ES2442847T3 - Quinolonas y azaquinolonas que inhiben la prolil hidroxilasa - Google Patents

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Publication number

ES2442847T3

ES2442847T3 ES08743008.8T ES08743008T ES2442847T3 ES 2442847 T3 ES2442847 T3 ES 2442847T3 ES 08743008 T ES08743008 T ES 08743008T ES 2442847 T3 ES2442847 T3 ES 2442847T3

Authority

ES

Spain

Prior art keywords

methyl

hydroxy

oxo

oxobutanoic acid

dihydroquinolin

Prior art date

2007-04-18

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

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• 102000004079 Prolyl Hydroxylases Human genes 0.000 title description 23
• 108010043005 Prolyl Hydroxylases Proteins 0.000 title description 23
• 150000007660 quinolones Chemical class 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 245
• 239000000203 mixture Substances 0.000 claims abstract description 89
• -1 perhaloalkyl Chemical group 0.000 claims abstract description 72
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 50
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 45
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 42
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 38
• 125000003118 aryl group Chemical group 0.000 claims abstract description 34
• 150000003839 salts Chemical class 0.000 claims abstract description 32
• 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 19
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims abstract description 18
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 15
• 125000003342 alkenyl group Chemical group 0.000 claims abstract description 14
• 125000000304 alkynyl group Chemical group 0.000 claims abstract description 14
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 13
• 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 12
• 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 12
• 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 12
• 125000002947 alkylene group Chemical group 0.000 claims abstract description 11
• 125000004450 alkenylene group Chemical group 0.000 claims abstract description 10
• 125000004419 alkynylene group Chemical group 0.000 claims abstract description 10
• 125000004415 heterocyclylalkyl group Chemical group 0.000 claims abstract description 10
• 229910052740 iodine Inorganic materials 0.000 claims abstract description 9
• 239000012453 solvate Substances 0.000 claims abstract description 9
• 125000005017 substituted alkenyl group Chemical group 0.000 claims abstract description 8
• 125000004426 substituted alkynyl group Chemical group 0.000 claims abstract description 8
• 229910052794 bromium Inorganic materials 0.000 claims abstract description 5
• 229910052801 chlorine Inorganic materials 0.000 claims abstract description 5
• 229910052731 fluorine Inorganic materials 0.000 claims abstract description 5
• JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims abstract description 4
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims abstract 4
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 55
• 238000002360 preparation method Methods 0.000 claims description 40
• 102100037249 Egl nine homolog 1 Human genes 0.000 claims description 33
• 101710111663 Egl nine homolog 1 Proteins 0.000 claims description 33
• 239000003814 drug Substances 0.000 claims description 23
• 208000028867 ischemia Diseases 0.000 claims description 15
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
• 239000008194 pharmaceutical composition Substances 0.000 claims description 14
• 239000002253 acid Substances 0.000 claims description 12
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 12
• 102000003951 Erythropoietin Human genes 0.000 claims description 11
• 108090000394 Erythropoietin Proteins 0.000 claims description 11
• 210000004369 blood Anatomy 0.000 claims description 11
• 239000008280 blood Substances 0.000 claims description 11
• 229940105423 erythropoietin Drugs 0.000 claims description 11
• 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 description 11
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
• 206010021143 Hypoxia Diseases 0.000 claims description 9
• 229910052757 nitrogen Inorganic materials 0.000 claims description 9
• FAWSLMNFZXXCSE-UHFFFAOYSA-N 4-(7,8-difluoro-4-hydroxy-1-methyl-2-oxoquinolin-3-yl)-4-oxobutanoic acid Chemical compound FC1=CC=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C1F FAWSLMNFZXXCSE-UHFFFAOYSA-N 0.000 claims description 8
• 230000007954 hypoxia Effects 0.000 claims description 7
• YOPREHPEFDOGBH-UHFFFAOYSA-N 4-(4-hydroxy-1-methyl-2-oxo-6-phenyl-1,8-naphthyridin-3-yl)-4-oxobutanoic acid Chemical compound C1=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=NC=C1C1=CC=CC=C1 YOPREHPEFDOGBH-UHFFFAOYSA-N 0.000 claims description 6
• UCDZNCXFBWBDBT-UHFFFAOYSA-N 4-[3-(3-carboxypropanoyl)-4-hydroxy-1-methyl-2-oxoquinolin-7-yl]benzoic acid Chemical compound C=1C=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=CC=1C1=CC=C(C(O)=O)C=C1 UCDZNCXFBWBDBT-UHFFFAOYSA-N 0.000 claims description 6
• OVPREICYZRSPCE-UHFFFAOYSA-N 6-(3-carboxypropanoyl)-5-hydroxy-8-methyl-7-oxo-1,8-naphthyridine-3-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=N1 OVPREICYZRSPCE-UHFFFAOYSA-N 0.000 claims description 6
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
• MEVOFGCHWMIIFA-UHFFFAOYSA-N 4-[4-hydroxy-1-methyl-2-oxo-6-(trifluoromethyl)-1,8-naphthyridin-3-yl]-4-oxobutanoic acid Chemical compound C1=C(C(F)(F)F)C=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=N1 MEVOFGCHWMIIFA-UHFFFAOYSA-N 0.000 claims description 5
• FCBGADAOCBIFSG-UHFFFAOYSA-N 3-(3-carboxypropanoyl)-4-hydroxy-1-methyl-2-oxo-1,7-naphthyridine-6-carboxylic acid Chemical compound N1=C(C(O)=O)C=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C1 FCBGADAOCBIFSG-UHFFFAOYSA-N 0.000 claims description 4
• GBFBFKZVMZZMOO-UHFFFAOYSA-N 3-(3-carboxypropanoyl)-4-hydroxy-1-methyl-2-oxoquinoline-6-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C1 GBFBFKZVMZZMOO-UHFFFAOYSA-N 0.000 claims description 4
• SJZXVRXQWCLHRN-UHFFFAOYSA-N 3-(3-carboxypropanoyl)-4-hydroxy-1-methyl-2-oxoquinoline-7-carboxylic acid Chemical compound OC(=O)C1=CC=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C1 SJZXVRXQWCLHRN-UHFFFAOYSA-N 0.000 claims description 4
• JHZDQKFXZSDGEJ-UHFFFAOYSA-N 4-(1-benzyl-4-hydroxy-2-oxo-1,8-naphthyridin-3-yl)-4-oxobutanoic acid Chemical compound O=C1C(C(=O)CCC(=O)O)=C(O)C2=CC=CN=C2N1CC1=CC=CC=C1 JHZDQKFXZSDGEJ-UHFFFAOYSA-N 0.000 claims description 4
• HTFCBCOEBHSEAY-UHFFFAOYSA-N 4-(1-benzyl-4-hydroxy-2-oxoquinolin-3-yl)-4-oxobutanoic acid Chemical compound O=C1C(C(=O)CCC(=O)O)=C(O)C2=CC=CC=C2N1CC1=CC=CC=C1 HTFCBCOEBHSEAY-UHFFFAOYSA-N 0.000 claims description 4
• NGQMOMCWKBIGPS-UHFFFAOYSA-N 4-(1-benzyl-7,8-difluoro-4-hydroxy-2-oxoquinolin-3-yl)-4-oxobutanoic acid Chemical compound O=C1C(C(=O)CCC(=O)O)=C(O)C2=CC=C(F)C(F)=C2N1CC1=CC=CC=C1 NGQMOMCWKBIGPS-UHFFFAOYSA-N 0.000 claims description 4
• APZBXINEKFBHMY-UHFFFAOYSA-N 4-(1-benzyl-7-bromo-4-hydroxy-2-oxoquinolin-3-yl)-4-oxobutanoic acid Chemical compound O=C1C(C(=O)CCC(=O)O)=C(O)C2=CC=C(Br)C=C2N1CC1=CC=CC=C1 APZBXINEKFBHMY-UHFFFAOYSA-N 0.000 claims description 4
• ZDSHJJSUYHSJON-UHFFFAOYSA-N 4-(4-hydroxy-1-methyl-2-oxo-1,5-naphthyridin-3-yl)-4-oxobutanoic acid Chemical compound C1=CN=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C1 ZDSHJJSUYHSJON-UHFFFAOYSA-N 0.000 claims description 4
• RETQKIVXWLHCTB-UHFFFAOYSA-N 4-(4-hydroxy-1-methyl-2-oxo-1,7-naphthyridin-3-yl)-4-oxobutanoic acid Chemical compound N1=CC=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C1 RETQKIVXWLHCTB-UHFFFAOYSA-N 0.000 claims description 4
• DZVKKDNRFVPAPW-UHFFFAOYSA-N 4-(4-hydroxy-1-methyl-2-oxo-1,8-naphthyridin-3-yl)-4-oxobutanoic acid Chemical compound C1=CC=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=N1 DZVKKDNRFVPAPW-UHFFFAOYSA-N 0.000 claims description 4
• VPMJBCORSOGLST-UHFFFAOYSA-N 4-(4-hydroxy-1-methyl-2-oxo-6-phenyl-1,7-naphthyridin-3-yl)-4-oxobutanoic acid Chemical compound C1=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=CN=C1C1=CC=CC=C1 VPMJBCORSOGLST-UHFFFAOYSA-N 0.000 claims description 4
• LPEQEFOPSJSTKP-UHFFFAOYSA-N 4-(4-hydroxy-1-methyl-2-oxo-6-phenylquinolin-3-yl)-4-oxobutanoic acid Chemical compound C1=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=CC=C1C1=CC=CC=C1 LPEQEFOPSJSTKP-UHFFFAOYSA-N 0.000 claims description 4
• IUNXGLCEASABPB-UHFFFAOYSA-N 4-(4-hydroxy-1-methyl-2-oxo-6-thiophen-3-yl-1,8-naphthyridin-3-yl)-4-oxobutanoic acid Chemical compound C1=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=NC=C1C=1C=CSC=1 IUNXGLCEASABPB-UHFFFAOYSA-N 0.000 claims description 4
• KEBLJXILKZQOQQ-UHFFFAOYSA-N 4-(4-hydroxy-1-methyl-2-oxo-7-phenylquinolin-3-yl)-4-oxobutanoic acid Chemical compound C=1C=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=CC=1C1=CC=CC=C1 KEBLJXILKZQOQQ-UHFFFAOYSA-N 0.000 claims description 4
• TUKIBJBFQBPBIT-UHFFFAOYSA-N 4-(4-hydroxy-1-methyl-2-oxo-7-thiophen-2-yl-1,5-naphthyridin-3-yl)-4-oxobutanoic acid Chemical compound C=1N=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=CC=1C1=CC=CS1 TUKIBJBFQBPBIT-UHFFFAOYSA-N 0.000 claims description 4
• VOIIANIAJYFQRM-UHFFFAOYSA-N 4-(4-hydroxy-1-methyl-2-oxo-7-thiophen-2-ylquinolin-3-yl)-4-oxobutanoic acid Chemical compound C=1C=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=CC=1C1=CC=CS1 VOIIANIAJYFQRM-UHFFFAOYSA-N 0.000 claims description 4
• PEHGRZOSSVYJIL-UHFFFAOYSA-N 4-(4-hydroxy-1-methyl-2-oxo-7-thiophen-3-yl-1,5-naphthyridin-3-yl)-4-oxobutanoic acid Chemical compound C=1N=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=CC=1C=1C=CSC=1 PEHGRZOSSVYJIL-UHFFFAOYSA-N 0.000 claims description 4
• NOPKKRQZPIYRIJ-UHFFFAOYSA-N 4-(4-hydroxy-1-methyl-2-oxo-7-thiophen-3-ylquinolin-3-yl)-4-oxobutanoic acid Chemical compound C=1C=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=CC=1C=1C=CSC=1 NOPKKRQZPIYRIJ-UHFFFAOYSA-N 0.000 claims description 4
• GWLFXLKSLZHOBL-UHFFFAOYSA-N 4-(4-hydroxy-1-methyl-2-oxoquinolin-3-yl)-4-oxobutanoic acid Chemical compound C1=CC=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C1 GWLFXLKSLZHOBL-UHFFFAOYSA-N 0.000 claims description 4
• QTSLKEWTNYUSLS-UHFFFAOYSA-N 4-(4-hydroxy-6-iodo-1-methyl-2-oxoquinolin-3-yl)-4-oxobutanoic acid Chemical compound C1=C(I)C=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C1 QTSLKEWTNYUSLS-UHFFFAOYSA-N 0.000 claims description 4
• DCJKRKYLAIKIQM-UHFFFAOYSA-N 4-(5-bromo-4-hydroxy-1-methyl-2-oxoquinolin-3-yl)-4-oxobutanoic acid Chemical compound C1=CC(Br)=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C1 DCJKRKYLAIKIQM-UHFFFAOYSA-N 0.000 claims description 4
• QMQPHLFJRRTUJR-UHFFFAOYSA-N 4-(6-cyclopentyl-4-hydroxy-1-methyl-2-oxo-1,8-naphthyridin-3-yl)-4-oxobutanoic acid Chemical compound C1=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=NC=C1C1CCCC1 QMQPHLFJRRTUJR-UHFFFAOYSA-N 0.000 claims description 4
• FEKWXSVPTLHHCK-UHFFFAOYSA-N 4-(6-cyclopropyl-7,8-difluoro-4-hydroxy-1-methyl-2-oxoquinolin-3-yl)-4-oxobutanoic acid Chemical compound C1=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C(F)C(F)=C1C1CC1 FEKWXSVPTLHHCK-UHFFFAOYSA-N 0.000 claims description 4
• QATCZKHAJFAEST-UHFFFAOYSA-N 4-(7,8-dichloro-4-hydroxy-1-methyl-2-oxoquinolin-3-yl)-4-oxobutanoic acid Chemical compound ClC1=CC=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C1Cl QATCZKHAJFAEST-UHFFFAOYSA-N 0.000 claims description 4
• MUOXPOVTHZBCCK-UHFFFAOYSA-N 4-(7,8-difluoro-4-hydroxy-1-methyl-2-oxo-6-phenylquinolin-3-yl)-4-oxobutanoic acid Chemical compound C1=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C(F)C(F)=C1C1=CC=CC=C1 MUOXPOVTHZBCCK-UHFFFAOYSA-N 0.000 claims description 4
• PXMYFGGKSJFUTN-UHFFFAOYSA-N 4-(7,8-difluoro-4-hydroxy-6-iodo-1-methyl-2-oxoquinolin-3-yl)-4-oxobutanoic acid Chemical compound FC1=C(I)C=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C1F PXMYFGGKSJFUTN-UHFFFAOYSA-N 0.000 claims description 4
• DXIRWIQKSNIGMX-UHFFFAOYSA-N 4-(7-bromo-4-hydroxy-1-methyl-2-oxo-1,5-naphthyridin-3-yl)-4-oxobutanoic acid Chemical compound BrC1=CN=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C1 DXIRWIQKSNIGMX-UHFFFAOYSA-N 0.000 claims description 4
• GZQNECCMESWBBW-UHFFFAOYSA-N 4-(7-bromo-4-hydroxy-1-methyl-2-oxoquinolin-3-yl)-4-oxobutanoic acid Chemical compound BrC1=CC=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C1 GZQNECCMESWBBW-UHFFFAOYSA-N 0.000 claims description 4
• GRYVYFQDXHKMOA-UHFFFAOYSA-N 4-(8-bromo-4-hydroxy-1-methyl-2-oxoquinolin-3-yl)-4-oxobutanoic acid Chemical compound C1=CC=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C1Br GRYVYFQDXHKMOA-UHFFFAOYSA-N 0.000 claims description 4
• PTNUYKWJXPHMIE-UHFFFAOYSA-N 4-(8-chloro-7-fluoro-4-hydroxy-1-methyl-2-oxoquinolin-3-yl)-4-oxobutanoic acid Chemical compound FC1=CC=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C1Cl PTNUYKWJXPHMIE-UHFFFAOYSA-N 0.000 claims description 4
• IEBQSKIRCTVZSW-UHFFFAOYSA-N 4-[1-benzyl-4-hydroxy-2-oxo-7-(trifluoromethyl)-1,8-naphthyridin-3-yl]-4-oxobutanoic acid Chemical compound O=C1C(C(=O)CCC(=O)O)=C(O)C2=CC=C(C(F)(F)F)N=C2N1CC1=CC=CC=C1 IEBQSKIRCTVZSW-UHFFFAOYSA-N 0.000 claims description 4
• YQIBBCNNLAFOBG-UHFFFAOYSA-N 4-[4-hydroxy-1-methyl-2-oxo-6-(oxolan-2-yl)-1,8-naphthyridin-3-yl]-4-oxobutanoic acid Chemical compound C1=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=NC=C1C1CCCO1 YQIBBCNNLAFOBG-UHFFFAOYSA-N 0.000 claims description 4
• UPBRHIDKCQHDLT-UHFFFAOYSA-N 4-[4-hydroxy-1-methyl-2-oxo-6-(oxolan-3-yl)-1,8-naphthyridin-3-yl]-4-oxobutanoic acid Chemical compound C1=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=NC=C1C1CCOC1 UPBRHIDKCQHDLT-UHFFFAOYSA-N 0.000 claims description 4
• RJQNWRTZVLCROH-UHFFFAOYSA-N 4-[4-hydroxy-1-methyl-2-oxo-6-phenyl-7-(trifluoromethyl)quinolin-3-yl]-4-oxobutanoic acid Chemical compound C1=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=CC(C(F)(F)F)=C1C1=CC=CC=C1 RJQNWRTZVLCROH-UHFFFAOYSA-N 0.000 claims description 4
• FKGWGYJZENCLSV-UHFFFAOYSA-N 4-[4-hydroxy-1-methyl-2-oxo-7-(trifluoromethyl)quinolin-3-yl]-4-oxobutanoic acid Chemical compound FC(F)(F)C1=CC=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C1 FKGWGYJZENCLSV-UHFFFAOYSA-N 0.000 claims description 4
• NOWNKXMCVAWQOE-UHFFFAOYSA-N 4-[4-hydroxy-1-methyl-6-(oxan-2-yl)-2-oxo-1,8-naphthyridin-3-yl]-4-oxobutanoic acid Chemical compound C1=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=NC=C1C1CCCCO1 NOWNKXMCVAWQOE-UHFFFAOYSA-N 0.000 claims description 4
• SRWZDWZSTGIVCY-UHFFFAOYSA-N 4-[6-(2-fluorophenyl)-4-hydroxy-1-methyl-2-oxo-1,8-naphthyridin-3-yl]-4-oxobutanoic acid Chemical compound C1=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=NC=C1C1=CC=CC=C1F SRWZDWZSTGIVCY-UHFFFAOYSA-N 0.000 claims description 4
• TWXKADPXTMSXEQ-UHFFFAOYSA-N 4-[6-(2-fluorophenyl)-4-hydroxy-1-methyl-2-oxoquinolin-3-yl]-4-oxobutanoic acid Chemical compound C1=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=CC=C1C1=CC=CC=C1F TWXKADPXTMSXEQ-UHFFFAOYSA-N 0.000 claims description 4
• TZUKYOGAFJXCOU-UHFFFAOYSA-N 4-[6-(3-carboxypropanoyl)-5-hydroxy-8-methyl-7-oxo-1,8-naphthyridin-3-yl]benzoic acid Chemical compound C1=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=NC=C1C1=CC=C(C(O)=O)C=C1 TZUKYOGAFJXCOU-UHFFFAOYSA-N 0.000 claims description 4
• ZGPHJWXDVGLPMW-UHFFFAOYSA-N 4-[6-(3-fluorophenyl)-4-hydroxy-1-methyl-2-oxo-1,8-naphthyridin-3-yl]-4-oxobutanoic acid Chemical compound C1=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=NC=C1C1=CC=CC(F)=C1 ZGPHJWXDVGLPMW-UHFFFAOYSA-N 0.000 claims description 4
• SNACNZCDPIFFGM-UHFFFAOYSA-N 4-[6-(3-fluorophenyl)-4-hydroxy-1-methyl-2-oxoquinolin-3-yl]-4-oxobutanoic acid Chemical compound C1=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=CC=C1C1=CC=CC(F)=C1 SNACNZCDPIFFGM-UHFFFAOYSA-N 0.000 claims description 4
• LEYLCDYLVZPLRI-UHFFFAOYSA-N 4-[6-(4-fluorophenyl)-4-hydroxy-1-methyl-2-oxo-1,8-naphthyridin-3-yl]-4-oxobutanoic acid Chemical compound C1=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=NC=C1C1=CC=C(F)C=C1 LEYLCDYLVZPLRI-UHFFFAOYSA-N 0.000 claims description 4
• JVELYIINHUGAQE-UHFFFAOYSA-N 4-[6-(4-fluorophenyl)-4-hydroxy-1-methyl-2-oxoquinolin-3-yl]-4-oxobutanoic acid Chemical compound C1=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=CC=C1C1=CC=C(F)C=C1 JVELYIINHUGAQE-UHFFFAOYSA-N 0.000 claims description 4
• IFYOZIRVWKVSKM-UHFFFAOYSA-N 4-[6-cyclopropyl-4-hydroxy-1-methyl-2-oxo-7-(trifluoromethyl)quinolin-3-yl]-4-oxobutanoic acid Chemical compound C1=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=CC(C(F)(F)F)=C1C1CC1 IFYOZIRVWKVSKM-UHFFFAOYSA-N 0.000 claims description 4
• SAPFJHPRRFUKIM-UHFFFAOYSA-N 4-[7,8-difluoro-4-hydroxy-1-methyl-2-oxo-6-(oxolan-3-yl)quinolin-3-yl]-4-oxobutanoic acid Chemical compound C1=C2C(O)=C(C(=O)CCC(O)=O)C(=O)N(C)C2=C(F)C(F)=C1C1CCOC1 SAPFJHPRRFUKIM-UHFFFAOYSA-N 0.000 claims description 4
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