JP5645961B2 - ３，４，４ａ，１０ｂ−テトラヒドロ−１Ｈ−チオピラノ−［４，３−ｃ］イソキノリン誘導体 - Google Patents
３，４，４ａ，１０ｂ−テトラヒドロ−１Ｈ−チオピラノ−［４，３−ｃ］イソキノリン誘導体 Download PDFInfo
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- JP5645961B2 JP5645961B2 JP2012543701A JP2012543701A JP5645961B2 JP 5645961 B2 JP5645961 B2 JP 5645961B2 JP 2012543701 A JP2012543701 A JP 2012543701A JP 2012543701 A JP2012543701 A JP 2012543701A JP 5645961 B2 JP5645961 B2 JP 5645961B2
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- Prior art keywords
- methyl
- ethyl
- compound
- oxadiazol
- phenyl
- Prior art date
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- ZQCSTHXMOLTGJA-UHFFFAOYSA-N 3,4,4a,10b-tetrahydro-1h-thiopyrano[4,3-c]isoquinoline Chemical class N1=CC2=CC=CC=C2C2C1CCSC2 ZQCSTHXMOLTGJA-UHFFFAOYSA-N 0.000 title description 6
- -1 pyrazol-4-yl Chemical group 0.000 claims description 823
- 150000001875 compounds Chemical class 0.000 claims description 723
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 167
- 229910052717 sulfur Inorganic materials 0.000 claims description 121
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 95
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 94
- 239000008194 pharmaceutical composition Substances 0.000 claims description 51
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 49
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 48
- 238000011282 treatment Methods 0.000 claims description 47
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 45
- 201000010099 disease Diseases 0.000 claims description 42
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 37
- 239000003814 drug Substances 0.000 claims description 26
- 229910052731 fluorine Inorganic materials 0.000 claims description 26
- 239000011737 fluorine Substances 0.000 claims description 26
- 238000004519 manufacturing process Methods 0.000 claims description 26
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 25
- 230000002265 prevention Effects 0.000 claims description 25
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 23
- 229940124597 therapeutic agent Drugs 0.000 claims description 21
- 230000001684 chronic effect Effects 0.000 claims description 20
- 125000001153 fluoro group Chemical group F* 0.000 claims description 17
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 15
- 239000002571 phosphodiesterase inhibitor Substances 0.000 claims description 15
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 208000023504 respiratory system disease Diseases 0.000 claims description 12
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 11
- 230000001154 acute effect Effects 0.000 claims description 11
- FNKQXYHWGSIFBK-RPDRRWSUSA-N sapropterin Chemical compound N1=C(N)NC(=O)C2=C1NC[C@H]([C@@H](O)[C@@H](O)C)N2 FNKQXYHWGSIFBK-RPDRRWSUSA-N 0.000 claims description 11
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 11
- 208000006673 asthma Diseases 0.000 claims description 10
- 229940099471 Phosphodiesterase inhibitor Drugs 0.000 claims description 9
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 8
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 8
- 208000029523 Interstitial Lung disease Diseases 0.000 claims description 8
- 206010014561 Emphysema Diseases 0.000 claims description 7
- 239000000867 Lipoxygenase Inhibitor Substances 0.000 claims description 7
- 239000002671 adjuvant Substances 0.000 claims description 7
- 239000000048 adrenergic agonist Substances 0.000 claims description 7
- 229940126157 adrenergic receptor agonist Drugs 0.000 claims description 7
- 206010006451 bronchitis Diseases 0.000 claims description 7
- 239000000812 cholinergic antagonist Substances 0.000 claims description 7
- 239000003246 corticosteroid Substances 0.000 claims description 7
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 7
- 239000003112 inhibitor Substances 0.000 claims description 7
- 239000003199 leukotriene receptor blocking agent Substances 0.000 claims description 7
- 206010006458 Bronchitis chronic Diseases 0.000 claims description 6
- 229940127291 Calcium channel antagonist Drugs 0.000 claims description 6
- 229940118365 Endothelin receptor antagonist Drugs 0.000 claims description 6
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 6
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 6
- 239000003242 anti bacterial agent Substances 0.000 claims description 6
- 239000003146 anticoagulant agent Substances 0.000 claims description 6
- 229940127219 anticoagulant drug Drugs 0.000 claims description 6
- 239000002876 beta blocker Substances 0.000 claims description 6
- 229940097320 beta blocking agent Drugs 0.000 claims description 6
- 239000000480 calcium channel blocker Substances 0.000 claims description 6
- 208000007451 chronic bronchitis Diseases 0.000 claims description 6
- 239000002934 diuretic Substances 0.000 claims description 6
- 229940030606 diuretics Drugs 0.000 claims description 6
- 239000003119 guanylate cyclase activator Substances 0.000 claims description 6
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 6
- 239000003580 lung surfactant Substances 0.000 claims description 6
- 125000004505 1,2,4-oxadiazol-5-yl group Chemical group O1N=CN=C1* 0.000 claims description 5
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 5
- 229940124125 5 Lipoxygenase inhibitor Drugs 0.000 claims description 5
- 229930003316 Vitamin D Natural products 0.000 claims description 5
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims description 5
- 229940088710 antibiotic agent Drugs 0.000 claims description 5
- 230000006806 disease prevention Effects 0.000 claims description 5
- 239000002308 endothelin receptor antagonist Substances 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical group 0.000 claims description 5
- 239000000938 histamine H1 antagonist Substances 0.000 claims description 5
- 229960004617 sapropterin Drugs 0.000 claims description 5
- 239000011710 vitamin D Substances 0.000 claims description 5
- 235000019166 vitamin D Nutrition 0.000 claims description 5
- 150000003710 vitamin D derivatives Chemical class 0.000 claims description 5
- 229940046008 vitamin d Drugs 0.000 claims description 5
- 229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 claims description 4
- 229960001334 corticosteroids Drugs 0.000 claims description 4
- 229940082657 digitalis glycosides Drugs 0.000 claims description 4
- KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 claims description 4
- 229960001123 epoprostenol Drugs 0.000 claims description 4
- 229960003073 pirfenidone Drugs 0.000 claims description 4
- ISWRGOKTTBVCFA-UHFFFAOYSA-N pirfenidone Chemical compound C1=C(C)C=CC(=O)N1C1=CC=CC=C1 ISWRGOKTTBVCFA-UHFFFAOYSA-N 0.000 claims description 4
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 claims description 4
- 239000000021 stimulant Substances 0.000 claims description 4
- 125000001359 1,2,3-triazol-4-yl group Chemical group [H]N1N=NC([*])=C1[H] 0.000 claims description 3
- 125000001766 1,2,4-oxadiazol-3-yl group Chemical group [H]C1=NC(*)=NO1 0.000 claims description 3
- 125000001305 1,2,4-triazol-3-yl group Chemical group [H]N1N=C([*])N=C1[H] 0.000 claims description 3
- 125000004509 1,3,4-oxadiazol-2-yl group Chemical group O1C(=NN=C1)* 0.000 claims description 3
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 claims description 3
- 125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 0.000 claims description 3
- 125000004498 isoxazol-4-yl group Chemical group O1N=CC(=C1)* 0.000 claims description 3
- 125000004499 isoxazol-5-yl group Chemical group O1N=CC=C1* 0.000 claims description 3
- 125000004289 pyrazol-3-yl group Chemical group [H]N1N=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000004521 1,3,4-thiadiazol-2-yl group Chemical group S1C(=NN=C1)* 0.000 claims description 2
- SUCDHPJUXCCMDN-UHFFFAOYSA-N 2-ethyl-1,3-oxazole Chemical group CCC1=NC=CO1 SUCDHPJUXCCMDN-UHFFFAOYSA-N 0.000 claims description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 2
- 230000036039 immunity Effects 0.000 claims 2
- 125000004515 1,2,4-thiadiazol-3-yl group Chemical group S1N=C(N=C1)* 0.000 claims 1
- 125000004516 1,2,4-thiadiazol-5-yl group Chemical group S1N=CN=C1* 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 528
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 186
- 239000007787 solid Substances 0.000 description 178
- 239000000243 solution Substances 0.000 description 169
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 138
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 132
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 105
- 238000006243 chemical reaction Methods 0.000 description 102
- 238000000034 method Methods 0.000 description 102
- 239000000203 mixture Substances 0.000 description 101
- 239000000741 silica gel Substances 0.000 description 100
- 229910002027 silica gel Inorganic materials 0.000 description 100
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 96
- 238000003818 flash chromatography Methods 0.000 description 95
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 92
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 87
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 69
- 238000010828 elution Methods 0.000 description 68
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 65
- 239000011541 reaction mixture Substances 0.000 description 63
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 62
- 238000000746 purification Methods 0.000 description 61
- 239000002904 solvent Substances 0.000 description 61
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 58
- 239000012071 phase Substances 0.000 description 57
- 239000000725 suspension Substances 0.000 description 57
- UZKBSZSTDQSMDR-UHFFFAOYSA-N 1-[(4-chlorophenyl)-phenylmethyl]piperazine Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC=CC=1)N1CCNCC1 UZKBSZSTDQSMDR-UHFFFAOYSA-N 0.000 description 53
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 51
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 49
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 49
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
- 229910000027 potassium carbonate Inorganic materials 0.000 description 46
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 42
- 230000002829 reductive effect Effects 0.000 description 42
- 239000003480 eluent Substances 0.000 description 40
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 36
- 238000002953 preparative HPLC Methods 0.000 description 31
- UXIZVOHYPKZDGA-QZTJIDSGSA-N 4-[(4ar,10br)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1h-thiopyrano[4,3-c]isoquinolin-6-yl]benzoic acid Chemical compound N([C@@H]1CCSC[C@@H]1C=1C=C(C(=CC=11)OC)OCC)=C1C1=CC=C(C(O)=O)C=C1 UXIZVOHYPKZDGA-QZTJIDSGSA-N 0.000 description 30
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 30
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 30
- 238000003756 stirring Methods 0.000 description 29
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 28
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- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 11
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- AHIUOMGSUBQPIJ-QZTJIDSGSA-N 3-[(4ar,10br)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1h-thiopyrano[4,3-c]isoquinolin-6-yl]benzoic acid Chemical compound N([C@@H]1CCSC[C@@H]1C=1C=C(C(=CC=11)OC)OCC)=C1C1=CC=CC(C(O)=O)=C1 AHIUOMGSUBQPIJ-QZTJIDSGSA-N 0.000 description 10
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- FPQVGDGSRVMNMR-JCTPKUEWSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-(dimethylamino)methylidene]-dimethylazanium;tetrafluoroborate Chemical compound F[B-](F)(F)F.CCOC(=O)C(\C#N)=N/OC(N(C)C)=[N+](C)C FPQVGDGSRVMNMR-JCTPKUEWSA-N 0.000 description 8
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- 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 8
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| EP2577777B1 (en) | 2010-06-07 | 2016-12-28 | Sapurast Research LLC | Rechargeable, high-density electrochemical device |
| RU2013142268A (ru) * | 2011-02-17 | 2015-03-27 | Сипла Лимитед | Фармацевтическая композиция |
| EP2721036B1 (en) | 2011-06-15 | 2015-07-22 | Takeda GmbH | Novel 3,4,4a,10b-tetrahydro-1h-thiopyrano[4,3-c]isoquinoline compounds |
| WO2014016548A2 (en) * | 2012-07-27 | 2014-01-30 | Cipla Limited | Pharmaceutical composition |
| US20150322049A1 (en) * | 2012-12-13 | 2015-11-12 | Ludwig Aigner | Leukotriene pathway antagonists for the treatment of dementia, cognitive deficits in parkinson's disease and/or learning and memory deficiencies in parkinson's disease |
| EP2951161A1 (en) | 2013-02-04 | 2015-12-09 | Grünenthal GmbH | 4-amino substituted condensed pyrimidine compounds as pde4 inhibitors |
| MD20150071A2 (ro) | 2013-02-19 | 2016-02-29 | Pfizer Inc. | Compuşi azabenzimidazolici ca inhibitori ai PDE4 izoenzimelor pentru tratamentul tulburărilor SNC şi altor afecţiuni |
| US10131669B2 (en) | 2014-07-24 | 2018-11-20 | Pfizer Inc. | Pyrazolopyrimidine compounds |
| HUE044040T2 (hu) | 2014-08-06 | 2019-09-30 | Pfizer | Imidazopiridazin vegyületek |
| WO2017089347A1 (en) | 2015-11-25 | 2017-06-01 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Methods and pharmaceutical compositions for the treatment of braf inhibitor resistant melanomas |
| US12383547B2 (en) | 2020-07-01 | 2025-08-12 | Vanderbilt University | Methods of treatment for a kidney disease |
Family Cites Families (38)
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| DE4003272A1 (de) | 1990-02-03 | 1991-08-08 | Boehringer Ingelheim Kg | Neue treibgasmischungen und ihre verwendung in arzneimittelzubereitungen |
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| CA2288789C (en) | 1997-05-08 | 2009-07-21 | Merck Sharp & Dohme Limited | Substituted 1,2,4-triazolo[3,4-a]phthalazine derivatives as gaba alpha 5 ligands |
| AU8106598A (en) | 1997-06-03 | 1998-12-21 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Benzonaphthyridine |
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| US6397838B1 (en) | 1998-12-23 | 2002-06-04 | Battelle Pulmonary Therapeutics, Inc. | Pulmonary aerosol delivery device and method |
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| BR0009993A (pt) | 1999-04-23 | 2002-01-08 | Battelle Memorial Institute | Pulverizador de aerossol eletrohidrodinâmico direcionalmente controlado, dispositivo para liberar gotìculas de aerossol eletricamente neutras, aparelho para liberar gotìculas de aerossol terapêuticas, processo para liberar gotìculas de aerossol, e, dispositivo para liberar aerossol |
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| GB0202254D0 (en) | 2002-01-31 | 2002-03-20 | Pfizer Ltd | Prevention of scarring |
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| EP1755589A4 (en) | 2004-04-23 | 2007-11-07 | Celgene Corp | METHOD OF USING PDE4 MODULATORS AND COMPOSITIONS COMPRISING THEM FOR THE TREATMENT AND MANAGEMENT OF PULMONARY HYPERTENSION |
| EP1791847A2 (en) | 2004-09-08 | 2007-06-06 | Altana Pharma AG | Novel 3-thia-10-aza-phenanthrene derivatives |
| DE602005027866D1 (de) * | 2004-09-08 | 2011-06-16 | Nycomed Gmbh | 3-oxa-10-aza-phenanthrene als pde4- oder pde3/4-inhibitoren |
| JP4943858B2 (ja) | 2004-11-17 | 2012-05-30 | キッセイ薬品工業株式会社 | 芳香族アミド誘導体、それを含有する医薬組成物およびそれらの医薬用途 |
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| WO2008128647A1 (en) * | 2007-04-23 | 2008-10-30 | Sanofi-Aventis | Quinoline-carboxamide derivatives as p2y12 antagonists |
| EP2721036B1 (en) * | 2011-06-15 | 2015-07-22 | Takeda GmbH | Novel 3,4,4a,10b-tetrahydro-1h-thiopyrano[4,3-c]isoquinoline compounds |
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