HUE035462T2 - Bicyclic substituted uracil derivatives and their use - Google Patents
Bicyclic substituted uracil derivatives and their use Download PDFInfo
- Publication number
- HUE035462T2 HUE035462T2 HUE16154186A HUE16154186A HUE035462T2 HU E035462 T2 HUE035462 T2 HU E035462T2 HU E16154186 A HUE16154186 A HU E16154186A HU E16154186 A HUE16154186 A HU E16154186A HU E035462 T2 HUE035462 T2 HU E035462T2
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- HU
- Hungary
- Prior art keywords
- hydrogen
- mmol
- ethyl
- compound
- theory
- Prior art date
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- 125000002619 bicyclic group Chemical group 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 556
- 238000000034 method Methods 0.000 claims description 392
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 350
- 229910052739 hydrogen Inorganic materials 0.000 claims description 149
- 239000001257 hydrogen Substances 0.000 claims description 148
- 239000002253 acid Substances 0.000 claims description 83
- 150000002431 hydrogen Chemical class 0.000 claims description 75
- -1 quintet Chemical group 0.000 claims description 65
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 64
- 229910052731 fluorine Inorganic materials 0.000 claims description 61
- 239000011737 fluorine Substances 0.000 claims description 61
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 59
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 57
- 208000035475 disorder Diseases 0.000 claims description 57
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 54
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 53
- 150000003839 salts Chemical class 0.000 claims description 44
- 238000011282 treatment Methods 0.000 claims description 44
- 239000000460 chlorine Substances 0.000 claims description 36
- 239000012453 solvate Substances 0.000 claims description 36
- 229910052801 chlorine Inorganic materials 0.000 claims description 32
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 31
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 30
- 238000011321 prophylaxis Methods 0.000 claims description 30
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 27
- 125000001424 substituent group Chemical group 0.000 claims description 27
- 229910052799 carbon Inorganic materials 0.000 claims description 24
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 150000002367 halogens Chemical class 0.000 claims description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 14
- 150000001721 carbon Chemical group 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- 230000002093 peripheral effect Effects 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 125000004429 atom Chemical group 0.000 claims description 11
- 125000003566 oxetanyl group Chemical group 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 9
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- 125000001153 fluoro group Chemical group F* 0.000 claims description 8
- 239000001301 oxygen Substances 0.000 claims description 8
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 6
- 229910052805 deuterium Inorganic materials 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 230000004087 circulation Effects 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 125000002393 azetidinyl group Chemical group 0.000 claims description 3
- 238000005859 coupling reaction Methods 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 208000011580 syndromic disease Diseases 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 claims description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 230000008878 coupling Effects 0.000 claims description 2
- 238000010168 coupling process Methods 0.000 claims description 2
- 125000001072 heteroaryl group Chemical group 0.000 claims description 2
- 230000037361 pathway Effects 0.000 claims description 2
- 229940035893 uracil Drugs 0.000 claims description 2
- 101150108015 STR6 gene Proteins 0.000 claims 3
- 230000009897 systematic effect Effects 0.000 claims 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 2
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- 125000006164 6-membered heteroaryl group Chemical group 0.000 claims 1
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims 1
- 206010057259 Laryngeal dysplasia Diseases 0.000 claims 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims 1
- 241000219094 Vitaceae Species 0.000 claims 1
- 238000004378 air conditioning Methods 0.000 claims 1
- 210000000481 breast Anatomy 0.000 claims 1
- 210000001627 cerebral artery Anatomy 0.000 claims 1
- 239000006184 cosolvent Substances 0.000 claims 1
- 235000014113 dietary fatty acids Nutrition 0.000 claims 1
- 238000006073 displacement reaction Methods 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 125000005680 ethenylethyl group Chemical group [H]C([H])=C([H])C([H])([H])C([H])([H])* 0.000 claims 1
- RIZMRRKBZQXFOY-UHFFFAOYSA-N ethion Chemical compound CCOP(=S)(OCC)SCSP(=S)(OCC)OCC RIZMRRKBZQXFOY-UHFFFAOYSA-N 0.000 claims 1
- 229930195729 fatty acid Natural products 0.000 claims 1
- 239000000194 fatty acid Substances 0.000 claims 1
- UHCBBWUQDAVSMS-UHFFFAOYSA-N fluoroethane Chemical compound CCF UHCBBWUQDAVSMS-UHFFFAOYSA-N 0.000 claims 1
- 125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 claims 1
- 235000021021 grapes Nutrition 0.000 claims 1
- YPNYLVXWUIEEKT-UHFFFAOYSA-N hydroxymethoxyperoxymethanol Chemical compound OCOOOCO YPNYLVXWUIEEKT-UHFFFAOYSA-N 0.000 claims 1
- 238000002372 labelling Methods 0.000 claims 1
- 230000000873 masking effect Effects 0.000 claims 1
- 125000004043 oxo group Chemical group O=* 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 238000004513 sizing Methods 0.000 claims 1
- 239000004575 stone Substances 0.000 claims 1
- 239000011593 sulfur Substances 0.000 claims 1
- 125000004001 thioalkyl group Chemical group 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 231
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 183
- 239000000203 mixture Substances 0.000 description 169
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 167
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 153
- 238000002360 preparation method Methods 0.000 description 147
- 239000011541 reaction mixture Substances 0.000 description 142
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 139
- 238000000746 purification Methods 0.000 description 139
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 114
- 239000000243 solution Substances 0.000 description 94
- 239000007787 solid Substances 0.000 description 84
- 235000011167 hydrochloric acid Nutrition 0.000 description 70
- 229960000443 hydrochloric acid Drugs 0.000 description 70
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 65
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 64
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 58
- 238000010626 work up procedure Methods 0.000 description 58
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 55
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 51
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 51
- 239000012074 organic phase Substances 0.000 description 51
- 238000010992 reflux Methods 0.000 description 51
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 44
- 238000006243 chemical reaction Methods 0.000 description 44
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 39
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 36
- 239000003480 eluent Substances 0.000 description 33
- 239000000706 filtrate Substances 0.000 description 33
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 33
- 238000001816 cooling Methods 0.000 description 32
- 230000035484 reaction time Effects 0.000 description 32
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 30
- 239000002904 solvent Substances 0.000 description 30
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 29
- 238000004128 high performance liquid chromatography Methods 0.000 description 29
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 28
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 27
- 239000003112 inhibitor Substances 0.000 description 27
- 235000019341 magnesium sulphate Nutrition 0.000 description 27
- 238000003756 stirring Methods 0.000 description 27
- 229910052700 potassium Inorganic materials 0.000 description 25
- 239000011591 potassium Substances 0.000 description 25
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 24
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 24
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 23
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 23
- 229910052786 argon Inorganic materials 0.000 description 22
- 239000011734 sodium Substances 0.000 description 22
- 229960000583 acetic acid Drugs 0.000 description 20
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- 235000011181 potassium carbonates Nutrition 0.000 description 19
- 238000002953 preparative HPLC Methods 0.000 description 19
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
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- 208000017169 kidney disease Diseases 0.000 description 17
- 238000007792 addition Methods 0.000 description 16
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 15
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- 229910052763 palladium Inorganic materials 0.000 description 15
- 230000015572 biosynthetic process Effects 0.000 description 14
- 150000003385 sodium Chemical class 0.000 description 14
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- 150000003254 radicals Chemical group 0.000 description 13
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 13
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- 239000012043 crude product Substances 0.000 description 12
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- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 11
- GHMVTBRBCJHSKM-UHFFFAOYSA-N [N].O=C1C=CNC(=O)N1 Chemical group [N].O=C1C=CNC(=O)N1 GHMVTBRBCJHSKM-UHFFFAOYSA-N 0.000 description 11
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- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 10
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- 230000003836 peripheral circulation Effects 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 9
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- 239000004480 active ingredient Substances 0.000 description 6
- 150000007942 carboxylates Chemical class 0.000 description 6
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- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 6
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- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 238000010898 silica gel chromatography Methods 0.000 description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 description 6
- 239000012312 sodium hydride Substances 0.000 description 6
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 6
- 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 6
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 6
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 5
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 5
- 208000009525 Myocarditis Diseases 0.000 description 5
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 5
- 208000001647 Renal Insufficiency Diseases 0.000 description 5
- 229910052783 alkali metal Inorganic materials 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 5
- 230000000155 isotopic effect Effects 0.000 description 5
- 201000006370 kidney failure Diseases 0.000 description 5
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- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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| UA112897C2 (uk) * | 2012-05-09 | 2016-11-10 | Байєр Фарма Акцієнгезелльшафт | Біциклічно заміщені урацили та їх застосування для лікування і/або профілактики захворювань |
| WO2015067651A1 (de) * | 2013-11-08 | 2015-05-14 | Bayer Pharma Aktiengesellschaft | Substituierte uracile als chymase inhibitoren |
| LT3066097T (lt) * | 2013-11-08 | 2018-02-12 | Bayer Pharma Aktiengesellschaft | 1-(3-metil-2-okso-2,3-dihidro-1,3-benzoksazol-6-il)-2,4-diokso-3-[(1r)-4-(trifluormetil)-2,3-dihidro-1h-inden-1-il]-1,2,3,4-tetrahidropirimidin-5-karboksirūgšties druskos |
| CN105980381A (zh) | 2013-11-08 | 2016-09-28 | 拜耳医药股份有限公司 | 取代的尿嘧啶及其用途 |
| US20160287599A1 (en) * | 2013-11-08 | 2016-10-06 | Bayer Pharma Aktiengesellschaft | Substituted 1,2,4-triazine-3,5-diones and the use thereof as chymase inhibitors |
| WO2017162661A1 (en) | 2016-03-22 | 2017-09-28 | Bayer Pharma Aktiengesellschaft | 1h-benzo[de]isoquinoline-1,3(2h)-diones |
| EP3338780A1 (de) | 2016-12-20 | 2018-06-27 | Bayer Pharma Aktiengesellschaft | Verwendung von chymaseinhibitoren zur behandlung von endometriose, post-operativer fibrose und erkrankungen die durch fibrosebildung gekennzeichnet sind |
| CA3061444A1 (en) | 2017-04-27 | 2018-11-01 | Bayer Aktiengesellschaft | Selective adrenoreceptor .alpha.2c receptor antagonists alone, or in combination with chymase inhibitors for use in the treatment and/or prophylaxis of peripheral artery diseases (pad) |
| CN112384213A (zh) | 2018-05-15 | 2021-02-19 | 拜耳公司 | 用于治疗与神经纤维敏化有关的疾病的1,3-噻唑-2-基取代的苯甲酰胺 |
| CN110229067A (zh) * | 2019-06-05 | 2019-09-13 | 南京焕然生物科技有限公司 | 一种2-氨基茚制备方法 |
| WO2021000933A1 (zh) * | 2019-07-03 | 2021-01-07 | 南京明德新药研发有限公司 | 作为糜酶抑制剂的嘧啶酮类化合物及其应用 |
| US11618751B1 (en) | 2022-03-25 | 2023-04-04 | Ventus Therapeutics U.S., Inc. | Pyrido-[3,4-d]pyridazine amine derivatives useful as NLRP3 derivatives |
| CN111440141A (zh) * | 2020-05-20 | 2020-07-24 | 安徽泽升科技有限公司 | 一种羟甲基取代芳杂环类化合物的制备方法 |
| CN114685472B (zh) * | 2020-12-25 | 2024-04-26 | 广东东阳光药业股份有限公司 | 多取代的尿嘧啶衍生物及其用途 |
| CN114671856B (zh) * | 2020-12-25 | 2023-10-20 | 广东东阳光药业股份有限公司 | 多取代的尿嘧啶衍生物及其用途 |
| WO2022135534A1 (zh) * | 2020-12-25 | 2022-06-30 | 广东东阳光药业有限公司 | 取代的含氮双环化合物及其用途 |
| US11319319B1 (en) | 2021-04-07 | 2022-05-03 | Ventus Therapeutics U.S., Inc. | Compounds for inhibiting NLRP3 and uses thereof |
| US20250051367A1 (en) * | 2021-12-06 | 2025-02-13 | Pretzel Therapeutics, Inc. | Heterocycle-containing lonp1 inhibitor compounds, uses and methods |
| EP4504201A1 (en) | 2022-04-05 | 2025-02-12 | Socpra Sciences Santé Et Humaines S.E.C. | Inhibitors of chymase for use in the selective resolution of thrombi in thrombotic or thromboembolic disorders |
| US12331048B2 (en) | 2022-10-31 | 2025-06-17 | Ventus Therapeutics U.S., Inc. | Pyrido-[3,4-d]pyridazine amine derivatives useful as NLRP3 inhibitors |
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