JP5313925B2 - Ｎ置換グリシン誘導体：ヒドロキシラーゼ阻害剤 - Google Patents

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Publication number

JP5313925B2

JP5313925B2 JP2009545699A JP2009545699A JP5313925B2 JP 5313925 B2 JP5313925 B2 JP 5313925B2 JP 2009545699 A JP2009545699 A JP 2009545699A JP 2009545699 A JP2009545699 A JP 2009545699A JP 5313925 B2 JP5313925 B2 JP 5313925B2

Authority

JP

Japan

Prior art keywords

mmol

added

oxo

hydroxy

dihydro

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 3
• 150000002332 glycine derivatives Chemical class 0.000 title abstract description 3
• 229940122439 Hydroxylase inhibitor Drugs 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims description 404
• -1 2-fluoro-4-bromobenzyl Chemical group 0.000 claims description 157
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 54
• 150000003839 salts Chemical class 0.000 claims description 32
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 12
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
• 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 4
• 125000005059 halophenyl group Chemical group 0.000 claims description 4
• 125000006281 4-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)C([H])([H])* 0.000 claims description 2
• 125000005036 alkoxyphenyl group Chemical group 0.000 claims 1
• 108010043005 Prolyl Hydroxylases Proteins 0.000 abstract description 13
• 102000004079 Prolyl Hydroxylases Human genes 0.000 abstract description 13
• 208000007502 anemia Diseases 0.000 abstract description 11
• 230000005764 inhibitory process Effects 0.000 abstract description 8
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 7
• 102000004190 Enzymes Human genes 0.000 abstract description 6
• 108090000790 Enzymes Proteins 0.000 abstract description 6
• 201000010099 disease Diseases 0.000 abstract description 4
• 239000005557 antagonist Substances 0.000 abstract 1
• MYKHANQTTIRZJK-UHFFFAOYSA-N pyridazine-3,4-dione Chemical compound O=C1C=CN=NC1=O MYKHANQTTIRZJK-UHFFFAOYSA-N 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 584
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 384
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 361
• 238000006243 chemical reaction Methods 0.000 description 311
• 239000000243 solution Substances 0.000 description 290
• 235000019439 ethyl acetate Nutrition 0.000 description 256
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 248
• 239000000047 product Substances 0.000 description 219
• 238000005160 1H NMR spectroscopy Methods 0.000 description 203
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 174
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 166
• 239000000203 mixture Substances 0.000 description 134
• 239000007787 solid Substances 0.000 description 129
• 239000004471 Glycine Substances 0.000 description 126
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 123
• 239000010410 layer Substances 0.000 description 120
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 105
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 102
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 95
• 239000012267 brine Substances 0.000 description 92
• 238000010992 reflux Methods 0.000 description 92
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 92
• 239000012044 organic layer Substances 0.000 description 83
• WUWHFEHKUQVYLF-UHFFFAOYSA-M sodium;2-aminoacetate Chemical compound [Na+].NCC([O-])=O WUWHFEHKUQVYLF-UHFFFAOYSA-M 0.000 description 80
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 78
• XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 76
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 75
• 229910004298 SiO 2 Inorganic materials 0.000 description 73
• 238000004440 column chromatography Methods 0.000 description 73
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 70
• 229910000104 sodium hydride Inorganic materials 0.000 description 63
• 239000012312 sodium hydride Substances 0.000 description 62
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 61
• 239000002904 solvent Substances 0.000 description 57
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 55
• 230000002829 reductive effect Effects 0.000 description 55
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 52
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 52
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 50
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 48
• XGCDBGRZEKYHNV-UHFFFAOYSA-N 1,1-bis(diphenylphosphino)methane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CP(C=1C=CC=CC=1)C1=CC=CC=C1 XGCDBGRZEKYHNV-UHFFFAOYSA-N 0.000 description 45
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 43
• 125000000217 alkyl group Chemical group 0.000 description 41
• 239000000843 powder Substances 0.000 description 41
• 239000011541 reaction mixture Substances 0.000 description 41
• 125000001072 heteroaryl group Chemical group 0.000 description 37
• UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 description 36
• GQHTUMJGOHRCHB-UHFFFAOYSA-N DBU Substances C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 34
• 238000004128 high performance liquid chromatography Methods 0.000 description 34
• 239000000377 silicon dioxide Substances 0.000 description 33
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 32
• 125000003118 aryl group Chemical group 0.000 description 32
• 238000004587 chromatography analysis Methods 0.000 description 31
• 235000002639 sodium chloride Nutrition 0.000 description 31
• 229910052757 nitrogen Inorganic materials 0.000 description 30
• 125000000592 heterocycloalkyl group Chemical group 0.000 description 28
• 239000000741 silica gel Substances 0.000 description 28
• 229910002027 silica gel Inorganic materials 0.000 description 28
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 27
• 229910000027 potassium carbonate Inorganic materials 0.000 description 26
• 229910052739 hydrogen Inorganic materials 0.000 description 24
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 24
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 22
• 239000008346 aqueous phase Substances 0.000 description 21
• 239000000284 extract Substances 0.000 description 21
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
• 239000003921 oil Substances 0.000 description 20
• 238000003756 stirring Methods 0.000 description 20
• 239000000725 suspension Substances 0.000 description 20
• 238000000034 method Methods 0.000 description 19
• 235000019198 oils Nutrition 0.000 description 19
• 239000012074 organic phase Substances 0.000 description 19
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
• 239000000706 filtrate Substances 0.000 description 18
• 239000002244 precipitate Substances 0.000 description 17
• 239000010779 crude oil Substances 0.000 description 15
• 238000001914 filtration Methods 0.000 description 15
• 239000001257 hydrogen Substances 0.000 description 15
• 239000007864 aqueous solution Substances 0.000 description 14
• 239000008194 pharmaceutical composition Substances 0.000 description 14
• 239000012258 stirred mixture Substances 0.000 description 14
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 13
• PURSZYWBIQIANP-UHFFFAOYSA-N 1-(bromomethyl)-2-chlorobenzene Chemical compound ClC1=CC=CC=C1CBr PURSZYWBIQIANP-UHFFFAOYSA-N 0.000 description 13
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 13
• 125000002877 alkyl aryl group Chemical group 0.000 description 13
• 150000002431 hydrogen Chemical class 0.000 description 13
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
• 235000019341 magnesium sulphate Nutrition 0.000 description 13
• 125000006374 C2-C10 alkenyl group Chemical group 0.000 description 12
• 125000005865 C2-C10alkynyl group Chemical group 0.000 description 12
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
• 238000001953 recrystallisation Methods 0.000 description 12
• 239000012453 solvate Substances 0.000 description 12
• 239000003054 catalyst Substances 0.000 description 11
• 229910052760 oxygen Inorganic materials 0.000 description 11
• 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 10
• 229960000583 acetic acid Drugs 0.000 description 10
• 239000002253 acid Substances 0.000 description 10
• 210000004027 cell Anatomy 0.000 description 10
• GGIYCALCWUWLHT-UHFFFAOYSA-N n-(3-chloro-2-methylphenyl)-4,5-dihydro-1,3-thiazol-2-amine Chemical compound CC1=C(Cl)C=CC=C1NC1=NCCS1 GGIYCALCWUWLHT-UHFFFAOYSA-N 0.000 description 10
• IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 10
• 125000000081 (C5-C8) cycloalkenyl group Chemical group 0.000 description 9
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 9
• 238000003818 flash chromatography Methods 0.000 description 9
• 239000012299 nitrogen atmosphere Substances 0.000 description 9
• 238000001556 precipitation Methods 0.000 description 9
• 238000002390 rotary evaporation Methods 0.000 description 9
• 125000001424 substituent group Chemical group 0.000 description 9
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 8
• 125000005213 alkyl heteroaryl group Chemical group 0.000 description 8
• 125000004432 carbon atom Chemical group C* 0.000 description 8
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
• 150000007857 hydrazones Chemical class 0.000 description 8
• 238000004519 manufacturing process Methods 0.000 description 8
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 8
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 7
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 7
• 206010021143 Hypoxia Diseases 0.000 description 7
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• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 6
• SCZNXLWKYFICFV-UHFFFAOYSA-N 1,2,3,4,5,7,8,9-octahydropyrido[1,2-b]diazepine Chemical compound C1CCCNN2CCCC=C21 SCZNXLWKYFICFV-UHFFFAOYSA-N 0.000 description 6
• TXVVVEUSVBLDED-UHFFFAOYSA-N 1-(bromomethyl)-2-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1CBr TXVVVEUSVBLDED-UHFFFAOYSA-N 0.000 description 6
• QZNQSIHCDAGZIA-UHFFFAOYSA-N 1-(bromomethyl)-4-tert-butylbenzene Chemical compound CC(C)(C)C1=CC=C(CBr)C=C1 QZNQSIHCDAGZIA-UHFFFAOYSA-N 0.000 description 6
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 6
• 101000881678 Homo sapiens Prolyl hydroxylase EGLN3 Proteins 0.000 description 6
• 102100037247 Prolyl hydroxylase EGLN3 Human genes 0.000 description 6
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
• 125000003342 alkenyl group Chemical group 0.000 description 6
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• KVSVNRFSKRFPIL-UHFFFAOYSA-N 1-(bromomethyl)-3,5-difluorobenzene Chemical compound FC1=CC(F)=CC(CBr)=C1 KVSVNRFSKRFPIL-UHFFFAOYSA-N 0.000 description 5
• 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 description 5
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• NSFJAFZHYOAMHL-UHFFFAOYSA-N (4-nitrophenyl)boronic acid Chemical compound OB(O)C1=CC=C([N+]([O-])=O)C=C1 NSFJAFZHYOAMHL-UHFFFAOYSA-N 0.000 description 4
• 0 *C(*NC(C(C(N(*)N=C1*)=O)=C1O)=O)=O Chemical compound *C(*NC(C(C(N(*)N=C1*)=O)=C1O)=O)=O 0.000 description 4
• HZQLUIZFUXNFHK-UHFFFAOYSA-N 1-(bromomethyl)-4-phenylbenzene Chemical group C1=CC(CBr)=CC=C1C1=CC=CC=C1 HZQLUIZFUXNFHK-UHFFFAOYSA-N 0.000 description 4
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 4
• 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 4
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
• 102000003951 Erythropoietin Human genes 0.000 description 4
• 108090000394 Erythropoietin Proteins 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
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
• 239000004480 active ingredient Substances 0.000 description 4
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• 238000000576 coating method Methods 0.000 description 4
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• 125000004093 cyano group Chemical group *C#N 0.000 description 4
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• 125000000524 functional group Chemical group 0.000 description 4
• 229910052736 halogen Inorganic materials 0.000 description 4
• 150000002367 halogens Chemical class 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
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
• KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 4
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 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 description 4
• 238000012360 testing method Methods 0.000 description 4
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
• 238000010792 warming Methods 0.000 description 4
• ROEQGIFOWRQYHD-UHFFFAOYSA-N (2-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC=C1B(O)O ROEQGIFOWRQYHD-UHFFFAOYSA-N 0.000 description 3
• LOZSSHYLDBDYSQ-UHFFFAOYSA-N 1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]piperazine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=NC(N2CCNCC2)=C1 LOZSSHYLDBDYSQ-UHFFFAOYSA-N 0.000 description 3
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 3
• 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 description 3
• 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 description 3
• ROFGRXZLIAMOFL-UHFFFAOYSA-N 2-[[2-[(3-cyanophenyl)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(C#N)=C1 ROFGRXZLIAMOFL-UHFFFAOYSA-N 0.000 description 3
• 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 description 3
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• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• 239000012153 distilled water Substances 0.000 description 1
• CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
• POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000007920 enema Substances 0.000 description 1
• 229940079360 enema for constipation Drugs 0.000 description 1
• 239000003623 enhancer Substances 0.000 description 1
• 230000002708 enhancing effect Effects 0.000 description 1
• 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 1
• 150000002170 ethers Chemical class 0.000 description 1
• 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 description 1
• PQTGSSMVZPQHTN-UHFFFAOYSA-N ethyl 2-(1,3-benzothiazol-2-ylmethyl)-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C(C)C)=NN1CC1=NC2=CC=CC=C2S1 PQTGSSMVZPQHTN-UHFFFAOYSA-N 0.000 description 1
• KJZRFVYVKDZBHT-UHFFFAOYSA-N ethyl 2-(2-cyclohexylethyl)-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C(C)C)=NN1CCC1CCCCC1 KJZRFVYVKDZBHT-UHFFFAOYSA-N 0.000 description 1
• GFZVJNYHDPDRBS-UHFFFAOYSA-N ethyl 2-(2-cyclopropylethyl)-5-hydroxy-3-oxo-6-phenylpyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C=2C=CC=CC=2)=NN1CCC1CC1 GFZVJNYHDPDRBS-UHFFFAOYSA-N 0.000 description 1
• DNRUIQVIEDGXJH-UHFFFAOYSA-N ethyl 2-(2-cyclopropylethyl)-6-(4-fluorophenyl)-5-hydroxy-3-oxopyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C=2C=CC(F)=CC=2)=NN1CCC1CC1 DNRUIQVIEDGXJH-UHFFFAOYSA-N 0.000 description 1
• BXHARDVKQMJAEM-UHFFFAOYSA-N ethyl 2-(cyclohexylhydrazinylidene)-3,3-dimethylbutanoate Chemical compound CCOC(=O)C(C(C)(C)C)=NNC1CCCCC1 BXHARDVKQMJAEM-UHFFFAOYSA-N 0.000 description 1
• DJMKTEXQYZVXGI-UHFFFAOYSA-N ethyl 2-(cyclohexylhydrazinylidene)-3-methylbutanoate Chemical compound CCOC(=O)C(C(C)C)=NNC1CCCCC1 DJMKTEXQYZVXGI-UHFFFAOYSA-N 0.000 description 1
• RILAPGUOLBUFTK-UHFFFAOYSA-N ethyl 2-[(2,3-dichlorophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C(C)C)=NN1CC1=CC=CC(Cl)=C1Cl RILAPGUOLBUFTK-UHFFFAOYSA-N 0.000 description 1
• BIGUQIKFECWKQO-UHFFFAOYSA-N ethyl 2-[(2,4-dichlorophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C(C)C)=NN1CC1=CC=C(Cl)C=C1Cl BIGUQIKFECWKQO-UHFFFAOYSA-N 0.000 description 1
• IDBQEZDRIXAHIK-UHFFFAOYSA-N ethyl 2-[(2,4-difluorophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C(C)C)=NN1CC1=CC=C(F)C=C1F IDBQEZDRIXAHIK-UHFFFAOYSA-N 0.000 description 1
• AKSDIRUPAFAJOD-UHFFFAOYSA-N ethyl 2-[(2,5-dichlorophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C(C)C)=NN1CC1=CC(Cl)=CC=C1Cl AKSDIRUPAFAJOD-UHFFFAOYSA-N 0.000 description 1
• NMUXZVIBAUYGBH-UHFFFAOYSA-N ethyl 2-[(2,5-difluorophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C(C)C)=NN1CC1=CC(F)=CC=C1F NMUXZVIBAUYGBH-UHFFFAOYSA-N 0.000 description 1
• BEKIJTINZPSVME-UHFFFAOYSA-N ethyl 2-[(2,6-dichlorophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C(C)C)=NN1CC1=C(Cl)C=CC=C1Cl BEKIJTINZPSVME-UHFFFAOYSA-N 0.000 description 1
• OBBCUYSNSIRXPX-UHFFFAOYSA-N ethyl 2-[(2-bromophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C(C)C)=NN1CC1=CC=CC=C1Br OBBCUYSNSIRXPX-UHFFFAOYSA-N 0.000 description 1
• NWJVJYVPSJGWEY-UHFFFAOYSA-N ethyl 2-[(2-bromophenyl)methyl]-6-tert-butyl-5-hydroxy-3-oxopyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C(C)(C)C)=NN1CC1=CC=CC=C1Br NWJVJYVPSJGWEY-UHFFFAOYSA-N 0.000 description 1
• ALDQLNUNBAAUNX-UHFFFAOYSA-N ethyl 2-[(2-chlorophenyl)methyl]-5-hydroxy-3-oxo-6-phenylpyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C=2C=CC=CC=2)=NN1CC1=CC=CC=C1Cl ALDQLNUNBAAUNX-UHFFFAOYSA-N 0.000 description 1
• SKNPLGQCOHFBLA-UHFFFAOYSA-N ethyl 2-[(2-chlorophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C(C)C)=NN1CC1=CC=CC=C1Cl SKNPLGQCOHFBLA-UHFFFAOYSA-N 0.000 description 1
• FOOBXZCSIKNPRJ-UHFFFAOYSA-N ethyl 2-[(2-chlorophenyl)methyl]-5-hydroxy-6-(2-methoxyphenyl)-3-oxopyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C=2C(=CC=CC=2)OC)=NN1CC1=CC=CC=C1Cl FOOBXZCSIKNPRJ-UHFFFAOYSA-N 0.000 description 1
• LVVIHGFOFSQTBA-UHFFFAOYSA-N ethyl 2-[(2-chlorophenyl)methyl]-5-hydroxy-6-(3-methoxyphenyl)-3-oxopyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C=2C=C(OC)C=CC=2)=NN1CC1=CC=CC=C1Cl LVVIHGFOFSQTBA-UHFFFAOYSA-N 0.000 description 1
• WZUZYFJRHCMZPT-UHFFFAOYSA-N ethyl 2-[(2-chlorophenyl)methyl]-5-hydroxy-6-(4-methoxyphenyl)-3-oxopyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C=2C=CC(OC)=CC=2)=NN1CC1=CC=CC=C1Cl WZUZYFJRHCMZPT-UHFFFAOYSA-N 0.000 description 1
• MISMZBNWTCKWKN-UHFFFAOYSA-N ethyl 2-[(2-chlorophenyl)methyl]-6-(3,5-difluorophenyl)-5-hydroxy-3-oxopyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C=2C=C(F)C=C(F)C=2)=NN1CC1=CC=CC=C1Cl MISMZBNWTCKWKN-UHFFFAOYSA-N 0.000 description 1
• FAKJYTIJYVYXHC-UHFFFAOYSA-N ethyl 2-[(2-chlorophenyl)methyl]-6-(3-ethoxy-5-fluorophenyl)-5-hydroxy-3-oxopyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C=2C=C(OCC)C=C(F)C=2)=NN1CC1=CC=CC=C1Cl FAKJYTIJYVYXHC-UHFFFAOYSA-N 0.000 description 1
• RTOLSFNTBSHEPQ-UHFFFAOYSA-N ethyl 2-[(2-chlorophenyl)methyl]-6-(4-fluorophenyl)-5-hydroxy-3-oxopyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C=2C=CC(F)=CC=2)=NN1CC1=CC=CC=C1Cl RTOLSFNTBSHEPQ-UHFFFAOYSA-N 0.000 description 1
• YGSVNVYMLFUZJQ-UHFFFAOYSA-N ethyl 2-[(2-chlorophenyl)methyl]-6-cyclohexyl-5-hydroxy-3-oxopyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C2CCCCC2)=NN1CC1=CC=CC=C1Cl YGSVNVYMLFUZJQ-UHFFFAOYSA-N 0.000 description 1
• FNUZXSFHLXICNL-UHFFFAOYSA-N ethyl 2-[(2-fluorophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C(C)C)=NN1CC1=CC=CC=C1F FNUZXSFHLXICNL-UHFFFAOYSA-N 0.000 description 1
• OYVYWSQDTPNXEC-UHFFFAOYSA-N ethyl 2-[(3,4-dichlorophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C(C)C)=NN1CC1=CC=C(Cl)C(Cl)=C1 OYVYWSQDTPNXEC-UHFFFAOYSA-N 0.000 description 1
• LEJBYZXKJRAFLQ-UHFFFAOYSA-N ethyl 2-[(3,5-difluorophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C(C)C)=NN1CC1=CC(F)=CC(F)=C1 LEJBYZXKJRAFLQ-UHFFFAOYSA-N 0.000 description 1
• OXPCSLROEHKMBN-UHFFFAOYSA-N ethyl 2-[(3,5-difluorophenyl)methyl]-5-hydroxy-6-(4-methoxyphenyl)-3-oxopyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C=2C=CC(OC)=CC=2)=NN1CC1=CC(F)=CC(F)=C1 OXPCSLROEHKMBN-UHFFFAOYSA-N 0.000 description 1
• NYTKTLRAJUOELI-UHFFFAOYSA-N ethyl 2-[(3-bromophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C(C)C)=NN1CC1=CC=CC(Br)=C1 NYTKTLRAJUOELI-UHFFFAOYSA-N 0.000 description 1
• GMGUMMRHVSGWLR-UHFFFAOYSA-N ethyl 2-[(3-cyanophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C(C)C)=NN1CC1=CC=CC(C#N)=C1 GMGUMMRHVSGWLR-UHFFFAOYSA-N 0.000 description 1
• DSKKWVHOHKLORP-UHFFFAOYSA-N ethyl 2-[(3-ethoxy-3-oxopropanoyl)hydrazinylidene]-3,3-dimethylbutanoate Chemical compound CCOC(=O)CC(=O)NN=C(C(C)(C)C)C(=O)OCC DSKKWVHOHKLORP-UHFFFAOYSA-N 0.000 description 1
• IBBLCTUORFZRCO-UHFFFAOYSA-N ethyl 2-[(4-bromo-2-fluorophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C(C)C)=NN1CC1=CC=C(Br)C=C1F IBBLCTUORFZRCO-UHFFFAOYSA-N 0.000 description 1
• SBEOSNPMUSUGTP-UHFFFAOYSA-N ethyl 2-[(4-chloro-2-fluorophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C(C)C)=NN1CC1=CC=C(Cl)C=C1F SBEOSNPMUSUGTP-UHFFFAOYSA-N 0.000 description 1
• XHDFJUVTCOOEJU-UHFFFAOYSA-N ethyl 2-[(4-fluorophenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C(C)C)=NN1CC1=CC=C(F)C=C1 XHDFJUVTCOOEJU-UHFFFAOYSA-N 0.000 description 1
• VYIAZTBMFYMKHQ-UHFFFAOYSA-N ethyl 2-[(4-tert-butylphenyl)methyl]-5-hydroxy-3-oxo-6-phenylpyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C=2C=CC=CC=2)=NN1CC1=CC=C(C(C)(C)C)C=C1 VYIAZTBMFYMKHQ-UHFFFAOYSA-N 0.000 description 1
• WUHIIDQYZURKDY-UHFFFAOYSA-N ethyl 2-[(4-tert-butylphenyl)methyl]-5-hydroxy-3-oxo-6-propan-2-ylpyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C(C)C)=NN1CC1=CC=C(C(C)(C)C)C=C1 WUHIIDQYZURKDY-UHFFFAOYSA-N 0.000 description 1
• VGHLUOXKWDBQSY-UHFFFAOYSA-N ethyl 2-[(4-tert-butylphenyl)methyl]-6-(4-chlorophenyl)-5-hydroxy-3-oxopyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C=2C=CC(Cl)=CC=2)=NN1CC1=CC=C(C(C)(C)C)C=C1 VGHLUOXKWDBQSY-UHFFFAOYSA-N 0.000 description 1
• IFPBXJGIXOXNBM-UHFFFAOYSA-N ethyl 2-[(4-tert-butylphenyl)methyl]-6-cyclohexyl-5-hydroxy-3-oxopyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C2CCCCC2)=NN1CC1=CC=C(C(C)(C)C)C=C1 IFPBXJGIXOXNBM-UHFFFAOYSA-N 0.000 description 1
• CCZFSCAJHXPPPM-UHFFFAOYSA-N ethyl 2-benzyl-5-hydroxy-3-oxo-6-(trifluoromethyl)pyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C(F)(F)F)=NN1CC1=CC=CC=C1 CCZFSCAJHXPPPM-UHFFFAOYSA-N 0.000 description 1
• PNYREBFWYMKVQF-UHFFFAOYSA-N ethyl 2-benzyl-5-hydroxy-6-methyl-3-oxopyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C)=NN1CC1=CC=CC=C1 PNYREBFWYMKVQF-UHFFFAOYSA-N 0.000 description 1
• XEAUYKHVOSVDCF-UHFFFAOYSA-N ethyl 2-benzyl-6-cyclohexyl-5-hydroxy-3-oxopyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C2CCCCC2)=NN1CC1=CC=CC=C1 XEAUYKHVOSVDCF-UHFFFAOYSA-N 0.000 description 1
• MAOUXDYQHDQFFV-UHFFFAOYSA-N ethyl 2-cyclohexyl-2-oxoacetate Chemical compound CCOC(=O)C(=O)C1CCCCC1 MAOUXDYQHDQFFV-UHFFFAOYSA-N 0.000 description 1
• KJHQVUNUOIEYSV-UHFFFAOYSA-N ethyl 3,3,3-trifluoro-2-oxopropanoate Chemical compound CCOC(=O)C(=O)C(F)(F)F KJHQVUNUOIEYSV-UHFFFAOYSA-N 0.000 description 1
• JAPFKORQPACRJD-JXAWBTAJSA-N ethyl 3-[(2z)-2-[2-ethoxy-1-(4-fluorophenyl)-2-oxoethylidene]hydrazinyl]-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)N\N=C(/C(=O)OCC)C1=CC=C(F)C=C1 JAPFKORQPACRJD-JXAWBTAJSA-N 0.000 description 1
• RPIUKKGKWXYGNX-UHFFFAOYSA-N ethyl 3-[2-[1-(4-tert-butylphenyl)-2-ethoxy-2-oxoethylidene]hydrazinyl]-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)NN=C(C(=O)OCC)C1=CC=C(C(C)(C)C)C=C1 RPIUKKGKWXYGNX-UHFFFAOYSA-N 0.000 description 1
• CMMVOTXBVRTMGS-UHFFFAOYSA-N ethyl 3-[amino(benzyl)amino]-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)N(N)CC1=CC=CC=C1 CMMVOTXBVRTMGS-UHFFFAOYSA-N 0.000 description 1
• GOQQIBZDTDSGQA-UHFFFAOYSA-N ethyl 3-cyclohexyl-4-hydroxy-6-oxo-1h-pyridazine-5-carboxylate Chemical compound N1C(=O)C(C(=O)OCC)=C(O)C(C2CCCCC2)=N1 GOQQIBZDTDSGQA-UHFFFAOYSA-N 0.000 description 1
• VYSXDXSBJDMABJ-UHFFFAOYSA-N ethyl 4-hydroxy-3-(3-methoxyphenyl)-6-oxo-1h-pyridazine-5-carboxylate Chemical compound N1C(=O)C(C(=O)OCC)=C(O)C(C=2C=C(OC)C=CC=2)=N1 VYSXDXSBJDMABJ-UHFFFAOYSA-N 0.000 description 1
• QWMGBEFHRVZPBO-UHFFFAOYSA-N ethyl 4-hydroxy-3-(4-methoxyphenyl)-6-oxo-1h-pyridazine-5-carboxylate Chemical compound N1C(=O)C(C(=O)OCC)=C(O)C(C=2C=CC(OC)=CC=2)=N1 QWMGBEFHRVZPBO-UHFFFAOYSA-N 0.000 description 1
• PHNUTWFXHAUORG-UHFFFAOYSA-N ethyl 4-hydroxy-3-methyl-6-oxo-1h-pyridazine-5-carboxylate Chemical compound CCOC(=O)C1=C(O)C(C)=NNC1=O PHNUTWFXHAUORG-UHFFFAOYSA-N 0.000 description 1
• OVSVHYGXFUXPAI-UHFFFAOYSA-N ethyl 4-hydroxy-6-oxo-3-(trifluoromethyl)-1h-pyridazine-5-carboxylate Chemical compound CCOC(=O)C1=C(O)C(C(F)(F)F)=NNC1=O OVSVHYGXFUXPAI-UHFFFAOYSA-N 0.000 description 1
• UCQPLDQYPHTEMR-UHFFFAOYSA-N ethyl 4-hydroxy-6-oxo-3-propan-2-yl-1h-pyridazine-5-carboxylate Chemical compound CCOC(=O)C1=C(O)C(C(C)C)=NNC1=O UCQPLDQYPHTEMR-UHFFFAOYSA-N 0.000 description 1
• ZZLSPUMGEBANAF-UHFFFAOYSA-N ethyl 5-hydroxy-2-[(2-nitrophenyl)methyl]-3-oxo-6-propan-2-ylpyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C(C)C)=NN1CC1=CC=CC=C1[N+]([O-])=O ZZLSPUMGEBANAF-UHFFFAOYSA-N 0.000 description 1
• HACZFEPVNJUXQF-UHFFFAOYSA-N ethyl 5-hydroxy-3-oxo-2-[(2-phenylphenyl)methyl]-6-propan-2-ylpyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C(C)C)=NN1CC1=CC=CC=C1C1=CC=CC=C1 HACZFEPVNJUXQF-UHFFFAOYSA-N 0.000 description 1
• NDJSVYLEOSFDIJ-UHFFFAOYSA-N ethyl 5-hydroxy-3-oxo-2-[(3-phenylphenyl)methyl]-6-propan-2-ylpyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C(C)C)=NN1CC1=CC=CC(C=2C=CC=CC=2)=C1 NDJSVYLEOSFDIJ-UHFFFAOYSA-N 0.000 description 1
• PCCNKPUSFMKNFJ-UHFFFAOYSA-N ethyl 5-hydroxy-3-oxo-2-[(4-phenylphenyl)methyl]-6-propan-2-ylpyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C(C)C)=NN1CC1=CC=C(C=2C=CC=CC=2)C=C1 PCCNKPUSFMKNFJ-UHFFFAOYSA-N 0.000 description 1
• ZNTUPPLZBOCGNW-UHFFFAOYSA-N ethyl 5-hydroxy-3-oxo-6-phenyl-2-(2-phenylethyl)pyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C=2C=CC=CC=2)=NN1CCC1=CC=CC=C1 ZNTUPPLZBOCGNW-UHFFFAOYSA-N 0.000 description 1
• DOOAVVBBRJIHKQ-UHFFFAOYSA-N ethyl 5-hydroxy-3-oxo-6-propan-2-yl-2-[[2-(trifluoromethyl)phenyl]methyl]pyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C(C)C)=NN1CC1=CC=CC=C1C(F)(F)F DOOAVVBBRJIHKQ-UHFFFAOYSA-N 0.000 description 1
• ISJQRTRHEXYKRJ-UHFFFAOYSA-N ethyl 6-(3,5-difluorophenyl)-2-[(3,5-difluorophenyl)methyl]-5-hydroxy-3-oxopyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C=2C=C(F)C=C(F)C=2)=NN1CC1=CC(F)=CC(F)=C1 ISJQRTRHEXYKRJ-UHFFFAOYSA-N 0.000 description 1
• KHXIWILCHUCWGL-UHFFFAOYSA-N ethyl 6-(3,5-difluorophenyl)-5-hydroxy-3-oxo-2-[[2-(trifluoromethyl)phenyl]methyl]pyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C=2C=C(F)C=C(F)C=2)=NN1CC1=CC=CC=C1C(F)(F)F KHXIWILCHUCWGL-UHFFFAOYSA-N 0.000 description 1
• BZZWYIHKZBGTRR-UHFFFAOYSA-N ethyl 6-(4-chlorophenyl)-2-(2-cyclohexylethyl)-5-hydroxy-3-oxopyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C=2C=CC(Cl)=CC=2)=NN1CCC1CCCCC1 BZZWYIHKZBGTRR-UHFFFAOYSA-N 0.000 description 1
• NJNMMWITZVRYGI-UHFFFAOYSA-N ethyl 6-(4-chlorophenyl)-2-[(2-chlorophenyl)methyl]-5-hydroxy-3-oxopyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C=2C=CC(Cl)=CC=2)=NN1CC1=CC=CC=C1Cl NJNMMWITZVRYGI-UHFFFAOYSA-N 0.000 description 1
• WPFGTINCYLPBJW-UHFFFAOYSA-N ethyl 6-(4-chlorophenyl)-5-hydroxy-3-oxo-2-[(4-phenylphenyl)methyl]pyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C=2C=CC(Cl)=CC=2)=NN1CC(C=C1)=CC=C1C1=CC=CC=C1 WPFGTINCYLPBJW-UHFFFAOYSA-N 0.000 description 1
• AKFGLFODEFEAPV-UHFFFAOYSA-N ethyl 6-(4-fluorophenyl)-5-hydroxy-3-oxo-2-[(4-phenylphenyl)methyl]pyridazine-4-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(O)C(C=2C=CC(F)=CC=2)=NN1CC(C=C1)=CC=C1C1=CC=CC=C1 AKFGLFODEFEAPV-UHFFFAOYSA-N 0.000 description 1
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