HUE029366T2 - Bicyclic-substituted uracil derivatives and their use - Google Patents
Bicyclic-substituted uracil derivatives and their use Download PDFInfo
- Publication number
- HUE029366T2 HUE029366T2 HUE13720407A HUE13720407A HUE029366T2 HU E029366 T2 HUE029366 T2 HU E029366T2 HU E13720407 A HUE13720407 A HU E13720407A HU E13720407 A HUE13720407 A HU E13720407A HU E029366 T2 HUE029366 T2 HU E029366T2
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- HU
- Hungary
- Prior art keywords
- hydrogen
- ethyl
- mmol
- formula
- compound
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- 150000001875 compounds Chemical class 0.000 claims description 623
- 238000000034 method Methods 0.000 claims description 505
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 376
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 162
- 239000002253 acid Substances 0.000 claims description 150
- 229910052739 hydrogen Inorganic materials 0.000 claims description 141
- 239000001257 hydrogen Substances 0.000 claims description 134
- 238000006243 chemical reaction Methods 0.000 claims description 70
- 150000002431 hydrogen Chemical class 0.000 claims description 70
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 64
- 229910052731 fluorine Inorganic materials 0.000 claims description 55
- 239000011737 fluorine Substances 0.000 claims description 55
- -1 (C 1 -C 6 -alkyl Chemical group 0.000 claims description 53
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 53
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 51
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 49
- 208000035475 disorder Diseases 0.000 claims description 38
- 150000003839 salts Chemical class 0.000 claims description 38
- 239000002904 solvent Substances 0.000 claims description 35
- 239000012453 solvate Substances 0.000 claims description 34
- 239000000460 chlorine Substances 0.000 claims description 28
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 26
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 24
- 229910052801 chlorine Inorganic materials 0.000 claims description 24
- 229910052799 carbon Inorganic materials 0.000 claims description 23
- 239000003112 inhibitor Substances 0.000 claims description 23
- 125000001424 substituent group Chemical group 0.000 claims description 22
- 239000000126 substance Substances 0.000 claims description 21
- 238000011282 treatment Methods 0.000 claims description 21
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- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
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- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
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- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 8
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- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 125000003566 oxetanyl group Chemical group 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 4
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- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 3
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- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
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- 125000001153 fluoro group Chemical group F* 0.000 claims 8
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 3
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 2
- 230000009897 systematic effect Effects 0.000 claims 2
- 230000009466 transformation Effects 0.000 claims 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims 1
- 229940123413 Angiotensin II antagonist Drugs 0.000 claims 1
- 101100378101 Caenorhabditis briggsae ace-4 gene Proteins 0.000 claims 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims 1
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- 208000019693 Lung disease Diseases 0.000 claims 1
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- 101100256746 Mus musculus Setdb1 gene Proteins 0.000 claims 1
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- 101150047344 Plaa gene Proteins 0.000 claims 1
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- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims 1
- 125000005189 alkyl hydroxy group Chemical group 0.000 claims 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 claims 1
- 235000021016 apples Nutrition 0.000 claims 1
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- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 1
- 235000019788 craving Nutrition 0.000 claims 1
- 125000004783 dichloromethoxy group Chemical group ClC(O*)Cl 0.000 claims 1
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 claims 1
- RIZMRRKBZQXFOY-UHFFFAOYSA-N ethion Chemical compound CCOP(=S)(OCC)SCSP(=S)(OCC)OCC RIZMRRKBZQXFOY-UHFFFAOYSA-N 0.000 claims 1
- UHCBBWUQDAVSMS-UHFFFAOYSA-N fluoroethane Chemical compound CCF UHCBBWUQDAVSMS-UHFFFAOYSA-N 0.000 claims 1
- 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 239000006166 lysate Substances 0.000 claims 1
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- 239000002184 metal Substances 0.000 claims 1
- 239000003226 mitogen Substances 0.000 claims 1
- 239000002105 nanoparticle Substances 0.000 claims 1
- 210000005036 nerve Anatomy 0.000 claims 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 claims 1
- 210000001147 pulmonary artery Anatomy 0.000 claims 1
- 229910052705 radium Inorganic materials 0.000 claims 1
- HCWPIIXVSYCSAN-UHFFFAOYSA-N radium atom Chemical compound [Ra] HCWPIIXVSYCSAN-UHFFFAOYSA-N 0.000 claims 1
- 231100000241 scar Toxicity 0.000 claims 1
- 210000002966 serum Anatomy 0.000 claims 1
- MLGCXEBRWGEOQX-UHFFFAOYSA-N tetradifon Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)C1=CC(Cl)=C(Cl)C=C1Cl MLGCXEBRWGEOQX-UHFFFAOYSA-N 0.000 claims 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims 1
- 150000003573 thiols Chemical class 0.000 claims 1
- 229910052719 titanium Inorganic materials 0.000 claims 1
- 239000003053 toxin Substances 0.000 claims 1
- 231100000765 toxin Toxicity 0.000 claims 1
- 125000006000 trichloroethyl group Chemical group 0.000 claims 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
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- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 56
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- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 36
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- 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 31
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| MY190108A (en) * | 2013-11-08 | 2022-03-29 | Bayer Pharma AG | Salts of 1-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)-2,4- dioxo-3-[(1r)-4-(trifluormethyl)-2,3-dihydro-1h-inden-1-yl)-1,2,3,4- tetrahydropyrimidin-5-carboxylic acid |
| US9695131B2 (en) * | 2013-11-08 | 2017-07-04 | Bayer Pharma Aktiengesellschaft | Substituted uracils as chymase inhibitors |
| WO2015067630A1 (de) * | 2013-11-08 | 2015-05-14 | Bayer Pharma Aktiengesellschaft | Substituierte uracile und ihre verwendung |
| HK1223610A1 (zh) * | 2013-11-08 | 2017-08-04 | Bayer Pharma Aktiengesellschaft | 取代的1,2,4-三嗪-3,5-二酮及其作为类糜蛋白酶抑制剂的用途 |
| 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 |
| US20200230136A1 (en) | 2017-04-27 | 2020-07-23 | Bayer Aktiengesellschaft | Selective adrenoreceptor alpha2c receptor antagonists alone, or in combination with chymase inhibitors for use in the treatment and/or prophylaxis of peripheral artery diseases (pad) |
| MA52616A (fr) | 2018-05-15 | 2021-03-24 | Bayer Ag | Benzamides à substitution 1,3-thiazol-2-yl pour le traitement de maladies associées à la sensibilisation de fibres nerveuses |
| 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 |
| CN113811530B (zh) * | 2019-07-03 | 2022-07-19 | 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 |
| 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 |
| WO2022135502A1 (zh) * | 2020-12-25 | 2022-06-30 | 广东东阳光药业有限公司 | 多取代的尿嘧啶衍生物及其用途 |
| US11319319B1 (en) | 2021-04-07 | 2022-05-03 | Ventus Therapeutics U.S., Inc. | Compounds for inhibiting NLRP3 and uses thereof |
| WO2023107487A1 (en) * | 2021-12-06 | 2023-06-15 | Pretzel Therapeutics, Inc. | Lonp1 inhibitor compounds, uses and methods |
| CA3255475A1 (en) | 2022-04-05 | 2023-10-12 | Socpra Sciences Santé Et Humaines S.E.C. | CHYMASE INHIBITORS INTENDED FOR USE IN THE SELECTIVE RESOLUTION OF THROMBUS IN THROMBOTIC OR THROMBOEMBOLIC DISORDERS |
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Family Cites Families (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6403599B1 (en) * | 1995-11-08 | 2002-06-11 | Pfizer Inc | Corticotropin releasing factor antagonists |
| US6114532A (en) | 1998-02-03 | 2000-09-05 | Boehringer Ingelheim Pharma Kg | Bicyclic heterocycles, the preparation thereof, and their use as pharmaceuticals |
| DE19834044A1 (de) | 1998-07-29 | 2000-02-03 | Bayer Ag | Neue substituierte Pyrazolderivate |
| DE19834047A1 (de) | 1998-07-29 | 2000-02-03 | Bayer Ag | Substituierte Pyrazolderivate |
| US6458952B1 (en) | 1999-05-19 | 2002-10-01 | Pharmacia Corporation | Substituted polycyclic aryl and heteroaryl uracils useful for selective inhibition of the coagulation cascade |
| EP1219611A4 (en) | 1999-09-03 | 2003-03-19 | Ajinomoto Kk | NEW PROCESSES FOR THE PRODUCTION OF OXAZEPINE DERIVATIVES |
| DE19943639A1 (de) | 1999-09-13 | 2001-03-15 | Bayer Ag | Dicarbonsäurederivate mit neuartigen pharmazeutischen Eigenschaften |
| DE19943635A1 (de) | 1999-09-13 | 2001-03-15 | Bayer Ag | Neuartige Aminodicarbonsäurederivate mit pharmazeutischen Eigenschaften |
| DE19943634A1 (de) | 1999-09-13 | 2001-04-12 | Bayer Ag | Neuartige Dicarbonsäurederivate mit pharmazeutischen Eigenschaften |
| DE19943636A1 (de) | 1999-09-13 | 2001-03-15 | Bayer Ag | Neuartige Dicarbonsäurederivate mit pharmazeutischen Eigenschaften |
| GB0021315D0 (en) * | 2000-08-30 | 2000-10-18 | Dainippon Pharmaceutical Co | Heterocyclic compounds and intermediates thereof |
| AR031176A1 (es) | 2000-11-22 | 2003-09-10 | Bayer Ag | Nuevos derivados de pirazolpiridina sustituidos con piridina |
| DE10110750A1 (de) | 2001-03-07 | 2002-09-12 | Bayer Ag | Neuartige Aminodicarbonsäurederivate mit pharmazeutischen Eigenschaften |
| DE10110749A1 (de) | 2001-03-07 | 2002-09-12 | Bayer Ag | Substituierte Aminodicarbonsäurederivate |
| JP2003017508A (ja) | 2001-07-05 | 2003-01-17 | Nec Corp | 電界効果トランジスタ |
| AR038536A1 (es) | 2002-02-25 | 2005-01-19 | Upjohn Co | N-aril-2-oxazolidinona-5- carboxamidas y sus derivados |
| DE10220570A1 (de) | 2002-05-08 | 2003-11-20 | Bayer Ag | Carbamat-substituierte Pyrazolopyridine |
| JP2003342265A (ja) * | 2002-05-22 | 2003-12-03 | Senju Pharmaceut Co Ltd | トリアゾリジン誘導体およびその医薬用途 |
| EP1569905A2 (en) | 2002-12-06 | 2005-09-07 | Eli Lilly And Company | Inhibitors of monoamine uptake |
| JP4387360B2 (ja) * | 2003-08-22 | 2009-12-16 | 帝人ファーマ株式会社 | キマーゼ阻害剤を有効成分として含有する薬剤 |
| DE102004004928A1 (de) | 2004-01-31 | 2005-08-18 | Bayer Healthcare Ag | Dibenzoxazepine II |
| MXPA06010900A (es) | 2004-03-26 | 2007-02-21 | Methylgene Inc | Inhibidores de histona desacetilasa. |
| US7507748B2 (en) | 2004-07-22 | 2009-03-24 | Amgen Inc. | Substituted aryl-amine derivatives and methods of use |
| AU2005321946B2 (en) | 2004-12-23 | 2012-08-16 | Deciphera Pharmaceuticals, Llc | Enzyme modulators and treatments |
| MX2007013595A (es) | 2005-05-04 | 2008-01-24 | Renovis Inc | Compuestos heterociclicos fusionados y composiciones y usos de estos. |
| WO2007007161A2 (en) * | 2005-07-08 | 2007-01-18 | Orchid Research Laboratories Limited | Novel bio-active derivatives |
| WO2007120339A1 (en) | 2005-12-19 | 2007-10-25 | Genentech, Inc. | Pyrimidine kinase inhibitors |
| EP1987025B1 (en) | 2006-02-14 | 2009-09-16 | Pfizer Products Inc. | Benzoxazinone and benzoxazepinone oxazolidinones as antibacterial agents |
| TWI394747B (zh) * | 2006-06-23 | 2013-05-01 | Smithkline Beecham Corp | 脯胺醯基羥化酶抑制劑 |
| US7790756B2 (en) | 2006-10-11 | 2010-09-07 | Deciphera Pharmaceuticals, Llc | Kinase inhibitors useful for the treatment of myleoproliferative diseases and other proliferative diseases |
| GB0622472D0 (en) | 2006-11-10 | 2006-12-20 | Addex Pharmaceuticals Sa | Novel heterocyclic derivatives |
| AU2008219166B2 (en) | 2007-02-16 | 2013-05-16 | Amgen Inc. | Nitrogen-containing heterocyclyl ketones and their use as c-Met inhibitors |
| AU2008240313A1 (en) | 2007-04-13 | 2008-10-23 | Aj Park | Aminopyrimidines useful as kinase inhibitors |
| WO2009049112A1 (en) | 2007-10-10 | 2009-04-16 | Smithkline Beecham Corporation | Prolyl hydroxylase inhibitors |
| EP2205609B1 (de) | 2007-10-19 | 2017-03-29 | Boehringer Ingelheim International GmbH | Heterocyclus-substituierte piperazino-dihydrothienopyrimidine |
| NZ589019A (en) * | 2008-05-05 | 2012-10-26 | Merck Frosst Canada Ltd | 3, 4 - substituted piperidine derivatives as renin inhibitors |
| DE102008030091B4 (de) | 2008-06-25 | 2011-03-03 | Resprotect Gmbh | Uracilderivate und deren Verwendung |
| WO2009157418A1 (ja) | 2008-06-25 | 2009-12-30 | 第一三共株式会社 | カルボン酸化合物 |
| UA112897C2 (uk) * | 2012-05-09 | 2016-11-10 | Байєр Фарма Акцієнгезелльшафт | Біциклічно заміщені урацили та їх застосування для лікування і/або профілактики захворювань |
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