-7-phenylsulfanylisoquinoline-3-carboxylate Chemical compound C1=CC2=C(O)C(C(=O)OCCCC)=NC(C#N)=C2C=C1SC1=CC=CC=C1 XMIFMLZMLFCJGU-UHFFFAOYSA-N 0.000 description 1
- LESAKNHUTCZMPJ-UHFFFAOYSA-N butyl 1-cyano-4-hydroxyisoquinoline-3-carboxylate Chemical compound C1=CC=CC2=C(O)C(C(=O)OCCCC)=NC(C#N)=C21 LESAKNHUTCZMPJ-UHFFFAOYSA-N 0.000 description 1
- DHMMHIJOLAJOBR-UHFFFAOYSA-N butyl 1-cyano-6-(2,3-dihydro-1-benzofuran-5-yloxy)-4-hydroxyisoquinoline-3-carboxylate Chemical compound C1=C2OCCC2=CC(OC=2C=CC3=C(C#N)N=C(C(=C3C=2)O)C(=O)OCCCC)=C1 DHMMHIJOLAJOBR-UHFFFAOYSA-N 0.000 description 1
- BHMXFKDSEXBMMD-UHFFFAOYSA-N butyl 1-cyano-6-(2,6-dimethylphenoxy)-4-hydroxyisoquinoline-3-carboxylate Chemical compound C=1C2=C(O)C(C(=O)OCCCC)=NC(C#N)=C2C=CC=1OC1=C(C)C=CC=C1C BHMXFKDSEXBMMD-UHFFFAOYSA-N 0.000 description 1
- YPARCWQZLWNPDN-UHFFFAOYSA-N butyl 1-cyano-6-(2-ethyl-6-methylphenoxy)-4-hydroxyisoquinoline-3-carboxylate Chemical compound C=1C2=C(O)C(C(=O)OCCCC)=NC(C#N)=C2C=CC=1OC1=C(C)C=CC=C1CC YPARCWQZLWNPDN-UHFFFAOYSA-N 0.000 description 1
- NUKNXPQQDQXDGH-UHFFFAOYSA-N butyl 1-cyano-7-(4-fluorophenoxy)-4-hydroxyisoquinoline-3-carboxylate Chemical compound C1=CC2=C(O)C(C(=O)OCCCC)=NC(C#N)=C2C=C1OC1=CC=C(F)C=C1 NUKNXPQQDQXDGH-UHFFFAOYSA-N 0.000 description 1
- YBNWMGSPPKMMCV-UHFFFAOYSA-N butyl 1-cyano-7-[[2-(dimethylamino)-1,3-benzoxazol-5-yl]oxy]-4-hydroxyisoquinoline-3-carboxylate Chemical compound C1=C2OC(N(C)C)=NC2=CC(OC2=CC3=C(C#N)N=C(C(=C3C=C2)O)C(=O)OCCCC)=C1 YBNWMGSPPKMMCV-UHFFFAOYSA-N 0.000 description 1
- ZPWHHLDCVYWJJO-UHFFFAOYSA-N butyl 2-aminoacetate;hydron;chloride Chemical class Cl.CCCCOC(=O)CN ZPWHHLDCVYWJJO-UHFFFAOYSA-N 0.000 description 1
- FWAZFHHWGLLYLB-UHFFFAOYSA-N butyl 4-hydroxy-1-oxo-6-(2,4,6-trimethylphenoxy)-2h-isoquinoline-3-carboxylate Chemical compound C=1C2=C(O)C(C(=O)OCCCC)=NC(O)=C2C=CC=1OC1=C(C)C=C(C)C=C1C FWAZFHHWGLLYLB-UHFFFAOYSA-N 0.000 description 1
- AVWWFJJGFLDNFB-UHFFFAOYSA-N butyl 4-hydroxy-6-(4-methoxyphenoxy)isoquinoline-3-carboxylate Chemical compound C=1C2=C(O)C(C(=O)OCCCC)=NC=C2C=CC=1OC1=CC=C(OC)C=C1 AVWWFJJGFLDNFB-UHFFFAOYSA-N 0.000 description 1
- HGEPFEGRRLTDEF-UHFFFAOYSA-N butyl 4-hydroxy-6-[(2-methyl-1,3-benzothiazol-6-yl)oxy]-1-oxo-2h-isoquinoline-3-carboxylate Chemical compound C1=C2N=C(C)SC2=CC(OC=2C=CC3=C(O)N=C(C(=C3C=2)O)C(=O)OCCCC)=C1 HGEPFEGRRLTDEF-UHFFFAOYSA-N 0.000 description 1
- OIYBCBPARJAOCH-UHFFFAOYSA-N butyl 4-hydroxy-6-[(2-methyl-1,3-benzoxazol-6-yl)oxy]-1-oxo-2h-isoquinoline-3-carboxylate Chemical compound C1=C2N=C(C)OC2=CC(OC=2C=CC3=C(O)N=C(C(=C3C=2)O)C(=O)OCCCC)=C1 OIYBCBPARJAOCH-UHFFFAOYSA-N 0.000 description 1
- DWIWLFRROMFMIE-UHFFFAOYSA-N butyl 4-hydroxy-6-[(2-morpholin-4-yl-1,3-benzothiazol-6-yl)oxy]-1-oxo-2h-isoquinoline-3-carboxylate Chemical compound C=1C2=C(O)C(C(=O)OCCCC)=NC(O)=C2C=CC=1OC(C=C1S2)=CC=C1N=C2N1CCOCC1 DWIWLFRROMFMIE-UHFFFAOYSA-N 0.000 description 1
- YWQZGNFNLBVWNZ-UHFFFAOYSA-N butyl 4-hydroxy-6-methoxy-1-oxo-2h-isoquinoline-3-carboxylate Chemical compound C1=CC(OC)=CC2=C(O)C(C(=O)OCCCC)=NC(O)=C21 YWQZGNFNLBVWNZ-UHFFFAOYSA-N 0.000 description 1
- YZNILJKZFSYZCH-UHFFFAOYSA-N butyl 4-hydroxy-7-[(2-methyl-1,3-benzothiazol-6-yl)oxy]-1-oxo-2h-isoquinoline-3-carboxylate Chemical compound C1=C2N=C(C)SC2=CC(OC2=CC3=C(O)N=C(C(=C3C=C2)O)C(=O)OCCCC)=C1 YZNILJKZFSYZCH-UHFFFAOYSA-N 0.000 description 1
- JMHMDLIQBSCTMS-UHFFFAOYSA-N butyl 4-hydroxy-7-[(2-methyl-1,3-benzoxazol-6-yl)oxy]-1-oxo-2h-isoquinoline-3-carboxylate Chemical compound C1=C2N=C(C)OC2=CC(OC2=CC3=C(O)N=C(C(=C3C=C2)O)C(=O)OCCCC)=C1 JMHMDLIQBSCTMS-UHFFFAOYSA-N 0.000 description 1
- IXGVDUGEFJRGNT-UHFFFAOYSA-N butyl 6-(1,3-benzodioxol-5-yloxy)-4-hydroxy-1-oxo-2h-isoquinoline-3-carboxylate Chemical compound C1=C2OCOC2=CC(OC2=CC=C3C(=O)NC(=C(C3=C2)O)C(=O)OCCCC)=C1 IXGVDUGEFJRGNT-UHFFFAOYSA-N 0.000 description 1
- KFNJDGOFBCFOLI-UHFFFAOYSA-N butyl 6-(2,3-dihydro-1-benzofuran-5-yloxy)-4-hydroxy-1-oxo-2h-isoquinoline-3-carboxylate Chemical compound C1=C2OCCC2=CC(OC2=CC=C3C(=O)NC(=C(C3=C2)O)C(=O)OCCCC)=C1 KFNJDGOFBCFOLI-UHFFFAOYSA-N 0.000 description 1
- PESHLBDLZXVOHS-UHFFFAOYSA-N butyl 6-(2-ethyl-6-methylphenoxy)-4-hydroxy-1-oxo-2h-isoquinoline-3-carboxylate Chemical compound C=1C2=C(O)C(C(=O)OCCCC)=NC(O)=C2C=CC=1OC1=C(C)C=CC=C1CC PESHLBDLZXVOHS-UHFFFAOYSA-N 0.000 description 1
- MUIWSSSXUAZJPX-UHFFFAOYSA-N butyl 6-(4-chloro-2,6-dimethylphenoxy)-4-hydroxy-1-oxo-2h-isoquinoline-3-carboxylate Chemical compound C=1C2=C(O)C(C(=O)OCCCC)=NC(O)=C2C=CC=1OC1=C(C)C=C(Cl)C=C1C MUIWSSSXUAZJPX-UHFFFAOYSA-N 0.000 description 1
- OUEHALBFBHKEHP-UHFFFAOYSA-N butyl 6-(benzenesulfonyl)-1-bromo-4-hydroxyisoquinoline-3-carboxylate Chemical compound C=1C2=C(O)C(C(=O)OCCCC)=NC(Br)=C2C=CC=1S(=O)(=O)C1=CC=CC=C1 OUEHALBFBHKEHP-UHFFFAOYSA-N 0.000 description 1
- CFGVCAVTASYCIZ-UHFFFAOYSA-N butyl 6-(benzenesulfonyl)-1-cyano-4-hydroxyisoquinoline-3-carboxylate Chemical compound C=1C2=C(O)C(C(=O)OCCCC)=NC(C#N)=C2C=CC=1S(=O)(=O)C1=CC=CC=C1 CFGVCAVTASYCIZ-UHFFFAOYSA-N 0.000 description 1
- GLDLUMZSRJRADM-UHFFFAOYSA-N butyl 6-(benzenesulfonyl)-4-hydroxyisoquinoline-3-carboxylate Chemical compound C=1C2=C(O)C(C(=O)OCCCC)=NC=C2C=CC=1S(=O)(=O)C1=CC=CC=C1 GLDLUMZSRJRADM-UHFFFAOYSA-N 0.000 description 1
- JYDBYHICTNCRQN-UHFFFAOYSA-N butyl 6-[[2-(dimethylamino)-1,3-benzoxazol-5-yl]oxy]-4-hydroxy-1-oxo-2h-isoquinoline-3-carboxylate Chemical compound C1=C2OC(N(C)C)=NC2=CC(OC=2C=CC3=C(O)N=C(C(=C3C=2)O)C(=O)OCCCC)=C1 JYDBYHICTNCRQN-UHFFFAOYSA-N 0.000 description 1
- RNNBASMHYRHPPV-UHFFFAOYSA-N butyl 6-chloro-1-cyano-4-hydroxyisoquinoline-3-carboxylate Chemical compound C1=CC(Cl)=CC2=C(O)C(C(=O)OCCCC)=NC(C#N)=C21 RNNBASMHYRHPPV-UHFFFAOYSA-N 0.000 description 1
- MKELTKWYUCRHDR-UHFFFAOYSA-N butyl 7-chloro-1-cyano-4-hydroxyisoquinoline-3-carboxylate Chemical compound C1=C(Cl)C=CC2=C(O)C(C(=O)OCCCC)=NC(C#N)=C21 MKELTKWYUCRHDR-UHFFFAOYSA-N 0.000 description 1
- KMGBZBJJOKUPIA-UHFFFAOYSA-N butyl iodide Chemical compound CCCCI KMGBZBJJOKUPIA-UHFFFAOYSA-N 0.000 description 1
- 229910052792 caesium Inorganic materials 0.000 description 1
- ZOAIGCHJWKDIPJ-UHFFFAOYSA-M caesium acetate Chemical compound [Cs+].CC([O-])=O ZOAIGCHJWKDIPJ-UHFFFAOYSA-M 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229960003563 calcium carbonate Drugs 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000001722 carbon compounds Chemical class 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229960004424 carbon dioxide Drugs 0.000 description 1
- 150000007942 carboxylates Chemical group 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 238000010568 chiral column chromatography Methods 0.000 description 1
- 201000002816 chronic venous insufficiency Diseases 0.000 description 1
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 238000012411 cloning technique Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- DIMCZVTXAXZJCA-UHFFFAOYSA-L copper;benzene;trifluoromethanesulfonate Chemical compound [Cu+2].C1=CC=CC=C1.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F DIMCZVTXAXZJCA-UHFFFAOYSA-L 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 125000005171 cycloalkylsulfanyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000001120 cytoprotective effect Effects 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 150000008049 diazo compounds Chemical class 0.000 description 1
- 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 235000021186 dishes Nutrition 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000000913 erythropoietic effect Effects 0.000 description 1
- ZBFRYOCLKLLZBI-UHFFFAOYSA-N ethyl 2-(bromomethyl)-3-(4-fluorophenoxy)benzoate Chemical compound CCOC(=O)C1=CC=CC(OC=2C=CC(F)=CC=2)=C1CBr ZBFRYOCLKLLZBI-UHFFFAOYSA-N 0.000 description 1
- QAUBYJOJNDSRFK-UHFFFAOYSA-N ethyl 2-[(2,4-dimethoxyphenyl)methyl]-4-hydroxy-7-phenylmethoxy-1h-isoquinoline-3-carboxylate Chemical compound C1=C2CN(CC=3C(=CC(OC)=CC=3)OC)C(C(=O)OCC)=C(O)C2=CC=C1OCC1=CC=CC=C1 QAUBYJOJNDSRFK-UHFFFAOYSA-N 0.000 description 1
- FHKSZMJGAMMPLQ-UHFFFAOYSA-N ethyl 2-[1,3-dioxo-5-(4-propoxyphenoxy)isoindol-2-yl]acetate Chemical compound C1=CC(OCCC)=CC=C1OC1=CC=C(C(=O)N(CC(=O)OCC)C2=O)C2=C1 FHKSZMJGAMMPLQ-UHFFFAOYSA-N 0.000 description 1
- UXJLDCDYCARFEM-UHFFFAOYSA-N ethyl 2-[5-(1,3-benzodioxol-5-yloxy)-1,3-dioxoisoindol-2-yl]acetate Chemical compound C1=C2OCOC2=CC(OC2=CC=C3C(=O)N(C(C3=C2)=O)CC(=O)OCC)=C1 UXJLDCDYCARFEM-UHFFFAOYSA-N 0.000 description 1
- UCPIBDDXJWVETE-UHFFFAOYSA-N ethyl 2-[5-(2,3-dihydro-1-benzofuran-5-yloxy)-1,3-dioxoisoindol-2-yl]acetate Chemical compound C1=C2OCCC2=CC(OC2=CC=C3C(=O)N(C(C3=C2)=O)CC(=O)OCC)=C1 UCPIBDDXJWVETE-UHFFFAOYSA-N 0.000 description 1
- ZISKTEULGJFMLS-UHFFFAOYSA-N ethyl 2-[5-[(2-methyl-1,3-benzoxazol-6-yl)oxy]-1,3-dioxoisoindol-2-yl]acetate Chemical compound C1=C2N=C(C)OC2=CC(OC2=CC=C3C(=O)N(C(C3=C2)=O)CC(=O)OCC)=C1 ZISKTEULGJFMLS-UHFFFAOYSA-N 0.000 description 1
- MFEXLYIALOBTLU-UHFFFAOYSA-N ethyl 2-methyl-3-phenoxybenzoate Chemical compound CCOC(=O)C1=CC=CC(OC=2C=CC=CC=2)=C1C MFEXLYIALOBTLU-UHFFFAOYSA-N 0.000 description 1
- CRSBLEHAWICKTD-UHFFFAOYSA-N ethyl 3-(4-fluorophenoxy)-2-methylbenzoate Chemical compound CCOC(=O)C1=CC=CC(OC=2C=CC(F)=CC=2)=C1C CRSBLEHAWICKTD-UHFFFAOYSA-N 0.000 description 1
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
- QRFNJNVVKAMZGD-UHFFFAOYSA-N ethyl 4-[tert-butyl(dimethyl)silyl]oxy-2-methylbenzoate Chemical compound CCOC(=O)C1=CC=C(O[Si](C)(C)C(C)(C)C)C=C1C QRFNJNVVKAMZGD-UHFFFAOYSA-N 0.000 description 1
- KPFPCGFKQNSWSQ-UHFFFAOYSA-N ethyl 4-hydroxy-2-methylbenzoate Chemical compound CCOC(=O)C1=CC=C(O)C=C1C KPFPCGFKQNSWSQ-UHFFFAOYSA-N 0.000 description 1
- ARRWJTJEVDKQDQ-UHFFFAOYSA-N ethyl 4-hydroxy-7-phenylmethoxyisoquinoline-3-carboxylate Chemical compound C1=CC2=C(O)C(C(=O)OCC)=NC=C2C=C1OCC1=CC=CC=C1 ARRWJTJEVDKQDQ-UHFFFAOYSA-N 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- MHYCRLGKOZWVEF-UHFFFAOYSA-N ethyl acetate;hydrate Chemical compound O.CCOC(C)=O MHYCRLGKOZWVEF-UHFFFAOYSA-N 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 150000002332 glycine derivatives Chemical class 0.000 description 1
- 230000002414 glycolytic effect Effects 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000003979 granulating agent Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229960001867 guaiacol Drugs 0.000 description 1
- 238000005534 hematocrit Methods 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 208000014617 hemorrhoid Diseases 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 235000012907 honey Nutrition 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- COQRGFWWJBEXRC-UHFFFAOYSA-N hydron;methyl 2-aminoacetate;chloride Chemical compound Cl.COC(=O)CN COQRGFWWJBEXRC-UHFFFAOYSA-N 0.000 description 1
- 229920001600 hydrophobic polymer Polymers 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 208000015446 immunoglobulin a vasculitis Diseases 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 description 1
- HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 1
- XAAKCCMYRKZRAK-UHFFFAOYSA-N isoquinoline-1-carboxylic acid Chemical class C1=CC=C2C(C(=O)O)=NC=CC2=C1 XAAKCCMYRKZRAK-UHFFFAOYSA-N 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 239000004922 lacquer Substances 0.000 description 1
- 201000011061 large intestine cancer Diseases 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- DIDIDMZGMZGNMJ-UHFFFAOYSA-N methyl 1-bromo-4-hydroxy-5-phenoxyisoquinoline-3-carboxylate Chemical compound C12=C(O)C(C(=O)OC)=NC(Br)=C2C=CC=C1OC1=CC=CC=C1 DIDIDMZGMZGNMJ-UHFFFAOYSA-N 0.000 description 1
- SVFQQJSARIRFFL-UHFFFAOYSA-N methyl 1-bromo-4-hydroxy-8-(2-methoxyphenoxy)isoquinoline-3-carboxylate Chemical compound C=1C=CC2=C(O)C(C(=O)OC)=NC(Br)=C2C=1OC1=CC=CC=C1OC SVFQQJSARIRFFL-UHFFFAOYSA-N 0.000 description 1
- FPSWWEGUWRMCMT-UHFFFAOYSA-N methyl 1-bromo-4-hydroxy-8-(3-methoxyphenoxy)isoquinoline-3-carboxylate Chemical compound C=1C=CC2=C(O)C(C(=O)OC)=NC(Br)=C2C=1OC1=CC=CC(OC)=C1 FPSWWEGUWRMCMT-UHFFFAOYSA-N 0.000 description 1
- PLXWOOSHAPIWHU-UHFFFAOYSA-N methyl 1-bromo-4-hydroxy-8-(4-methoxyphenoxy)isoquinoline-3-carboxylate Chemical compound C=1C=CC2=C(O)C(C(=O)OC)=NC(Br)=C2C=1OC1=CC=C(OC)C=C1 PLXWOOSHAPIWHU-UHFFFAOYSA-N 0.000 description 1
- YYCZQUDUXUFEAA-UHFFFAOYSA-N methyl 1-bromo-4-hydroxy-8-phenoxyisoquinoline-3-carboxylate Chemical compound C=1C=CC2=C(O)C(C(=O)OC)=NC(Br)=C2C=1OC1=CC=CC=C1 YYCZQUDUXUFEAA-UHFFFAOYSA-N 0.000 description 1
- PGEQYJMVGWYHNT-UHFFFAOYSA-N methyl 1-bromo-4-methoxy-8-phenoxyisoquinoline-3-carboxylate Chemical compound C=1C=CC2=C(OC)C(C(=O)OC)=NC(Br)=C2C=1OC1=CC=CC=C1 PGEQYJMVGWYHNT-UHFFFAOYSA-N 0.000 description 1
- VMXNRROGWMKVRH-UHFFFAOYSA-N methyl 1-cyano-4-hydroxy-5-phenoxyisoquinoline-3-carboxylate Chemical compound C12=C(O)C(C(=O)OC)=NC(C#N)=C2C=CC=C1OC1=CC=CC=C1 VMXNRROGWMKVRH-UHFFFAOYSA-N 0.000 description 1
- DWXPEHCTRRAULJ-UHFFFAOYSA-N methyl 1-cyano-4-hydroxy-8-(3-methoxyphenoxy)isoquinoline-3-carboxylate Chemical compound C=1C=CC2=C(O)C(C(=O)OC)=NC(C#N)=C2C=1OC1=CC=CC(OC)=C1 DWXPEHCTRRAULJ-UHFFFAOYSA-N 0.000 description 1
- JWXVTNMDCAWAKR-UHFFFAOYSA-N methyl 1-cyano-4-hydroxy-8-(4-methoxyphenoxy)isoquinoline-3-carboxylate Chemical compound C=1C=CC2=C(O)C(C(=O)OC)=NC(C#N)=C2C=1OC1=CC=C(OC)C=C1 JWXVTNMDCAWAKR-UHFFFAOYSA-N 0.000 description 1
- LUBSJEDVBHETMZ-UHFFFAOYSA-N methyl 1-cyano-4-hydroxy-8-phenoxyisoquinoline-3-carboxylate Chemical compound C=1C=CC2=C(O)C(C(=O)OC)=NC(C#N)=C2C=1OC1=CC=CC=C1 LUBSJEDVBHETMZ-UHFFFAOYSA-N 0.000 description 1
- IYVRHTIYOWNTGK-UHFFFAOYSA-N methyl 1-cyano-5-(4-fluorophenoxy)-4-hydroxyisoquinoline-3-carboxylate Chemical compound C12=C(O)C(C(=O)OC)=NC(C#N)=C2C=CC=C1OC1=CC=C(F)C=C1 IYVRHTIYOWNTGK-UHFFFAOYSA-N 0.000 description 1
- UVLUGMHJHZQUDD-UHFFFAOYSA-N methyl 1-cyano-8-(4-fluorophenoxy)-4-hydroxyisoquinoline-3-carboxylate Chemical compound C=1C=CC2=C(O)C(C(=O)OC)=NC(C#N)=C2C=1OC1=CC=C(F)C=C1 UVLUGMHJHZQUDD-UHFFFAOYSA-N 0.000 description 1
- WYGVSZKPWLTEDF-UHFFFAOYSA-N methyl 2-[1,3-dioxo-5-(2,4,6-trimethylphenoxy)isoindol-2-yl]acetate Chemical compound C1=C2C(=O)N(CC(=O)OC)C(=O)C2=CC=C1OC1=C(C)C=C(C)C=C1C WYGVSZKPWLTEDF-UHFFFAOYSA-N 0.000 description 1
- CRPGIKSVGZJGGE-UHFFFAOYSA-N methyl 2-[5-(2,6-dimethylphenoxy)-1,3-dioxoisoindol-2-yl]acetate Chemical compound C1=C2C(=O)N(CC(=O)OC)C(=O)C2=CC=C1OC1=C(C)C=CC=C1C CRPGIKSVGZJGGE-UHFFFAOYSA-N 0.000 description 1
- RDHIYXUXEPETBW-UHFFFAOYSA-N methyl 2-[5-(2-ethyl-6-methylphenoxy)-1,3-dioxoisoindol-2-yl]acetate Chemical compound CCC1=CC=CC(C)=C1OC1=CC=C(C(=O)N(CC(=O)OC)C2=O)C2=C1 RDHIYXUXEPETBW-UHFFFAOYSA-N 0.000 description 1
- HTOUSYNWVYASGO-UHFFFAOYSA-N methyl 2-[5-(4-chloro-2,6-dimethylphenoxy)-1,3-dioxoisoindol-2-yl]acetate Chemical compound C1=C2C(=O)N(CC(=O)OC)C(=O)C2=CC=C1OC1=C(C)C=C(Cl)C=C1C HTOUSYNWVYASGO-UHFFFAOYSA-N 0.000 description 1
- PERIUSZXZAJLQB-UHFFFAOYSA-N methyl 4-hydroxy-8-(2-methoxyphenoxy)isoquinoline-3-carboxylate Chemical compound C=1C=CC2=C(O)C(C(=O)OC)=NC=C2C=1OC1=CC=CC=C1OC PERIUSZXZAJLQB-UHFFFAOYSA-N 0.000 description 1
- BCVCYQCOIKKNPO-UHFFFAOYSA-N methyl 4-hydroxy-8-(3-methoxyphenoxy)isoquinoline-3-carboxylate Chemical compound C=1C=CC2=C(O)C(C(=O)OC)=NC=C2C=1OC1=CC=CC(OC)=C1 BCVCYQCOIKKNPO-UHFFFAOYSA-N 0.000 description 1
- KSLYTDFPWYHKCZ-UHFFFAOYSA-N methyl 4-hydroxy-8-(4-methoxyphenoxy)isoquinoline-3-carboxylate Chemical compound C=1C=CC2=C(O)C(C(=O)OC)=NC=C2C=1OC1=CC=C(OC)C=C1 KSLYTDFPWYHKCZ-UHFFFAOYSA-N 0.000 description 1
- HBBQRRYZGJVIJX-UHFFFAOYSA-N methyl 4-hydroxy-8-phenoxyisoquinoline-3-carboxylate Chemical compound C=1C=CC2=C(O)C(C(=O)OC)=NC=C2C=1OC1=CC=CC=C1 HBBQRRYZGJVIJX-UHFFFAOYSA-N 0.000 description 1
- BJVHHOKBKCFDPC-UHFFFAOYSA-N methyl 5-(4-fluorophenoxy)-4-hydroxyisoquinoline-3-carboxylate Chemical compound C12=C(O)C(C(=O)OC)=NC=C2C=CC=C1OC1=CC=C(F)C=C1 BJVHHOKBKCFDPC-UHFFFAOYSA-N 0.000 description 1
- JWIRXWTUDGUOAU-UHFFFAOYSA-N methyl 7-benzyl-1-bromo-4-hydroxyisoquinoline-3-carboxylate Chemical compound C1=CC2=C(O)C(C(=O)OC)=NC(Br)=C2C=C1CC1=CC=CC=C1 JWIRXWTUDGUOAU-UHFFFAOYSA-N 0.000 description 1
- ICBBIUYEZODBRJ-UHFFFAOYSA-N methyl 7-benzyl-1-cyano-4-hydroxyisoquinoline-3-carboxylate Chemical compound C1=CC2=C(O)C(C(=O)OC)=NC(C#N)=C2C=C1CC1=CC=CC=C1 ICBBIUYEZODBRJ-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 208000016586 myelodysplastic syndrome with excess blasts Diseases 0.000 description 1
- 206010028537 myelofibrosis Diseases 0.000 description 1
- VYLUUNJZSOFGRJ-UHFFFAOYSA-N n,n-dimethyl-1,3-benzoxazol-2-amine Chemical compound C1=CC=C2OC(N(C)C)=NC2=C1 VYLUUNJZSOFGRJ-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 229920000620 organic polymer Polymers 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- KLAKIAVEMQMVBT-UHFFFAOYSA-N p-hydroxy-phenacyl alcohol Natural products OCC(=O)C1=CC=C(O)C=C1 KLAKIAVEMQMVBT-UHFFFAOYSA-N 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 238000005897 peptide coupling reaction Methods 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 150000008379 phenol ethers Chemical class 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-M phenolate Chemical compound [O-]C1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-M 0.000 description 1
- 229940031826 phenolate Drugs 0.000 description 1
- 229950000688 phenothiazine Drugs 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
- 125000005506 phthalide group Chemical group 0.000 description 1
- 125000005543 phthalimide group Chemical class 0.000 description 1
- 229920006391 phthalonitrile polymer Polymers 0.000 description 1
- 230000010254 physiological adaptation Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229940068886 polyethylene glycol 300 Drugs 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229940100467 polyvinyl acetate phthalate Drugs 0.000 description 1
- 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 1
- JCBJVAJGLKENNC-UHFFFAOYSA-M potassium ethyl xanthate Chemical compound [K+].CCOC([S-])=S JCBJVAJGLKENNC-UHFFFAOYSA-M 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940116317 potato starch Drugs 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 208000003476 primary myelofibrosis Diseases 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 230000029983 protein stabilization Effects 0.000 description 1
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 201000004193 respiratory failure Diseases 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000020874 response to hypoxia Effects 0.000 description 1
- 229940100486 rice starch Drugs 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- SYXYWTXQFUUWLP-UHFFFAOYSA-N sodium;butan-1-olate Chemical compound [Na+].CCCC[O-] SYXYWTXQFUUWLP-UHFFFAOYSA-N 0.000 description 1
- SUBJHSREKVAVAR-UHFFFAOYSA-N sodium;methanol;methanolate Chemical compound [Na+].OC.[O-]C SUBJHSREKVAVAR-UHFFFAOYSA-N 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
- UWHCKJMYHZGTIT-UHFFFAOYSA-N tetraethylene glycol Chemical compound OCCOCCOCCOCCO UWHCKJMYHZGTIT-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 208000035203 thalassemia minor Diseases 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 239000012929 tonicity agent Substances 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 108091006106 transcriptional activators Proteins 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 230000034512 ubiquitination Effects 0.000 description 1
- 238000010798 ubiquitination Methods 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 201000002282 venous insufficiency Diseases 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 102100035070 von Hippel-Lindau disease tumor suppressor Human genes 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
Classifications
-
- 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
- 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
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- 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
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- 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
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Cardiology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Hospice & Palliative Care (AREA)
- Gastroenterology & Hepatology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US76278006P | 2006-01-27 | 2006-01-27 | |
| PCT/US2007/061171 WO2007090068A2 (en) | 2006-01-27 | 2007-01-26 | Cyanoisoquinoline compounds that stabilize hypoxia inducible factor (hif) |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2008009581A true MX2008009581A (es) | 2009-01-07 |
Family
ID=38042727
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2008009581A MX2008009581A (es) | 2006-01-27 | 2007-01-26 | Compuestos de cianoisoquinolina que estabilizan el factor inducible hipoxia (fih). |
Country Status (15)
| Country | Link |
|---|---|
| US (5) | US7928120B2 (enExample) |
| EP (2) | EP2476669A1 (enExample) |
| JP (1) | JP5161793B2 (enExample) |
| KR (2) | KR101446499B1 (enExample) |
| CN (3) | CN103382216B (enExample) |
| AU (1) | AU2007211077B2 (enExample) |
| BR (1) | BRPI0707302B8 (enExample) |
| CA (1) | CA2640435C (enExample) |
| DK (1) | DK2044028T3 (enExample) |
| IL (1) | IL193047A (enExample) |
| MX (1) | MX2008009581A (enExample) |
| NO (1) | NO342678B1 (enExample) |
| RU (1) | RU2457204C2 (enExample) |
| WO (1) | WO2007090068A2 (enExample) |
| ZA (1) | ZA200806752B (enExample) |
Families Citing this family (54)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL1644336T3 (pl) | 2003-06-06 | 2011-07-29 | Fibrogen Inc | Związki heteroarylowe zawierające azot i ich zastosowanie w zwiększaniu poziomu endogennej erytropoetyny |
| US8614204B2 (en) * | 2003-06-06 | 2013-12-24 | Fibrogen, Inc. | Enhanced erythropoiesis and iron metabolism |
| KR101446499B1 (ko) * | 2006-01-27 | 2014-10-06 | 피브로겐, 인크. | 저산소증 유발가능 인자(ｈｉｆ)를 안정시키는 시아노이소퀴놀린 화합물 |
| AU2007218051A1 (en) * | 2006-02-16 | 2007-08-30 | Fibrogen, Inc. | Compounds and methods for treatment of stroke |
| CA2647596C (en) * | 2006-04-04 | 2012-06-12 | Fibrogen, Inc. | Pyrrolo- and thiazolo-pyridine compounds as hif modulators |
| WO2009002533A1 (en) * | 2007-06-27 | 2008-12-31 | The Brigham And Women's Hospital, Inc. | Inflammatory bowel disease therapies |
| US20110039878A1 (en) * | 2007-11-02 | 2011-02-17 | Volkmar Guenzler-Pukall | Methods for reducing blood pressure |
| US8269008B2 (en) * | 2007-12-03 | 2012-09-18 | Fibrogen, Inc. | Oxazolopyridine and isoxazolopyridine derivatives for use in the treatment of HIF-mediated conditions |
| US20110039885A1 (en) * | 2007-12-06 | 2011-02-17 | Fibrogen, Inc. | Methods for increasing endothelial progenitor cells |
| WO2009075826A1 (en) * | 2007-12-07 | 2009-06-18 | Fibrogen, Inc. | Methods for increasing white blood cells |
| EP2252619B1 (en) | 2008-01-11 | 2013-10-09 | Fibrogen, Inc. | Isothiazole-pyridine derivatives as modulators of hif (hypoxia inducible factor) activity |
| WO2009100250A1 (en) | 2008-02-05 | 2009-08-13 | Fibrogen, Inc. | Chromene derivatives and use thereof as hif hydroxylase activity inhibitors |
| ES2524883T3 (es) * | 2008-03-18 | 2014-12-15 | Merck Sharp & Dohme Corp. | 4-Hidroxipirimidina-5-carboxamidas sustituidas |
| WO2009134750A1 (en) | 2008-04-28 | 2009-11-05 | Janssen Pharmaceutica Nv | Benzoimidazoles as prolyl hydroxylase inhibitors |
| EP2334682B1 (en) | 2008-08-20 | 2017-10-04 | Fibrogen, Inc. | Pyrrolo [ 1, 2 -b] pyridazine derivatives and their use as hif modulators |
| WO2010024911A1 (en) * | 2008-08-26 | 2010-03-04 | Fibrogen, Inc. | Methods for increasing neurogenesis |
| EP2370422B1 (en) | 2008-11-14 | 2019-06-05 | Fibrogen, Inc. | Thiochromene derivatives as hif hydroxylase inhibitors |
| EP2483406A2 (en) | 2009-09-30 | 2012-08-08 | President and Fellows of Harvard College | Methods for modulation of autophagy through the modulation of autophagy-inhibiting gene products |
| EP2670750B1 (en) | 2011-02-02 | 2016-09-14 | Fibrogen, Inc. | Naphthyridine derivatives as inhibitors of hypoxia inducible factor |
| GB201102659D0 (en) | 2011-02-15 | 2011-03-30 | Isis Innovation | Assay |
| WO2012150221A2 (de) | 2011-05-04 | 2012-11-08 | Bayer Cropscience Ag | Neue halogenierte benzylalkoholester der cyclopropancarbonsäure als schädlingsbekämpfungsmittel |
| WO2012150208A1 (de) | 2011-05-04 | 2012-11-08 | Bayer Cropscience Ag | Verwendung von substituierten benzylalkoholestern der cyclopropancarbonsäure zur bekämpfung von insektizid-resistenten insekten |
| KR102029951B1 (ko) * | 2011-07-22 | 2019-11-08 | 베이징 베타 파머수티컬 컴퍼니 리미티드 | 프로릴 히드록실라제 억제제로서 화합물의 다형체형, 및 이의 용도 |
| GB201113101D0 (en) | 2011-07-28 | 2011-09-14 | Isis Innovation | Assay |
| ES2818977T3 (es) | 2011-10-25 | 2021-04-14 | Janssen Pharmaceutica Nv | Método para obtener cristales de sal de meglumina de ácido 1-(5,6-dicloro-1H-benzo[d]imidazol-2-il)-1H-pirazol-4-carboxílico |
| NZ700760A (en) | 2012-03-09 | 2016-08-26 | Fibrogen Inc | 4 -hydroxy- isoquinoline compounds as hif hydroxylase inhibitors |
| US8883823B2 (en) | 2012-07-16 | 2014-11-11 | Fibrogen, Inc. | Crystalline forms of a prolyl hydroxylase inhibitor |
| SG10201700873UA (en) | 2012-07-16 | 2017-04-27 | Fibrogen Inc | Crystalline forms of the prolyl hydroxylase inhibitor [(4-hydroxy-1-methyl-7-phenoxy-isoquinoline-3-carbonyl)-amino]-acetic acid |
| CA2879238C (en) | 2012-07-16 | 2021-08-10 | Fibrogen, Inc. | Process for making isoquinoline compounds |
| ES2668694T3 (es) * | 2012-07-27 | 2018-05-21 | Biogen Ma Inc. | Derivados de ácido 1-[7-(cis-4-metil-ciclohexiloxi)-8-trifluorometil-naftalen-2-ilmetil]-piperidin-4-carboxílico como moduladores de autotaxina (ATX) para tratar inflamaciones y trastornos autoinmunitarios |
| JP6437456B2 (ja) * | 2013-01-24 | 2018-12-12 | フィブロジェン インコーポレイテッド | ｛［１−シアノ−５−（４−クロロフェノキシ）−４−ヒドロキシ−イソキノリン−３−カルボニル］−アミノ｝−酢酸の結晶形態 |
| CN110448537A (zh) | 2013-06-06 | 2019-11-15 | 菲布罗根有限公司 | Hif羟化酶抑制剂的药物制剂 |
| EP2915878A1 (en) | 2014-03-07 | 2015-09-09 | Institut Pasteur | Method and device for conserving viable and functional human polymorphonuclear neutrophils |
| WO2016034108A1 (zh) | 2014-09-02 | 2016-03-10 | 广东东阳光药业有限公司 | 喹啉酮类化合物及其应用 |
| TWI770552B (zh) | 2014-12-24 | 2022-07-11 | 美商基利科學股份有限公司 | 喹唑啉化合物 |
| PT3237397T (pt) * | 2014-12-24 | 2019-02-08 | Gilead Sciences Inc | Compostos de isoquinolina para o tratamento de hiv |
| JP6385584B2 (ja) | 2014-12-24 | 2018-09-05 | ギリアード サイエンシーズ， インコーポレイテッド | Ｈｉｖの処置のための縮合ピリミジン化合物 |
| CN106146395B (zh) | 2015-03-27 | 2019-01-01 | 沈阳三生制药有限责任公司 | 3-羟基吡啶化合物、其制备方法及其制药用途 |
| CN104892509B (zh) * | 2015-06-04 | 2018-03-09 | 苏州明锐医药科技有限公司 | 诺得司他的制备方法 |
| KR102333180B1 (ko) * | 2015-08-05 | 2021-11-30 | 삼성전자주식회사 | 플렉서블 디스플레이 장치를 구비한 전자 장치 |
| CN106083720B (zh) * | 2016-02-28 | 2018-09-11 | 深圳市塔吉瑞生物医药有限公司 | 一种取代的杂芳基化合物及包含该化合物的组合物及其用途 |
| CN106478503A (zh) * | 2016-09-29 | 2017-03-08 | 上海勋和医药科技有限公司 | Roxadustat中间体的制备方法 |
| CN107954931B (zh) * | 2016-10-17 | 2021-06-22 | 上海医药集团青岛国风药业股份有限公司 | 一种诺得司他的制备方法 |
| CN108017583B (zh) * | 2016-11-01 | 2021-04-06 | 徐州万邦金桥制药有限公司 | 一种可博美的制备方法 |
| CN110878096A (zh) * | 2018-09-05 | 2020-03-13 | 石药集团中奇制药技术（石家庄）有限公司 | 一种1,7-萘啶类衍生物及其制备方法和用途 |
| IT201800009318A1 (it) * | 2018-10-10 | 2020-04-10 | Luigi Frati | Composizioni antiossidanti |
| AU2019375983A1 (en) | 2018-11-09 | 2021-06-10 | Vivace Therapeutics, Inc. | Bicyclic compounds |
| KR20210133984A (ko) | 2019-02-26 | 2021-11-08 | 바이엘 악티엔게젤샤프트 | 해충 방제제로서의 축합된 비시클릭 헤테로시클릭 유도체 |
| CN113710669A (zh) | 2019-02-26 | 2021-11-26 | 拜耳公司 | 作为农药的稠合双环杂环衍生物 |
| HUE070525T2 (hu) | 2019-04-16 | 2025-06-28 | Vivace Therapeutics Inc | Biciklusos vegyületek |
| TWI865563B (zh) | 2019-07-30 | 2024-12-11 | 德商拜耳動物保健有限公司 | 新穎異喹啉衍生物 |
| CN113292494A (zh) * | 2020-02-24 | 2021-08-24 | 江苏苏中药业集团股份有限公司 | 异喹啉羧酸化合物及其制备方法与应用 |
| US12410140B2 (en) * | 2020-06-19 | 2025-09-09 | Jumpcan (Shanghai) Medical Technology Co., Ltd | Method for synthesis of roxadustat and intermediate thereof, and intermediate thereof |
| CN118414327A (zh) * | 2021-12-17 | 2024-07-30 | 阿克比治疗有限公司 | 作为选择性phd1抑制剂的吡啶酰胺化合物、组合物和使用方法 |
Family Cites Families (58)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4036964A (en) * | 1973-10-11 | 1977-07-19 | Beecham Group Limited | Isocarbostyril-3-carboxylic acid derivatives for the prophylaxis of asthma, hayfever and rhinitis |
| US3989704A (en) * | 1973-10-30 | 1976-11-02 | Sandoz, Inc. | 3-Substituted-4-aryl isoquinolines |
| DE2818423A1 (de) * | 1978-04-27 | 1979-11-08 | Hoechst Ag | Neue isochinolinderivate und verfahren zu ihrer herstellung |
| DE3233424A1 (de) * | 1982-09-09 | 1984-03-15 | Hoechst Ag, 6230 Frankfurt | Isochinolinderivate, verfahren zu ihrer herstellung, pharmazeutische praeparate auf basis dieser verbindungen und ihre verwendung |
| US4559403A (en) * | 1983-05-19 | 1985-12-17 | Hoffmann-La Roche Inc. | Substituted isoquinolines |
| US4584379A (en) * | 1985-01-22 | 1986-04-22 | Merrell Dow Pharmaceuticals Inc. | Isoquinoline thromboxane synthetase inhibitors |
| US4822800A (en) * | 1986-06-09 | 1989-04-18 | Ortho Pharmaceutical Corporation | Isoquinolinol compounds having cardiotonic and phosphodiesterase fraction III inhibiting properties and/or renal vasodilating properties |
| US4966906A (en) * | 1987-11-27 | 1990-10-30 | Hoechst-Roussel Pharmaceuticals Inc. | 1-aryl-3-isoquinolinecarboxamides |
| US4952588A (en) * | 1987-11-27 | 1990-08-28 | Hoechst-Roussel Pharmaceuticals Inc. | 1-aryl-3-quinoline-and 1-aryl-3-isoquinoline-carboxamides |
| EP0532466A3 (en) | 1991-09-12 | 1993-06-16 | Ciba-Geigy Ag | Derivatives of 5-amino-4-hydroxy-hexanoic acid and their therapeutical use |
| EP0626178A1 (de) | 1993-05-17 | 1994-11-30 | Ciba-Geigy Ag | Verwendung von Hemmstoffen von HIV-Aspartatproteasen zur Bekämpfung von Tumorerkrankungen |
| ES2101421T3 (es) | 1993-11-02 | 1997-07-01 | Hoechst Ag | Amidas de acidos carboxilicos heterociclicos sustituidos, su preparacion y su utilizacion como medicamentos. |
| EP0650960B1 (de) * | 1993-11-02 | 1997-03-05 | Hoechst Aktiengesellschaft | Substituierte heterocyclische Carbonsäureamidester, ihre Herstellung und ihre Verwendung als Arzneimittel |
| NZ270267A (en) * | 1993-12-30 | 1997-03-24 | Hoechst Ag | 3-hydroxypyridin-2yl (and -quinolin-2-yl) carboxamide derivatives and pharmaceutical compositions |
| US5563143A (en) | 1994-09-21 | 1996-10-08 | Pfizer Inc. | Catechol diether compounds as inhibitors of TNF release |
| AU4515696A (en) | 1994-12-12 | 1996-07-03 | Merck & Co., Inc. | Substituted 2-aminopyridines as inhibitors of nitric oxide synthase |
| US6297269B1 (en) * | 1995-06-06 | 2001-10-02 | Pfizer Inc. | Substituted n-(indole-2-carbonyl-) amides and derivatives as glycogen phosphorylase inhibitors |
| IL135495A (en) * | 1995-09-28 | 2002-12-01 | Hoechst Ag | Intermediate compounds for the preparation of quinoline-converted amines - 2 - carboxylic acid |
| ES2270475T3 (es) * | 1996-11-27 | 2007-04-01 | Bristol-Myers Squibb Pharma Company | Nuevos antagonistas de receptores de integrina. |
| GB9707830D0 (en) | 1997-04-18 | 1997-06-04 | Smithkline Beecham Plc | Novel compounds |
| AU7526798A (en) | 1997-04-18 | 1998-11-27 | Smithkline Beecham Plc | Acetamide and urea derivatives, process for their preparation and their use in the treatment of cns disorders |
| DE19746287A1 (de) | 1997-10-20 | 1999-04-22 | Hoechst Marion Roussel De Gmbh | Substituierte Isochinolin-2-Carbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel |
| FR2779963A1 (fr) * | 1998-06-22 | 1999-12-24 | Centre Nat Rech Scient | Utilisation d'un compose possedant une affinite pour le recepteur mitochondrial des benzodiazepines en therapie du cancer |
| IT1302677B1 (it) * | 1998-10-15 | 2000-09-29 | Zambon Spa | Derivati benzazinici inibitori della fosfodiesterasi 4 |
| AU4802500A (en) * | 1999-04-26 | 2000-11-10 | Neurogen Corporation | 2-aminoquinolinecarboxamides: neurokinin receptor ligands |
| IT1320162B1 (it) | 2000-02-09 | 2003-11-18 | Rotta Research Lab | Derivati della tirosina ad attivita' anti leucotrienica, procedimentoper la loro preparazione e loro uso farmaceutico. |
| US7622503B2 (en) * | 2000-08-24 | 2009-11-24 | University Of Tennessee Research Foundation | Selective androgen receptor modulators and methods of use thereof |
| FI20002044A0 (fi) * | 2000-09-15 | 2000-09-15 | Orion Yhtymae Oyj | Comt-entsyymiä estäviä naftaleenijohdannaisia |
| DE10110750A1 (de) | 2001-03-07 | 2002-09-12 | Bayer Ag | Neuartige Aminodicarbonsäurederivate mit pharmazeutischen Eigenschaften |
| 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 |
| AU2002312371A1 (en) | 2001-06-13 | 2002-12-23 | Roland W. Burli | Aryl-benzimidazole compounds having antiinfective activity |
| EP1401817A4 (en) * | 2001-06-13 | 2005-11-02 | Genesoft Pharmaceuticals Inc | ISOQUINOLINE COMPOUNDS WITH ANTI-INFECTIOUS ACTIVITY |
| US7105544B2 (en) * | 2001-07-05 | 2006-09-12 | Synaptic Pharmaceutical Corporation | Substituted alkyl amido piperidines |
| JP4558314B2 (ja) | 2001-07-20 | 2010-10-06 | ベーリンガー インゲルハイム （カナダ） リミテッド | ウイルスポリメラーゼインヒビター |
| EP2335700A1 (en) | 2001-07-25 | 2011-06-22 | Boehringer Ingelheim (Canada) Ltd. | Hepatitis C virus polymerase inhibitors with a heterobicylic structure |
| US7294457B2 (en) | 2001-08-07 | 2007-11-13 | Boehringer Ingelheim (Canada) Ltd. | Direct binding assay for identifying inhibitors of HCV polymerase |
| US6930086B2 (en) | 2001-09-25 | 2005-08-16 | Hoffmann-La Roche Inc. | Diglycosylated erythropoietin |
| US6762318B2 (en) * | 2001-12-03 | 2004-07-13 | Novo Nordisk A/S | Glucagon antagonists |
| EP1487472B1 (en) * | 2001-12-06 | 2019-06-26 | Fibrogen, Inc. | Treatment of ischemic or hypoxic conditions using heterocyclic carboxamides |
| GB0206711D0 (en) | 2002-03-21 | 2002-05-01 | Isis Innovation | HIF Inhibitor |
| 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 |
| PL1644336T3 (pl) * | 2003-06-06 | 2011-07-29 | Fibrogen Inc | Związki heteroarylowe zawierające azot i ich zastosowanie w zwiększaniu poziomu endogennej erytropoetyny |
| WO2005007192A2 (en) * | 2003-06-06 | 2005-01-27 | Fibrogen, Inc. | Cytoprotection through the use of hif hydroxylase inhibitors |
| US8614204B2 (en) | 2003-06-06 | 2013-12-24 | Fibrogen, Inc. | Enhanced erythropoiesis and iron metabolism |
| EP1646611A1 (en) | 2003-07-15 | 2006-04-19 | Merck & Co., Inc. | Hydroxypyridine cgrp receptor antagonists |
| US7208601B2 (en) * | 2003-08-08 | 2007-04-24 | Mjalli Adnan M M | Aryl and heteroaryl compounds, compositions, and methods of use |
| CN1832920A (zh) | 2003-08-08 | 2006-09-13 | 特兰斯泰克制药公司 | 芳基和杂芳基化合物,组合物及其使用方法 |
| NZ551632A (en) | 2004-05-28 | 2009-09-25 | Fibrogen Inc | HIF prolyl hydroxylase activity assay |
| US7248053B2 (en) * | 2004-07-15 | 2007-07-24 | Powerprecise Solutions, Inc. | One time operating state detecting method and apparatus |
| EP1676834A1 (en) | 2004-12-30 | 2006-07-05 | Sanofi-Aventis Deutschland GmbH | Fused bicyclic carboxamide derivates for use as CXCR2 inhibitors in the treatment of inflammation |
| CN101166745A (zh) * | 2005-03-02 | 2008-04-23 | 菲布罗根有限公司 | 噻吩并吡啶化合物和其使用方法 |
| EP1893186A2 (en) * | 2005-06-06 | 2008-03-05 | Fibrogen, Inc. | Improved treatment for anemia using a hif-alpha stabilising agent |
| BRPI0611670A2 (pt) * | 2005-06-15 | 2016-11-16 | Fibrogen Inc | método para o tratamento ou prevenção de câncer em um indivíduo |
| KR101446499B1 (ko) * | 2006-01-27 | 2014-10-06 | 피브로겐, 인크. | 저산소증 유발가능 인자(ｈｉｆ)를 안정시키는 시아노이소퀴놀린 화합물 |
| CA2647596C (en) * | 2006-04-04 | 2012-06-12 | Fibrogen, Inc. | Pyrrolo- and thiazolo-pyridine compounds as hif modulators |
| US7713986B2 (en) * | 2006-06-15 | 2010-05-11 | Fibrogen, Inc. | Compounds and methods for treatment of chemotherapy-induced anemia |
| US20070293575A1 (en) * | 2006-06-15 | 2007-12-20 | Fibrogen, Inc. | Compounds and methods for treatment of cancer-related anemia |
-
2007
- 2007-01-26 KR KR1020087020971A patent/KR101446499B1/ko not_active Expired - Fee Related
- 2007-01-26 AU AU2007211077A patent/AU2007211077B2/en not_active Ceased
- 2007-01-26 BR BRPI0707302A patent/BRPI0707302B8/pt not_active IP Right Cessation
- 2007-01-26 US US11/627,906 patent/US7928120B2/en active Active
- 2007-01-26 RU RU2008134664/04A patent/RU2457204C2/ru active IP Right Revival
- 2007-01-26 ZA ZA200806752A patent/ZA200806752B/xx unknown
- 2007-01-26 WO PCT/US2007/061171 patent/WO2007090068A2/en not_active Ceased
- 2007-01-26 JP JP2008552602A patent/JP5161793B2/ja not_active Expired - Fee Related
- 2007-01-26 CN CN201310239635.2A patent/CN103382216B/zh active Active
- 2007-01-26 DK DK07717454.8T patent/DK2044028T3/da active
- 2007-01-26 KR KR1020147017534A patent/KR20140089446A/ko not_active Ceased
- 2007-01-26 EP EP11194165A patent/EP2476669A1/en not_active Withdrawn
- 2007-01-26 CA CA2640435A patent/CA2640435C/en active Active
- 2007-01-26 EP EP07717454A patent/EP2044028B1/en active Active
- 2007-01-26 CN CN2007800035992A patent/CN101374815B/zh active Active
- 2007-01-26 CN CN201110220665.XA patent/CN102351791B/zh active Active
- 2007-01-26 MX MX2008009581A patent/MX2008009581A/es active IP Right Grant
-
2008
- 2008-07-24 IL IL193047A patent/IL193047A/en active IP Right Grant
- 2008-08-25 NO NO20083658A patent/NO342678B1/no unknown
-
2011
- 2011-03-07 US US13/042,281 patent/US20110212959A1/en not_active Abandoned
-
2012
- 2012-03-26 US US13/430,568 patent/US8759373B2/en active Active
-
2014
- 2014-05-28 US US14/289,573 patent/US9174976B2/en active Active
-
2015
- 2015-09-21 US US14/860,560 patent/US20160009653A1/en not_active Abandoned
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2640435C (en) | Cyanoisoquinoline compounds that stabilize hypoxia inducible factor (hif) | |
| US8952160B2 (en) | Isothiazole-pyridine derivatives as modulators of HIF (hypoxia inducible factor) activity | |
| US7696223B2 (en) | Pyrrolo- and Thiazolo-pyridine compounds, and methods of use thereof | |
| US9149476B2 (en) | Thiochromene derivatives as HIF hydroxylase inhibitors | |
| CA2866556A1 (en) | 4 -hydroxy-isoquinoline compounds as hif hydroxylase inhibitors | |
| WO2010022240A1 (en) | Pyrrolo [ 1, 2 -b] pyridazine derivatives and their use as hif modulators | |
| JP2011225583A (ja) | チエノピリジン化合物およびその使用方法 | |
| CN107840826B (zh) | 1h-吲唑类衍生物及其作为ido抑制剂的用途 | |
| HK1129114B (en) | Cyanoisoquinoline compounds that stabilize hypoxia inducible factor (hif) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| HH | Correction or change in general | ||
| FG | Grant or registration |