CA2675252C - N-substituted glycine derivatives: hydroxylase inhibitors - Google Patents

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Publication number

CA2675252C

CA2675252C CA2675252A CA2675252A CA2675252C CA 2675252 C CA2675252 C CA 2675252C CA 2675252 A CA2675252 A CA 2675252A CA 2675252 A CA2675252 A CA 2675252A CA 2675252 C CA2675252 C CA 2675252C

Authority

CA

Canada

Prior art keywords

oxo

dihydro

glycine

hydroxy

carbonyl

Prior art date

2007-01-12

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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• 108010049175 N-substituted Glycines Proteins 0.000 title abstract description 4
• 150000002332 glycine derivatives Chemical class 0.000 title abstract description 4
• 102000008109 Mixed Function Oxygenases Human genes 0.000 title description 3
• 108010074633 Mixed Function Oxygenases Proteins 0.000 title description 3
• 239000003112 inhibitor Substances 0.000 title description 3
• 208000007502 anemia Diseases 0.000 claims abstract description 15
• 150000001875 compounds Chemical class 0.000 claims description 425
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 162
• 230000002829 reductive effect Effects 0.000 claims description 116
• -1 5-hydroxy-6-(1-methylethyl)-3-oxo-2-{[4'-(trifluoromethyl)-2-biphenylyl]methyl}-2,3-dihydro-4-pyridazinyl Chemical group 0.000 claims description 59
• 150000003839 salts Chemical class 0.000 claims description 31
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 21
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 15
• 239000008194 pharmaceutical composition Substances 0.000 claims description 15
• WVQKWBBINAVAHK-UHFFFAOYSA-N 2-[[2-[(4-bromo-2-fluorophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=C(Br)C=C1F WVQKWBBINAVAHK-UHFFFAOYSA-N 0.000 claims description 10
• 238000004519 manufacturing process Methods 0.000 claims description 10
• BPFLAJJDOYQJEP-UHFFFAOYSA-N 2-[[2-[(4-bromophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=C(Br)C=C1 BPFLAJJDOYQJEP-UHFFFAOYSA-N 0.000 claims description 9
• VDVLEQVPLSQREQ-UHFFFAOYSA-N 2-[[2-[(2-bromophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=CC=C1Br VDVLEQVPLSQREQ-UHFFFAOYSA-N 0.000 claims description 8
• 239000003085 diluting agent Substances 0.000 claims description 7
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
• 239000003814 drug Substances 0.000 claims description 6
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
• 102000003951 Erythropoietin Human genes 0.000 claims description 5
• 108090000394 Erythropoietin Proteins 0.000 claims description 5
• 229940105423 erythropoietin Drugs 0.000 claims description 5
• 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 5
• IMQPYVPFWOAQOP-UHFFFAOYSA-N 2-[[2-[(3-bromophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=CC(Br)=C1 IMQPYVPFWOAQOP-UHFFFAOYSA-N 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• CASXZMAHBJFQIZ-UHFFFAOYSA-N 2-[[2-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=C(C(F)(F)F)C=C1F CASXZMAHBJFQIZ-UHFFFAOYSA-N 0.000 claims description 3
• ULIQJGDMWQPTAA-UHFFFAOYSA-N 2-[[5-hydroxy-2-[[2-(4-nitrophenyl)phenyl]methyl]-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=CC=C1C1=CC=C([N+]([O-])=O)C=C1 ULIQJGDMWQPTAA-UHFFFAOYSA-N 0.000 claims description 3
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
• UZNSRZNFJZBRFE-UHFFFAOYSA-N 2-[(4-hydroxy-6-oxo-3-propan-2-yl-1h-pyridazine-5-carbonyl)amino]acetic acid Chemical compound CC(C)C1=NNC(=O)C(C(=O)NCC(O)=O)=C1O UZNSRZNFJZBRFE-UHFFFAOYSA-N 0.000 claims description 2
• IXOWKENJMBHUQM-UHFFFAOYSA-N 2-[(4-hydroxy-6-oxo-3-thiophen-2-yl-1h-pyridazine-5-carbonyl)amino]acetic acid Chemical compound N1C(=O)C(C(=O)NCC(=O)O)=C(O)C(C=2SC=CC=2)=N1 IXOWKENJMBHUQM-UHFFFAOYSA-N 0.000 claims description 2
• WEWQENZTNCDJGM-UHFFFAOYSA-N 2-[[2-[(4-tert-butylphenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=C(C(C)(C)C)C=C1 WEWQENZTNCDJGM-UHFFFAOYSA-N 0.000 claims description 2
• DHGSJWBFHVGHDG-UHFFFAOYSA-N 2-[[2-[[2-(4-aminophenyl)phenyl]methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=CC=C1C1=CC=C(N)C=C1 DHGSJWBFHVGHDG-UHFFFAOYSA-N 0.000 claims description 2
• WSVNXZBCYPWRCQ-UHFFFAOYSA-N 2-[[2-[[2-(4-fluorophenyl)phenyl]methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=CC=C1C1=CC=C(F)C=C1 WSVNXZBCYPWRCQ-UHFFFAOYSA-N 0.000 claims description 2
• UDOJUYSSRYDBNP-UHFFFAOYSA-N 2-[[2-[[4-(2,6-difluoropyridin-4-yl)phenyl]methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=C(C=2C=C(F)N=C(F)C=2)C=C1 UDOJUYSSRYDBNP-UHFFFAOYSA-N 0.000 claims description 2
• NQGJCFFOVIOINF-UHFFFAOYSA-N 2-[[4-hydroxy-3-(1H-indol-3-yl)-6-oxo-1H-pyridazine-5-carbonyl]amino]acetic acid Chemical compound N1C(=O)C(C(=O)NCC(=O)O)=C(O)C(C=2C3=CC=CC=C3NC=2)=N1 NQGJCFFOVIOINF-UHFFFAOYSA-N 0.000 claims description 2
• AHVSZWUPCCNAOZ-UHFFFAOYSA-N 2-[[5-hydroxy-2-[[2-(2-methoxyphenyl)phenyl]methyl]-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound COC1=CC=CC=C1C1=CC=CC=C1CN1C(=O)C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=N1 AHVSZWUPCCNAOZ-UHFFFAOYSA-N 0.000 claims description 2
• USQQRSHNDHDDAD-UHFFFAOYSA-N 2-[[5-hydroxy-3-oxo-2-[[3-(2-piperazin-1-ylpyridin-4-yl)phenyl]methyl]-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=CC(C=2C=C(N=CC=2)N2CCNCC2)=C1 USQQRSHNDHDDAD-UHFFFAOYSA-N 0.000 claims description 2
• JWXMUUZCFGXCRK-UHFFFAOYSA-N 2-[[5-hydroxy-3-oxo-2-[[4-(2-piperazin-1-ylpyridin-4-yl)phenyl]methyl]-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=C(C=2C=C(N=CC=2)N2CCNCC2)C=C1 JWXMUUZCFGXCRK-UHFFFAOYSA-N 0.000 claims description 2
• FIQFORZVCULREV-UHFFFAOYSA-N 2-[[5-hydroxy-3-oxo-6-propan-2-yl-2-(2,2,2-trifluoroethyl)pyridazine-4-carbonyl]amino]acetic acid Chemical compound CC(C)C1=NN(CC(F)(F)F)C(=O)C(C(=O)NCC(O)=O)=C1O FIQFORZVCULREV-UHFFFAOYSA-N 0.000 claims description 2
• ZHIDTPLDXKHNAO-UHFFFAOYSA-N 4-[2-[[5-(carboxymethylcarbamoyl)-4-hydroxy-6-oxo-3-propan-2-ylpyridazin-1-yl]methyl]phenyl]benzoic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=CC=C1C1=CC=C(C(O)=O)C=C1 ZHIDTPLDXKHNAO-UHFFFAOYSA-N 0.000 claims description 2
• 125000006281 4-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)C([H])([H])* 0.000 claims description 2
• 206010028980 Neoplasm Diseases 0.000 claims description 2
• 201000011510 cancer Diseases 0.000 claims description 2
• 238000002512 chemotherapy Methods 0.000 claims description 2
• 208000017169 kidney disease Diseases 0.000 claims description 2
• VPFOQJUBBWBKME-UHFFFAOYSA-N 2-[[5-hydroxy-3-oxo-6-propan-2-yl-2-[[2-(trifluoromethyl)phenyl]methyl]pyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=CC=C1C(F)(F)F VPFOQJUBBWBKME-UHFFFAOYSA-N 0.000 claims 3
• FSRJQICLTPDNNW-UHFFFAOYSA-N 2-[(2,6-dicyclohexyl-5-hydroxy-3-oxopyridazine-4-carbonyl)amino]acetic acid Chemical compound O=C1C(C(=O)NCC(=O)O)=C(O)C(C2CCCCC2)=NN1C1CCCCC1 FSRJQICLTPDNNW-UHFFFAOYSA-N 0.000 claims 1
• DWRGIUZLXHTJKW-UHFFFAOYSA-N 2-[(2-benzyl-5-hydroxy-3-oxo-6-phenylpyridazine-4-carbonyl)amino]acetic acid Chemical compound O=C1C(C(=O)NCC(=O)O)=C(O)C(C=2C=CC=CC=2)=NN1CC1=CC=CC=C1 DWRGIUZLXHTJKW-UHFFFAOYSA-N 0.000 claims 1
• MTJZXXIGRIUJEU-UHFFFAOYSA-N 2-[(2-benzyl-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carbonyl)amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=CC=C1 MTJZXXIGRIUJEU-UHFFFAOYSA-N 0.000 claims 1
• RTRPUIOGIULCPA-UHFFFAOYSA-N 2-[(2-benzyl-5-hydroxy-6-methyl-3-oxopyridazine-4-carbonyl)amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C)=NN1CC1=CC=CC=C1 RTRPUIOGIULCPA-UHFFFAOYSA-N 0.000 claims 1
• CYTOEKGIWACJBC-UHFFFAOYSA-N 2-[(2-benzyl-6-cyclohexyl-5-hydroxy-3-oxopyridazine-4-carbonyl)amino]acetic acid Chemical compound O=C1C(C(=O)NCC(=O)O)=C(O)C(C2CCCCC2)=NN1CC1=CC=CC=C1 CYTOEKGIWACJBC-UHFFFAOYSA-N 0.000 claims 1
• YIHUTURCVOVYCS-UHFFFAOYSA-N 2-[(2-cyclohexyl-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carbonyl)amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1C1CCCCC1 YIHUTURCVOVYCS-UHFFFAOYSA-N 0.000 claims 1
• VMQYMEKAPSRKMX-UHFFFAOYSA-N 2-[(4-hydroxy-6-oxo-3-phenyl-1h-pyridazine-5-carbonyl)amino]acetic acid Chemical compound N1C(=O)C(C(=O)NCC(=O)O)=C(O)C(C=2C=CC=CC=2)=N1 VMQYMEKAPSRKMX-UHFFFAOYSA-N 0.000 claims 1
• WRENSAXIPQHRGH-UHFFFAOYSA-N 2-[(6-tert-butyl-2-cyclohexyl-5-hydroxy-3-oxopyridazine-4-carbonyl)amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)(C)C)=NN1C1CCCCC1 WRENSAXIPQHRGH-UHFFFAOYSA-N 0.000 claims 1
• JSKPGEWZEVXBIQ-UHFFFAOYSA-N 2-[[2-(1,3-benzothiazol-2-ylmethyl)-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=NC2=CC=CC=C2S1 JSKPGEWZEVXBIQ-UHFFFAOYSA-N 0.000 claims 1
• FNSMXFOXZPNJEP-UHFFFAOYSA-N 2-[[2-(2-cyclopropylethyl)-5-hydroxy-3-oxo-6-phenylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(=O)O)=C(O)C(C=2C=CC=CC=2)=NN1CCC1CC1 FNSMXFOXZPNJEP-UHFFFAOYSA-N 0.000 claims 1
• OAQITUIZGBKVMW-UHFFFAOYSA-N 2-[[2-(2-cyclopropylethyl)-6-(4-fluorophenyl)-5-hydroxy-3-oxopyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(=O)O)=C(O)C(C=2C=CC(F)=CC=2)=NN1CCC1CC1 OAQITUIZGBKVMW-UHFFFAOYSA-N 0.000 claims 1
• VATJURRVWIQIFS-UHFFFAOYSA-N 2-[[2-[(2,3-dichlorophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=CC(Cl)=C1Cl VATJURRVWIQIFS-UHFFFAOYSA-N 0.000 claims 1
• RIBZNDZJFDETRR-UHFFFAOYSA-N 2-[[2-[(2,4-dichlorophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=C(Cl)C=C1Cl RIBZNDZJFDETRR-UHFFFAOYSA-N 0.000 claims 1
• WXFLMBUHZVVLLF-UHFFFAOYSA-N 2-[[2-[(2,4-difluorophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=C(F)C=C1F WXFLMBUHZVVLLF-UHFFFAOYSA-N 0.000 claims 1
• UPUDUHZONJHELB-UHFFFAOYSA-N 2-[[2-[(2,5-dichlorophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC(Cl)=CC=C1Cl UPUDUHZONJHELB-UHFFFAOYSA-N 0.000 claims 1
• UQNTWXHNXDNIIM-UHFFFAOYSA-N 2-[[2-[(2,5-difluorophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC(F)=CC=C1F UQNTWXHNXDNIIM-UHFFFAOYSA-N 0.000 claims 1
• XOXTVUWGCFOAAS-UHFFFAOYSA-N 2-[[2-[(2,6-dichlorophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=C(Cl)C=CC=C1Cl XOXTVUWGCFOAAS-UHFFFAOYSA-N 0.000 claims 1
• DPECEEYIAVHSFA-UHFFFAOYSA-N 2-[[2-[(2-bromophenyl)methyl]-6-tert-butyl-5-hydroxy-3-oxopyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)(C)C)=NN1CC1=CC=CC=C1Br DPECEEYIAVHSFA-UHFFFAOYSA-N 0.000 claims 1
• CEPMEUXTVODSRT-UHFFFAOYSA-N 2-[[2-[(2-chlorophenyl)methyl]-5-hydroxy-3-oxo-6-phenylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(=O)O)=C(O)C(C=2C=CC=CC=2)=NN1CC1=CC=CC=C1Cl CEPMEUXTVODSRT-UHFFFAOYSA-N 0.000 claims 1
• CVNGAKQDKQVZRD-UHFFFAOYSA-N 2-[[2-[(2-chlorophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=CC=C1Cl CVNGAKQDKQVZRD-UHFFFAOYSA-N 0.000 claims 1
• NFYPEYAMAKLRIX-UHFFFAOYSA-N 2-[[2-[(2-chlorophenyl)methyl]-5-hydroxy-6-(2-methoxyphenyl)-3-oxopyridazine-4-carbonyl]amino]acetic acid Chemical compound COC1=CC=CC=C1C(C(=C(C(=O)NCC(O)=O)C1=O)O)=NN1CC1=CC=CC=C1Cl NFYPEYAMAKLRIX-UHFFFAOYSA-N 0.000 claims 1
• ZBGRVTLAEJZBDF-UHFFFAOYSA-N 2-[[2-[(2-chlorophenyl)methyl]-5-hydroxy-6-(3-methoxyphenyl)-3-oxopyridazine-4-carbonyl]amino]acetic acid Chemical compound COC1=CC=CC(C=2C(=C(C(=O)NCC(O)=O)C(=O)N(CC=3C(=CC=CC=3)Cl)N=2)O)=C1 ZBGRVTLAEJZBDF-UHFFFAOYSA-N 0.000 claims 1
• YRXKJIUJOBYNPS-UHFFFAOYSA-N 2-[[2-[(2-chlorophenyl)methyl]-5-hydroxy-6-(4-methoxyphenyl)-3-oxopyridazine-4-carbonyl]amino]acetic acid Chemical compound C1=CC(OC)=CC=C1C(C(=C(C(=O)NCC(O)=O)C1=O)O)=NN1CC1=CC=CC=C1Cl YRXKJIUJOBYNPS-UHFFFAOYSA-N 0.000 claims 1
• HXTBLOTWPWBPDA-UHFFFAOYSA-N 2-[[2-[(2-chlorophenyl)methyl]-6-(3,5-difluorophenyl)-5-hydroxy-3-oxopyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(=O)O)=C(O)C(C=2C=C(F)C=C(F)C=2)=NN1CC1=CC=CC=C1Cl HXTBLOTWPWBPDA-UHFFFAOYSA-N 0.000 claims 1
• QALMZSSAQWCPGY-UHFFFAOYSA-N 2-[[2-[(2-chlorophenyl)methyl]-6-(3-ethoxy-5-fluorophenyl)-5-hydroxy-3-oxopyridazine-4-carbonyl]amino]acetic acid Chemical compound CCOC1=CC(F)=CC(C=2C(=C(C(=O)NCC(O)=O)C(=O)N(CC=3C(=CC=CC=3)Cl)N=2)O)=C1 QALMZSSAQWCPGY-UHFFFAOYSA-N 0.000 claims 1
• CQXIPEGUONYWOK-UHFFFAOYSA-N 2-[[2-[(2-chlorophenyl)methyl]-6-(4-fluorophenyl)-5-hydroxy-3-oxopyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(=O)O)=C(O)C(C=2C=CC(F)=CC=2)=NN1CC1=CC=CC=C1Cl CQXIPEGUONYWOK-UHFFFAOYSA-N 0.000 claims 1
• KDXBFIQIWOGQMC-UHFFFAOYSA-N 2-[[2-[(2-chlorophenyl)methyl]-6-cyclohexyl-5-hydroxy-3-oxopyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(=O)O)=C(O)C(C2CCCCC2)=NN1CC1=CC=CC=C1Cl KDXBFIQIWOGQMC-UHFFFAOYSA-N 0.000 claims 1
• UCPFRQPQNFCCNE-UHFFFAOYSA-N 2-[[2-[(2-chlorophenyl)methyl]-6-ethoxycarbonyl-5-hydroxy-3-oxopyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(=O)OCC)=NN1CC1=CC=CC=C1Cl UCPFRQPQNFCCNE-UHFFFAOYSA-N 0.000 claims 1
• QPJVOFPLYJJKLN-UHFFFAOYSA-N 2-[[2-[(2-fluoro-4-phenylphenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=C(C=2C=CC=CC=2)C=C1F QPJVOFPLYJJKLN-UHFFFAOYSA-N 0.000 claims 1
• ROWJQKRIMLNZTO-UHFFFAOYSA-N 2-[[2-[(2-fluoro-4-pyridin-4-ylphenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=C(C=2C=CN=CC=2)C=C1F ROWJQKRIMLNZTO-UHFFFAOYSA-N 0.000 claims 1
• HAWXRUHIBMESDD-UHFFFAOYSA-N 2-[[2-[(2-fluorophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=CC=C1F HAWXRUHIBMESDD-UHFFFAOYSA-N 0.000 claims 1
• OSZRGJFOZFQCGY-UHFFFAOYSA-N 2-[[2-[(3,4-dichlorophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=C(Cl)C(Cl)=C1 OSZRGJFOZFQCGY-UHFFFAOYSA-N 0.000 claims 1
• GNYGLNZSICUEPB-UHFFFAOYSA-N 2-[[2-[(3,5-difluorophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC(F)=CC(F)=C1 GNYGLNZSICUEPB-UHFFFAOYSA-N 0.000 claims 1
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• HOFQOZPOIRYDEZ-UHFFFAOYSA-N 2-[[2-[[2-fluoro-4-(2-methoxyphenyl)phenyl]methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound COC1=CC=CC=C1C(C=C1F)=CC=C1CN1C(=O)C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=N1 HOFQOZPOIRYDEZ-UHFFFAOYSA-N 0.000 claims 1
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• QBYVUMGLQABSAD-UHFFFAOYSA-N 2-[[2-[[2-fluoro-4-(4-nitrophenyl)phenyl]methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=C(C=2C=CC(=CC=2)[N+]([O-])=O)C=C1F QBYVUMGLQABSAD-UHFFFAOYSA-N 0.000 claims 1
• SZKPZWMBMGCDDY-UHFFFAOYSA-N 2-[[2-[[2-fluoro-4-[4-(trifluoromethyl)phenyl]phenyl]methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=C(C=2C=CC(=CC=2)C(F)(F)F)C=C1F SZKPZWMBMGCDDY-UHFFFAOYSA-N 0.000 claims 1
• WEYGUQCGUQEXPD-UHFFFAOYSA-N 2-[[2-[[4-(4-fluorophenyl)phenyl]methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=C(C=2C=CC(F)=CC=2)C=C1 WEYGUQCGUQEXPD-UHFFFAOYSA-N 0.000 claims 1
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• PBPXHPGOPGLQCP-UHFFFAOYSA-N 2-[[5-hydroxy-2-[(2-nitrophenyl)methyl]-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=CC=C1[N+]([O-])=O PBPXHPGOPGLQCP-UHFFFAOYSA-N 0.000 claims 1
• HCDAUFAKGYNIRH-UHFFFAOYSA-N 2-[[5-hydroxy-2-[[3-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]phenyl]methyl]-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=CC(C=2C=NC(=CC=2)N2CCN(C)CC2)=C1 HCDAUFAKGYNIRH-UHFFFAOYSA-N 0.000 claims 1
• ZVPVOVAZTUWNQD-UHFFFAOYSA-N 2-[[5-hydroxy-2-[[4-(2-methoxyphenyl)phenyl]methyl]-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound COC1=CC=CC=C1C(C=C1)=CC=C1CN1C(=O)C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=N1 ZVPVOVAZTUWNQD-UHFFFAOYSA-N 0.000 claims 1
• NLEDBOJPZUGKKW-UHFFFAOYSA-N 2-[[5-hydroxy-2-[[4-(2-methoxypyridin-4-yl)phenyl]methyl]-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound C1=NC(OC)=CC(C=2C=CC(CN3C(C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=N3)=O)=CC=2)=C1 NLEDBOJPZUGKKW-UHFFFAOYSA-N 0.000 claims 1
• HEWKEZWYAMOPPW-UHFFFAOYSA-N 2-[[5-hydroxy-2-[[4-(4-nitrophenyl)phenyl]methyl]-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=C(C=2C=CC(=CC=2)[N+]([O-])=O)C=C1 HEWKEZWYAMOPPW-UHFFFAOYSA-N 0.000 claims 1
• YACWBZCPKGSXSL-UHFFFAOYSA-N 2-[[5-hydroxy-2-[[4-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]phenyl]methyl]-3-oxo-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=C(C=2C=NC(=CC=2)N2CCN(C)CC2)C=C1 YACWBZCPKGSXSL-UHFFFAOYSA-N 0.000 claims 1
• RWILEBQJSWJTJX-UHFFFAOYSA-N 2-[[5-hydroxy-3-oxo-2-[(2-phenylphenyl)methyl]-6-propan-2-ylpyridazine-4-carbonyl]amino]acetic acid Chemical compound O=C1C(C(=O)NCC(O)=O)=C(O)C(C(C)C)=NN1CC1=CC=CC=C1C1=CC=CC=C1 RWILEBQJSWJTJX-UHFFFAOYSA-N 0.000 claims 1
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