BR112020004857A2 - composto heteroarila contendo hidrogênio, e uso farmacêutico do mesmo - Google Patents
composto heteroarila contendo hidrogênio, e uso farmacêutico do mesmo Download PDFInfo
- Publication number
- BR112020004857A2 BR112020004857A2 BR112020004857-7A BR112020004857A BR112020004857A2 BR 112020004857 A2 BR112020004857 A2 BR 112020004857A2 BR 112020004857 A BR112020004857 A BR 112020004857A BR 112020004857 A2 BR112020004857 A2 BR 112020004857A2
- Authority
- BR
- Brazil
- Prior art keywords
- compound
- pharmaceutically acceptable
- acceptable salt
- nmr
- alkyl
- Prior art date
Links
- 239000001257 hydrogen Substances 0.000 title claims description 45
- 229910052739 hydrogen Inorganic materials 0.000 title claims description 45
- -1 heteroaryl compound Chemical class 0.000 title description 52
- 125000004435 hydrogen atom Chemical class [H]* 0.000 title description 12
- 150000001875 compounds Chemical class 0.000 claims abstract description 276
- 150000003839 salts Chemical class 0.000 claims abstract description 245
- 108091006303 SLC2A9 Proteins 0.000 claims abstract description 47
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 30
- 102100022720 Solute carrier family 2, facilitated glucose transporter member 6 Human genes 0.000 claims abstract 5
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 46
- 238000004519 manufacturing process Methods 0.000 claims description 46
- 229910052736 halogen Inorganic materials 0.000 claims description 45
- 150000002367 halogens Chemical class 0.000 claims description 45
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 43
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 39
- 201000001431 Hyperuricemia Diseases 0.000 claims description 37
- 238000000034 method Methods 0.000 claims description 36
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 35
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 31
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 27
- 125000004432 carbon atom Chemical group C* 0.000 claims description 25
- 125000005842 heteroatom Chemical group 0.000 claims description 24
- 125000001424 substituent group Chemical group 0.000 claims description 23
- 239000003795 chemical substances by application Substances 0.000 claims description 22
- 238000011282 treatment Methods 0.000 claims description 22
- 238000011321 prophylaxis Methods 0.000 claims description 21
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 20
- 201000005569 Gout Diseases 0.000 claims description 20
- 201000010099 disease Diseases 0.000 claims description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
- 125000006413 ring segment Chemical group 0.000 claims description 18
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 17
- 125000000623 heterocyclic group Chemical group 0.000 claims description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 14
- 230000005764 inhibitory process Effects 0.000 claims description 12
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
- 239000001301 oxygen Substances 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 241000124008 Mammalia Species 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 239000003112 inhibitor Substances 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 125000004434 sulfur atom Chemical group 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 150000001924 cycloalkanes Chemical class 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 3
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 claims description 2
- KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 1
- 150000002431 hydrogen Chemical group 0.000 claims 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 182
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 182
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 117
- 239000000203 mixture Substances 0.000 description 115
- 239000000243 solution Substances 0.000 description 108
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 80
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 69
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 60
- 239000002904 solvent Substances 0.000 description 58
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 57
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 57
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- 230000002829 reductive effect Effects 0.000 description 53
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 52
- 238000001914 filtration Methods 0.000 description 52
- 238000006243 chemical reaction Methods 0.000 description 51
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 44
- 102100030935 Solute carrier family 2, facilitated glucose transporter member 9 Human genes 0.000 description 40
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 40
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 39
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 31
- 239000007787 solid Substances 0.000 description 29
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 28
- 229910052938 sodium sulfate Inorganic materials 0.000 description 28
- 235000011152 sodium sulphate Nutrition 0.000 description 28
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 27
- 229940116269 uric acid Drugs 0.000 description 27
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 26
- 238000005481 NMR spectroscopy Methods 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 239000000706 filtrate Substances 0.000 description 24
- 210000004027 cell Anatomy 0.000 description 23
- 239000002585 base Substances 0.000 description 22
- 239000003054 catalyst Substances 0.000 description 22
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 239000012046 mixed solvent Substances 0.000 description 21
- 239000012044 organic layer Substances 0.000 description 21
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 20
- 238000004587 chromatography analysis Methods 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 18
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 18
- 239000000047 product Substances 0.000 description 18
- 239000000741 silica gel Substances 0.000 description 18
- 229910002027 silica gel Inorganic materials 0.000 description 18
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 description 17
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 15
- 239000002253 acid Substances 0.000 description 15
- 239000013078 crystal Substances 0.000 description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 15
- 229910052763 palladium Inorganic materials 0.000 description 14
- 238000002360 preparation method Methods 0.000 description 14
- 229910000160 potassium phosphate Inorganic materials 0.000 description 13
- 235000011009 potassium phosphates Nutrition 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 241000282412 Homo Species 0.000 description 12
- 239000012298 atmosphere Substances 0.000 description 12
- YZJHGMZVPWIXMX-UHFFFAOYSA-N 4-[2-(4-methoxyphenyl)-5-(3-methoxypropyl)pyridin-3-yl]benzoic acid Chemical compound COC1=CC=C(C=C1)C1=NC=C(C=C1C1=CC=C(C(=O)O)C=C1)CCCOC YZJHGMZVPWIXMX-UHFFFAOYSA-N 0.000 description 11
- 101001010113 Homo sapiens Solute carrier family 2, facilitated glucose transporter member 9 Proteins 0.000 description 11
- 102000055876 human SLC2A9 Human genes 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 10
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].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 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 10
- 210000003734 kidney Anatomy 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 9
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N benzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 9
- 239000000460 chlorine Substances 0.000 description 9
- 208000020832 chronic kidney disease Diseases 0.000 description 9
- 239000011261 inert gas Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- XVFKXIZNEOKCMC-UHFFFAOYSA-N 4-[3-(3,5-difluoro-4-methoxyphenyl)-6-(3-methoxypropyl)pyrazin-2-yl]benzoic acid Chemical compound FC=1C=C(C=C(C=1OC)F)C=1C(=NC(=CN=1)CCCOC)C1=CC=C(C(=O)O)C=C1 XVFKXIZNEOKCMC-UHFFFAOYSA-N 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 108010092464 Urate Oxidase Proteins 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 239000012299 nitrogen atmosphere Substances 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 229910052751 metal Inorganic materials 0.000 description 7
- 239000002184 metal Substances 0.000 description 7
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 description 7
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 7
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 7
- 230000001575 pathological effect Effects 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- 201000004681 Psoriasis Diseases 0.000 description 6
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- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 235000015165 citric acid Nutrition 0.000 description 6
- 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 6
- FJBFPHVGVWTDIP-UHFFFAOYSA-N dibromomethane Chemical compound BrCBr FJBFPHVGVWTDIP-UHFFFAOYSA-N 0.000 description 6
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- 230000002140 halogenating effect Effects 0.000 description 6
- 150000002430 hydrocarbons Chemical group 0.000 description 6
- CSKWLYRLGYQRGV-UHFFFAOYSA-N 2-chloro-3-[(2-methylpropan-2-yl)oxy]pyrazine Chemical compound CC(C)(C)OC1=NC=CN=C1Cl CSKWLYRLGYQRGV-UHFFFAOYSA-N 0.000 description 5
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 5
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- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 5
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- VNFWTIYUKDMAOP-UHFFFAOYSA-N sphos Chemical group COC1=CC=CC(OC)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 VNFWTIYUKDMAOP-UHFFFAOYSA-N 0.000 description 5
- 229910052717 sulfur Inorganic materials 0.000 description 5
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- NCBPWYYWONONJH-UHFFFAOYSA-N 4-[2-(4-methoxyphenyl)-5-(3-methoxypropyl)pyridin-3-yl]-2-methylbenzoic acid Chemical compound COC1=CC=C(C=C1)C1=NC=C(C=C1C1=CC(=C(C(=O)O)C=C1)C)CCCOC NCBPWYYWONONJH-UHFFFAOYSA-N 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
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- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
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- SUMDYPCJJOFFON-UHFFFAOYSA-N beta-hydroxyethanesulfonic acid Natural products OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 4
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 4
- 239000004327 boric acid Substances 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
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- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
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- 150000007522 mineralic acids Chemical class 0.000 description 4
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/12—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4418—Non condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4433—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
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- A—HUMAN NECESSITIES
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
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- A—HUMAN NECESSITIES
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—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
- 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
- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
- C07D213/46—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—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
- 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
- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/55—Acids; Esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/14—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals
- C07D217/16—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/10—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing aromatic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2017-194005 | 2017-10-04 | ||
| JP2017194005 | 2017-10-04 | ||
| PCT/JP2018/037007 WO2019069973A1 (ja) | 2017-10-04 | 2018-10-03 | 含窒素ヘテロアリール化合物およびその医薬用途 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BR112020004857A2 true BR112020004857A2 (pt) | 2020-09-15 |
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| CN110156698B (zh) * | 2019-06-06 | 2020-10-13 | 沈阳海诺威医药科技有限公司 | 2-苯基-1,6-二氢嘧啶-5-甲酸衍生物的制备方法和用途 |
| CN113181206B (zh) * | 2021-04-30 | 2023-07-14 | 青岛大学 | 与高尿酸血症伴高血脂、高血糖治疗相关基因SLC2A9的siRNA及其应用 |
| EP4460496A1 (en) * | 2022-01-07 | 2024-11-13 | Horizon Therapeutics Ireland DAC | Heterocyclic inhibitors of glut9 for treatment of disease |
| CN114805192B (zh) * | 2022-03-30 | 2023-05-23 | 华南理工大学 | 一种含2-羟基苯甲酸的三环类xor/urat1双重抑制剂及其制备方法与应用 |
| WO2024167952A1 (en) * | 2023-02-08 | 2024-08-15 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Oxidatively cleavable organophosphate drugs |
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| US5861419A (en) | 1996-07-18 | 1999-01-19 | Merck Frosst Canad, Inc. | Substituted pyridines as selective cyclooxygenase-2 inhibitors |
| SI0912518T1 (en) * | 1996-07-18 | 2003-12-31 | Merck Frosst Canada & Co. | Substituted pyridines as selective cyclooxygenase-2 inhibitors |
| HUP0101137A3 (en) * | 1998-04-10 | 2003-03-28 | Japan Tobacco Inc | Anticoagulant amidines and their pharmaceutical use |
| EP1653969A4 (en) * | 2003-08-07 | 2006-12-20 | Japan Tobacco Inc | PYRROLO 1,2-B PYRIDAZINE DERIVATIVES |
| JP2008536950A (ja) * | 2005-04-18 | 2008-09-11 | ニューロジェン・コーポレーション | 置換ヘテロアリールのcb1拮抗薬 |
| JP2007176933A (ja) | 2005-11-29 | 2007-07-12 | Tanabe Seiyaku Co Ltd | 医薬組成物 |
| JP5162827B2 (ja) * | 2005-12-27 | 2013-03-13 | ぺんてる株式会社 | 鉛筆芯の製造方法 |
| JP5330990B2 (ja) * | 2007-04-11 | 2013-10-30 | キッセイ薬品工業株式会社 | 含窒素複素環化合物およびそれを含有する医薬組成物 |
| JP2009016193A (ja) * | 2007-07-05 | 2009-01-22 | Daihen Corp | 電気機器用樹脂ブッシング |
| HRP20140705T1 (hr) * | 2009-07-17 | 2014-09-12 | Japan Tobacco, Inc. | Spoj triazolopiridina i njegovo djelovanje kao inhibitora prolil hidroksilaze i induktora proizvodnje eritropoetina |
| CN110386876A (zh) | 2010-03-24 | 2019-10-29 | 俄亥俄州立大学 | 用于葡萄糖转运抑制的组合物和方法 |
| AR081930A1 (es) * | 2010-06-16 | 2012-10-31 | Ardea Biosciences Inc | Compuestos de tioacetato |
| 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 |
| CN104306363B (zh) * | 2014-10-31 | 2017-06-06 | 南京葆赫生物技术有限公司 | 芪类衍生物及其药学可接受的盐在制备治疗高尿酸血症药物中的应用 |
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- 2018-10-03 JP JP2018188038A patent/JP7125882B2/ja active Active
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- 2018-10-03 KR KR1020207012149A patent/KR20200064101A/ko not_active Withdrawn
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- 2018-10-03 BR BR112020004857-7A patent/BR112020004857A2/pt not_active Application Discontinuation
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| US20190152926A1 (en) | 2019-05-23 |
| CN111148735A (zh) | 2020-05-12 |
| AU2018345221A1 (en) | 2020-05-07 |
| US10752596B2 (en) | 2020-08-25 |
| RU2020115045A (ru) | 2021-11-08 |
| CL2020000898A1 (es) | 2020-08-14 |
| PE20200846A1 (es) | 2020-08-18 |
| MX2020003816A (es) | 2020-08-13 |
| KR20200064101A (ko) | 2020-06-05 |
| EP3693358A1 (en) | 2020-08-12 |
| CA3074989A1 (en) | 2019-04-11 |
| CO2020003977A2 (es) | 2020-04-24 |
| JP2019065009A (ja) | 2019-04-25 |
| AR113270A1 (es) | 2020-03-11 |
| CN111148735B (zh) | 2023-08-08 |
| IL273573A (en) | 2020-05-31 |
| WO2019069973A1 (ja) | 2019-04-11 |
| TW201922706A (zh) | 2019-06-16 |
| PH12020550403A1 (en) | 2021-02-15 |
| SG11202003005PA (en) | 2020-04-29 |
| EP3693358B1 (en) | 2023-02-22 |
| EP3693358A4 (en) | 2021-06-02 |
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