CN105439946B - 羧酸化合物及其制备方法和用途 - Google Patents
羧酸化合物及其制备方法和用途 Download PDFInfo
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- CN105439946B CN105439946B CN201410398333.4A CN201410398333A CN105439946B CN 105439946 B CN105439946 B CN 105439946B CN 201410398333 A CN201410398333 A CN 201410398333A CN 105439946 B CN105439946 B CN 105439946B
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- ethyl acetate
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- -1 Carboxylic acid compound Chemical class 0.000 title claims abstract description 79
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- 150000003839 salts Chemical class 0.000 claims abstract description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 15
- 238000002360 preparation method Methods 0.000 claims abstract description 14
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 claims description 35
- 229940116269 uric acid Drugs 0.000 claims description 35
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 claims description 32
- 239000003814 drug Substances 0.000 claims description 22
- 201000005569 Gout Diseases 0.000 claims description 14
- 210000004369 blood Anatomy 0.000 claims description 14
- 239000008280 blood Substances 0.000 claims description 14
- 201000010099 disease Diseases 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 241001465754 Metazoa Species 0.000 claims description 8
- OFCNXPDARWKPPY-UHFFFAOYSA-N allopurinol Chemical group OC1=NC=NC2=C1C=NN2 OFCNXPDARWKPPY-UHFFFAOYSA-N 0.000 claims description 6
- 229960003459 allopurinol Drugs 0.000 claims description 6
- BQSJTQLCZDPROO-UHFFFAOYSA-N febuxostat Chemical compound C1=C(C#N)C(OCC(C)C)=CC=C1C1=NC(C)=C(C(O)=O)S1 BQSJTQLCZDPROO-UHFFFAOYSA-N 0.000 claims description 6
- 229960005101 febuxostat Drugs 0.000 claims description 6
- 108010093894 Xanthine oxidase Proteins 0.000 claims description 5
- 210000000056 organ Anatomy 0.000 claims description 5
- 201000001431 Hyperuricemia Diseases 0.000 claims description 4
- 102000005773 Xanthine dehydrogenase Human genes 0.000 claims description 4
- 108010091383 Xanthine dehydrogenase Proteins 0.000 claims description 4
- 230000002159 abnormal effect Effects 0.000 claims description 4
- 206010003246 arthritis Diseases 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 208000011580 syndromic disease Diseases 0.000 claims description 4
- 206010007027 Calculus urinary Diseases 0.000 claims description 3
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
- 206010020772 Hypertension Diseases 0.000 claims description 3
- 208000000913 Kidney Calculi Diseases 0.000 claims description 3
- 206010029148 Nephrolithiasis Diseases 0.000 claims description 3
- 150000003863 ammonium salts Chemical class 0.000 claims description 3
- 230000029142 excretion Effects 0.000 claims description 3
- 208000017169 kidney disease Diseases 0.000 claims description 3
- 229940124186 Dehydrogenase inhibitor Drugs 0.000 claims description 2
- 206010018634 Gouty Arthritis Diseases 0.000 claims description 2
- 201000002980 Hyperparathyroidism Diseases 0.000 claims description 2
- 229940122272 Oxidoreductase inhibitor Drugs 0.000 claims description 2
- 201000004681 Psoriasis Diseases 0.000 claims description 2
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 2
- 229940123769 Xanthine oxidase inhibitor Drugs 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 2
- 208000029078 coronary artery disease Diseases 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 208000018937 joint inflammation Diseases 0.000 claims description 2
- 201000006370 kidney failure Diseases 0.000 claims description 2
- 208000008127 lead poisoning Diseases 0.000 claims description 2
- 239000002457 oxidoreductase inhibitor Substances 0.000 claims description 2
- 230000000306 recurrent effect Effects 0.000 claims description 2
- 201000000306 sarcoidosis Diseases 0.000 claims description 2
- 208000008281 urolithiasis Diseases 0.000 claims description 2
- 239000003064 xanthine oxidase inhibitor Substances 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims 1
- 230000001737 promoting effect Effects 0.000 claims 1
- 239000000651 prodrug Substances 0.000 abstract description 14
- 229940002612 prodrug Drugs 0.000 abstract description 14
- 239000012453 solvate Substances 0.000 abstract description 13
- 239000000463 material Substances 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 309
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 105
- 230000015572 biosynthetic process Effects 0.000 description 105
- 238000003786 synthesis reaction Methods 0.000 description 105
- 238000006243 chemical reaction Methods 0.000 description 95
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 90
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 88
- 150000001875 compounds Chemical class 0.000 description 82
- 239000012074 organic phase Substances 0.000 description 82
- 239000011541 reaction mixture Substances 0.000 description 75
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 70
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 69
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 60
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 58
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 50
- 239000012267 brine Substances 0.000 description 50
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- 229910052757 nitrogen Inorganic materials 0.000 description 45
- 239000000243 solution Substances 0.000 description 45
- 238000005160 1H NMR spectroscopy Methods 0.000 description 44
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 41
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 40
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 38
- 239000000741 silica gel Substances 0.000 description 38
- 229910002027 silica gel Inorganic materials 0.000 description 38
- 238000001035 drying Methods 0.000 description 37
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 36
- 239000003208 petroleum Substances 0.000 description 36
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 35
- 239000000203 mixture Substances 0.000 description 34
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 32
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 29
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 27
- 239000012265 solid product Substances 0.000 description 27
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 26
- 239000000047 product Substances 0.000 description 25
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 22
- 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 22
- 239000012071 phase Substances 0.000 description 22
- 239000007787 solid Substances 0.000 description 22
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 21
- 229910052739 hydrogen Inorganic materials 0.000 description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 20
- 229910000027 potassium carbonate Inorganic materials 0.000 description 20
- 229910052799 carbon Inorganic materials 0.000 description 18
- 238000001816 cooling Methods 0.000 description 17
- 239000001257 hydrogen Substances 0.000 description 17
- 229910052736 halogen Inorganic materials 0.000 description 16
- 150000002367 halogens Chemical class 0.000 description 16
- 229910000029 sodium carbonate Inorganic materials 0.000 description 16
- 239000005457 ice water Substances 0.000 description 15
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 14
- 238000001914 filtration Methods 0.000 description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 13
- 238000010438 heat treatment Methods 0.000 description 13
- 150000002431 hydrogen Chemical class 0.000 description 13
- 238000010791 quenching Methods 0.000 description 13
- 239000008346 aqueous phase Substances 0.000 description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 12
- 239000000126 substance Substances 0.000 description 12
- 125000001424 substituent group Chemical group 0.000 description 12
- 229940079593 drug Drugs 0.000 description 11
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 11
- 101000821903 Homo sapiens Solute carrier family 22 member 12 Proteins 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 10
- 125000002993 cycloalkylene group Chemical group 0.000 description 10
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 10
- 229910052938 sodium sulfate Inorganic materials 0.000 description 10
- 229910052979 sodium sulfide Inorganic materials 0.000 description 10
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 10
- 235000011152 sodium sulphate Nutrition 0.000 description 10
- 229910052717 sulfur Inorganic materials 0.000 description 10
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 9
- 102100021495 Solute carrier family 22 member 12 Human genes 0.000 description 9
- 238000000605 extraction Methods 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- JRHLVNAWLWIHDN-UHFFFAOYSA-N methyl 2-[1-(sulfanylmethyl)cyclopropyl]acetate Chemical compound COC(=O)CC1(CS)CC1 JRHLVNAWLWIHDN-UHFFFAOYSA-N 0.000 description 9
- 239000000376 reactant Substances 0.000 description 9
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 8
- 241000282414 Homo sapiens Species 0.000 description 8
- 125000004093 cyano group Chemical group *C#N 0.000 description 8
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 8
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
- 230000000171 quenching effect Effects 0.000 description 8
- 238000005406 washing Methods 0.000 description 8
- QADXKWUCCGPQNR-UHFFFAOYSA-N 3-bromo-4-chloropyridine Chemical compound ClC1=CC=NC=C1Br QADXKWUCCGPQNR-UHFFFAOYSA-N 0.000 description 7
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 7
- 239000003054 catalyst Substances 0.000 description 7
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- 230000000694 effects Effects 0.000 description 7
- 239000011737 fluorine Substances 0.000 description 7
- 229910052731 fluorine Inorganic materials 0.000 description 7
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- 238000004237 preparative chromatography Methods 0.000 description 7
- RHASGUGQMCVYMQ-UHFFFAOYSA-N C(#N)C1=CC=C(C=C1)C=1C=NC=CC=1SCC1(CC1)CC(=O)O Chemical compound C(#N)C1=CC=C(C=C1)C=1C=NC=CC=1SCC1(CC1)CC(=O)O RHASGUGQMCVYMQ-UHFFFAOYSA-N 0.000 description 6
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- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 125000002947 alkylene group Chemical group 0.000 description 6
- 150000001450 anions Chemical class 0.000 description 6
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 6
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- 229910052708 sodium Inorganic materials 0.000 description 6
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- CEBAHYWORUOILU-UHFFFAOYSA-N (4-cyanophenyl)boronic acid Chemical compound OB(O)C1=CC=C(C#N)C=C1 CEBAHYWORUOILU-UHFFFAOYSA-N 0.000 description 5
- 239000004471 Glycine Substances 0.000 description 5
- 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 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- GPFGVZAQKJPYAT-UHFFFAOYSA-N methyl 1-(bromomethyl)cyclopropane-1-carboxylate Chemical compound COC(=O)C1(CBr)CC1 GPFGVZAQKJPYAT-UHFFFAOYSA-N 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 235000011056 potassium acetate Nutrition 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
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- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 4
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 4
- 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 4
- YFVKJADLORAGCL-UHFFFAOYSA-N 4-(4-chloropyridin-3-yl)benzonitrile Chemical compound ClC1=C(C=NC=C1)C1=CC=C(C#N)C=C1 YFVKJADLORAGCL-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- MJDVQWFWTWDIQH-UHFFFAOYSA-N C(#N)C1=CC=C(C2=CC=CC=C12)C=1C=NC=CC=1SCC1(CC1)CC(=O)O Chemical compound C(#N)C1=CC=C(C2=CC=CC=C12)C=1C=NC=CC=1SCC1(CC1)CC(=O)O MJDVQWFWTWDIQH-UHFFFAOYSA-N 0.000 description 4
- GVRDJXZMUPXEQK-UHFFFAOYSA-N C(#N)C1=CN(C2=CC=CC=C12)C=1C=NC=CC=1SC(C(=O)O)(C)C Chemical compound C(#N)C1=CN(C2=CC=CC=C12)C=1C=NC=CC=1SC(C(=O)O)(C)C GVRDJXZMUPXEQK-UHFFFAOYSA-N 0.000 description 4
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- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 150000001555 benzenes Chemical group 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
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- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
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- 125000005842 heteroatom Chemical group 0.000 description 4
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 4
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- PQUSVJVVRXWKDG-UHFFFAOYSA-N methyl 2-bromo-2-methylpropanoate Chemical compound COC(=O)C(C)(C)Br PQUSVJVVRXWKDG-UHFFFAOYSA-N 0.000 description 4
- 125000003566 oxetanyl group Chemical group 0.000 description 4
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 4
- 230000032258 transport Effects 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
- 210000005239 tubule Anatomy 0.000 description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 3
- BEXKBLOOYLIFRF-UHFFFAOYSA-N 1-(4-chloropyridin-3-yl)indole-3-carbonitrile Chemical compound ClC1=C(C=NC=C1)N1C=C(C2=CC=CC=C12)C#N BEXKBLOOYLIFRF-UHFFFAOYSA-N 0.000 description 3
- QAPGFAJKJBYGAT-UHFFFAOYSA-N 1-(4-chloropyridin-3-yl)isoquinoline-4-carbonitrile Chemical compound ClC1=C(C=NC=C1)C1=NC=C(C2=CC=CC=C12)C#N QAPGFAJKJBYGAT-UHFFFAOYSA-N 0.000 description 3
- CHIFTAQVXHNVRW-UHFFFAOYSA-N 1h-indole-3-carbonitrile Chemical compound C1=CC=C2C(C#N)=CNC2=C1 CHIFTAQVXHNVRW-UHFFFAOYSA-N 0.000 description 3
- OJMSFYDWZDKGJI-UHFFFAOYSA-N 2,2-dimethylthietane Chemical compound CC1(C)CCS1 OJMSFYDWZDKGJI-UHFFFAOYSA-N 0.000 description 3
- YYBOLPLTQDKXPM-UHFFFAOYSA-N 2-[3-(4-cyanonaphthalen-1-yl)pyridin-4-yl]sulfanyl-2-methylpropanoic acid Chemical class OC(=O)C(C)(C)SC1=CC=NC=C1C1=CC=C(C#N)C2=CC=CC=C12 YYBOLPLTQDKXPM-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 3
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
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- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
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| PCT/CN2015/086605 WO2016023460A1 (zh) | 2014-08-13 | 2015-08-11 | 羧酸化合物及其制备方法和用途 |
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| WO2017114352A1 (en) * | 2015-12-28 | 2017-07-06 | Chongqing Fochon Pharmaceutical Co., Ltd. | Indolizine derivatives, composition and methods of use |
| CN105884807A (zh) * | 2016-04-26 | 2016-08-24 | 昆药集团股份有限公司 | 硼酸频那醇酯衍生物的制备方法、硫代乙酸盐化合物的制备方法 |
| CN106748987B (zh) * | 2016-11-18 | 2019-05-31 | 昆药集团股份有限公司 | 2-((3-(4-氰基萘-1-基)吡啶-4-基)硫基)-2-甲基丙酸钠盐的晶型 |
| US10752596B2 (en) * | 2017-10-04 | 2020-08-25 | Japan Tobacco Inc. | Nitrogen-containing heteroaryl compound and pharmaceutical use thereof |
| CN108084153A (zh) * | 2017-12-20 | 2018-05-29 | 广东赛烽医药科技有限公司 | 吡啶基硫代乙酸化合物、组合物及其应用 |
| CN108069940B (zh) * | 2017-12-20 | 2021-04-30 | 广东赛烽医药科技有限公司 | 硫代乙酸化合物、组合物及其应用 |
| CN108440397B (zh) * | 2018-03-06 | 2020-06-05 | 南方医科大学 | 3-(萘-1-甲基取代)吡啶衍生物及其合成方法和应用 |
| WO2019183835A1 (en) * | 2018-03-28 | 2019-10-03 | Inventisbio Shanghai Ltd. | Novel salt forms of urat-1 inhibitors |
| CN108484494B (zh) * | 2018-06-15 | 2021-07-30 | 沈阳药科大学 | 2-氧代-1,2-二氢吡啶-4-甲酸类化合物 |
| CN111943957B (zh) * | 2019-05-17 | 2023-01-06 | 中国医学科学院药物研究所 | 喹啉甲酰胺类化合物及其制备方法和用途 |
| CN113493407B (zh) * | 2020-04-03 | 2025-01-28 | 中国医学科学院药物研究所 | 一种吡啶类化合物及其制法和药物用途 |
| AR124985A1 (es) * | 2021-03-01 | 2023-05-24 | Orion Corp | Nuevas formas de sal de un inhibidor de cyp11a1 estructurado en 4h-piran-4-ona |
| EP4301749A1 (en) * | 2021-03-01 | 2024-01-10 | Orion Corporation | Solid forms of a 4h-pyran-4-one structured cyp11a1 inhibitor |
| CN113979931B (zh) * | 2021-10-08 | 2023-06-13 | 南方医科大学 | 一种吡啶3-胺衍生物及其制备方法和应用 |
| US20250282753A1 (en) * | 2022-04-27 | 2025-09-11 | Atom Bioscience America Corporation | Compounds useful for reducing uric acid |
| WO2025060752A1 (zh) * | 2023-09-19 | 2025-03-27 | 湘北威尔曼制药股份有限公司 | 一种硫醚衍生物及其制备方法和应用 |
| WO2025060786A1 (zh) * | 2023-09-19 | 2025-03-27 | 湘北威尔曼制药股份有限公司 | 一种六元并五元稠环衍生物及其制备方法和应用 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1791572A (zh) * | 2003-04-07 | 2006-06-21 | 阿斯利康(瑞典)有限公司 | 新化合物 |
| CN103068801A (zh) * | 2010-06-16 | 2013-04-24 | 亚德生化公司 | 硫代乙酸盐化合物、组合物及其使用方法 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19541146A1 (de) * | 1995-10-25 | 1997-04-30 | Schering Ag | Imidazolderivate und deren Verwendung als Stickstoffmonoxid-Synthase-Inhibitoren |
| FR2903984B1 (fr) * | 2006-07-24 | 2008-10-03 | Genfit Sa | Derives d'imidazolones substitues, preparation et utilisations |
| ES2470329T3 (es) * | 2009-08-28 | 2014-06-23 | Daiichi Sankyo Company, Limited | Derivado del ácido 3-(biariloxi) priopi�nico |
| EP2582664A4 (en) * | 2010-06-16 | 2014-07-09 | Ardea Biosciences Inc | PHENYL THIOACETATE COMPOUNDS AND COMPOSITIONS AND METHOD FOR THEIR USE |
| UA114304C2 (uk) * | 2011-11-03 | 2017-05-25 | Ардеа Біосайєнсіс, Інк. | Спосіб зниження сироваткових рівнів сечової кислоти у людини |
| JP6067031B2 (ja) * | 2012-01-04 | 2017-01-25 | ファイザー・リミテッドPfizer Limited | N−アミノスルホニルベンズアミド |
| WO2013158422A1 (en) * | 2012-04-17 | 2013-10-24 | E. I. Du Pont De Nemours And Company | Heterocyclic compounds for controlling invertebrate pests |
| CN105439946B (zh) * | 2014-08-13 | 2018-02-02 | 益方生物科技(上海)有限公司 | 羧酸化合物及其制备方法和用途 |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1791572A (zh) * | 2003-04-07 | 2006-06-21 | 阿斯利康(瑞典)有限公司 | 新化合物 |
| CN103068801A (zh) * | 2010-06-16 | 2013-04-24 | 亚德生化公司 | 硫代乙酸盐化合物、组合物及其使用方法 |
Non-Patent Citations (2)
| Title |
|---|
| 《Rhodium-Catalyzed Direct Amination of Arenes with Nitrosobenzenes: A New Route to Diarylamines》;DU,Juanjuan等;《Chem. Eur. J. 》;20140326;第20卷(第19期);第5727-5731页 * |
| 《Silicaethylphosphatrioxaadamantane—A new support for palladium catalysts and evaluation in Suzuki coupling reactions》;GUINO,Meritxell等;《Journal of Molecular Catalysis A: Chemical》;20081001;第293卷(第1-2期);第25-30页 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106573908A (zh) * | 2014-08-13 | 2017-04-19 | 上海页岩科技有限公司 | 羧酸化合物及其制备方法和用途 |
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| JP2017524704A (ja) | 2017-08-31 |
| AU2015303597A1 (en) | 2017-03-09 |
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| EP3181557B1 (en) | 2023-03-01 |
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| US9856239B1 (en) | 2018-01-02 |
| EP3181557A1 (en) | 2017-06-21 |
| NZ729037A (en) | 2023-07-28 |
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| US20180022736A1 (en) | 2018-01-25 |
| CN106573908A (zh) | 2017-04-19 |
| AU2015303597B2 (en) | 2019-09-19 |
| KR102474640B1 (ko) | 2022-12-05 |
| KR20170042687A (ko) | 2017-04-19 |
| CA2956045A1 (en) | 2016-02-18 |
| CA2956045C (en) | 2022-10-04 |
| IL250524A0 (en) | 2017-03-30 |
| CN106573908B (zh) | 2021-02-05 |
| CN105439946A (zh) | 2016-03-30 |
| EP3181557A4 (en) | 2018-05-30 |
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