JP2008512346A5 - - Google Patents
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- JP2008512346A5 JP2008512346A5 JP2007511147A JP2007511147A JP2008512346A5 JP 2008512346 A5 JP2008512346 A5 JP 2008512346A5 JP 2007511147 A JP2007511147 A JP 2007511147A JP 2007511147 A JP2007511147 A JP 2007511147A JP 2008512346 A5 JP2008512346 A5 JP 2008512346A5
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- JP
- Japan
- Prior art keywords
- ethyl
- acetamide
- methyl
- nmr
- ppm
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 162
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 144
- 239000000243 solution Substances 0.000 description 139
- 150000001875 compounds Chemical class 0.000 description 127
- 238000005160 1H NMR spectroscopy Methods 0.000 description 118
- 238000000034 method Methods 0.000 description 117
- 238000004519 manufacturing process Methods 0.000 description 101
- 239000000203 mixture Substances 0.000 description 97
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 95
- 102100027159 Membrane primary amine oxidase Human genes 0.000 description 86
- -1 —OH Chemical group 0.000 description 85
- 101710132836 Membrane primary amine oxidase Proteins 0.000 description 84
- 230000008569 process Effects 0.000 description 74
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 71
- 239000011541 reaction mixture Substances 0.000 description 68
- 239000007787 solid Substances 0.000 description 68
- 230000002829 reductive effect Effects 0.000 description 64
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 55
- 239000003112 inhibitor Substances 0.000 description 49
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 48
- 238000002360 preparation method Methods 0.000 description 48
- 150000003839 salts Chemical class 0.000 description 46
- 229960001701 chloroform Drugs 0.000 description 44
- 201000010099 disease Diseases 0.000 description 44
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 44
- 125000000217 alkyl group Chemical group 0.000 description 43
- 238000003786 synthesis reaction Methods 0.000 description 41
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
- 230000015572 biosynthetic process Effects 0.000 description 38
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 37
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 35
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 34
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- 239000012299 nitrogen atmosphere Substances 0.000 description 33
- 239000000741 silica gel Substances 0.000 description 33
- 229910002027 silica gel Inorganic materials 0.000 description 33
- 206010012601 diabetes mellitus Diseases 0.000 description 31
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 31
- 238000003818 flash chromatography Methods 0.000 description 30
- 125000003118 aryl group Chemical group 0.000 description 28
- 239000002244 precipitate Substances 0.000 description 28
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 27
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 26
- 208000001344 Macular Edema Diseases 0.000 description 26
- 206010025415 Macular oedema Diseases 0.000 description 26
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- 239000000706 filtrate Substances 0.000 description 24
- 238000001914 filtration Methods 0.000 description 24
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 23
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 22
- 235000019341 magnesium sulphate Nutrition 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- 229910052739 hydrogen Inorganic materials 0.000 description 20
- 239000001257 hydrogen Substances 0.000 description 20
- 239000012044 organic layer Substances 0.000 description 20
- 239000011734 sodium Substances 0.000 description 20
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- 239000012267 brine Substances 0.000 description 19
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 19
- 208000024891 symptom Diseases 0.000 description 19
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- 125000004432 carbon atom Chemical group C* 0.000 description 16
- 238000001816 cooling Methods 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 235000017557 sodium bicarbonate Nutrition 0.000 description 15
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 15
- 208000017442 Retinal disease Diseases 0.000 description 14
- 206010038923 Retinopathy Diseases 0.000 description 14
- 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 14
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 13
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
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- 125000003710 aryl alkyl group Chemical group 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 11
- 239000000843 powder Substances 0.000 description 11
- 238000010898 silica gel chromatography Methods 0.000 description 11
- 125000001424 substituent group Chemical group 0.000 description 11
- 238000006467 substitution reaction Methods 0.000 description 11
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 10
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- 150000002431 hydrogen Chemical class 0.000 description 9
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- 238000003756 stirring Methods 0.000 description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
- 229920002554 vinyl polymer Polymers 0.000 description 9
- LSBXWMQLLHVMMW-UHFFFAOYSA-N 2-[5-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]thiophen-2-yl]-n-(diaminomethylidene)acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2SC(CC(=O)NC(N)=N)=CC=2)=C1 LSBXWMQLLHVMMW-UHFFFAOYSA-N 0.000 description 8
- 206010020772 Hypertension Diseases 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
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- 235000011054 acetic acid Nutrition 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
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- 150000002367 halogens Chemical class 0.000 description 8
- 125000000623 heterocyclic group Chemical group 0.000 description 8
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- 201000008482 osteoarthritis Diseases 0.000 description 8
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 8
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- 230000002792 vascular Effects 0.000 description 8
- ZEXMUXOCMYAHLH-UHFFFAOYSA-N 2-[4-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]phenyl]acetic acid Chemical compound S1C(NC(=O)C)=NC(CCC=2C=CC(CC(O)=O)=CC=2)=C1 ZEXMUXOCMYAHLH-UHFFFAOYSA-N 0.000 description 7
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- 206010047115 Vasculitis Diseases 0.000 description 7
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 7
- 125000002947 alkylene group Chemical group 0.000 description 7
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- WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 229910052736 halogen Inorganic materials 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- VXAPNCLMTSOGLM-UHFFFAOYSA-N n-[4-[2-[4-[(2-amino-1h-imidazol-5-yl)methyl]phenyl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2C=CC(CC=3N=C(N)NC=3)=CC=2)=C1 VXAPNCLMTSOGLM-UHFFFAOYSA-N 0.000 description 6
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| AU2004905183A AU2004905183A0 (en) | 2004-09-09 | Thiazole Derivatives Having VAP-1 Inhibitory Activity | |
| PCT/JP2005/016984 WO2006028269A2 (en) | 2004-09-09 | 2005-09-08 | Thiazole derivatives having vap-1 ihibitory activity |
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| JP2008512346A JP2008512346A (ja) | 2008-04-24 |
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| MX2008011791A (es) * | 2006-03-15 | 2008-09-25 | Wyeth Corp | Azaciclilaminas-n-sustituidas como antagonistas de histamina-3. |
| CN101784285B (zh) | 2007-06-25 | 2012-12-05 | 株式会社·R-技术上野 | 用于与低氧或局部缺血有关的眼科疾病的组合物 |
| CN103120690A (zh) | 2007-10-19 | 2013-05-29 | 株式会社·R-技术上野 | 用于治疗白内障的药物组合物 |
| TWI437986B (zh) * | 2008-01-31 | 2014-05-21 | R Tech Ueno Ltd | 噻唑衍生物及使用該衍生物作為ｖａｐ－１抑制劑之用途 |
| TWI490214B (zh) * | 2008-05-30 | 2015-07-01 | 艾德克 上野股份有限公司 | 苯或噻吩衍生物及該等作為ｖａｐ－１抑制劑之用途 |
| UA112154C2 (uk) | 2009-09-08 | 2016-08-10 | Біоті Терапіс Корп. | Застосування повністю людського анти-vap-1-антитіла для лікування фіброзних станів |
| FI20115234A0 (fi) | 2011-03-08 | 2011-03-08 | Biotie Therapies Corp | Uusia pyridatsinoni- ja pyridoniyhdisteitä |
| US20160113893A1 (en) | 2013-06-12 | 2016-04-28 | Proximagen Limited | New therapeutic uses of enzyme inhibitors |
| ES2714125T3 (es) | 2014-04-15 | 2019-05-27 | Pecsi Tudomanyegyetem | Inhibidores de la amino oxidasa sensible a la semicarbazida para uso como analgésicos en una neuropatía traumática y una inflamación neurogénica |
| MA49708A (fr) | 2014-04-30 | 2020-06-03 | Pfizer | Dérivés de dihétérocycle liés à cycloalkyle |
| WO2015189534A1 (en) | 2014-06-12 | 2015-12-17 | Proximagen Limited | Vap-1 inhibitors for treating muscular dystrophy |
| GB201506658D0 (en) | 2015-04-20 | 2015-06-03 | Cellcentric Ltd | Pharmaceutical compounds |
| GB201506660D0 (en) | 2015-04-20 | 2015-06-03 | Cellcentric Ltd | Pharmaceutical compounds |
| GB201507048D0 (en) * | 2015-04-24 | 2015-06-10 | Proximagen Ltd | Treatment of pain |
| JP2018076236A (ja) | 2015-06-05 | 2018-05-17 | 株式会社アールテック・ウエノ | がんを処置するための医薬組成物 |
| EP3386494A1 (en) | 2015-12-07 | 2018-10-17 | Benevolentai Cambridge Limited | Vap-1 inhibitors for treating pain |
| EP3423436B1 (en) * | 2016-03-03 | 2020-09-16 | Boehringer Ingelheim International GmbH | Pyridinylmethyl carbamimidoylcarbamate derivatives and their use as aoc3 inhibitors |
| WO2017148518A1 (en) * | 2016-03-03 | 2017-09-08 | Boehringer Ingelheim International Gmbh | 4-cyano-benzyl carbamimidoylcarbamate derivatives and their use as aoc3 inhibitors |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4699928A (en) * | 1984-07-13 | 1987-10-13 | Merrell Dow Pharmaceuticals Inc. | Fluoroallylamine derivatives |
| WO1986003203A1 (en) * | 1984-11-22 | 1986-06-05 | Yoshitomi Pharmaceutical Industries, Ltd. | Thienylthiazole derivatives |
| IT1181871B (it) * | 1985-04-01 | 1987-09-30 | Consiglio Nazionale Ricerche | Inibitori selettivi delle benzilamminossidasi rispetto ad altre amminossidasi |
| US4650907A (en) * | 1985-12-05 | 1987-03-17 | Merrell Dow Pharmaceuticals Inc. | Nonaromatic fluoroallylamine MAO inhibitors |
| US4916151A (en) * | 1985-12-05 | 1990-04-10 | Merrell Dow Pharmaceuticals Inc. | Method of treating parkinson's syndrome |
| DD261153A1 (de) * | 1987-03-19 | 1988-10-19 | Bitterfeld Chemie | Verfahren zur herstellung von neuen 2-heteroaryl-5-acylamino-thiazolen |
| US5021456A (en) * | 1988-02-25 | 1991-06-04 | Merrell Dow Pharmaceuticals Inc. | Inhibitors of lysyl oxidase |
| US5059714A (en) * | 1988-02-25 | 1991-10-22 | Merrell Dow Pharmaceuticals Inc. | Inhibitors of lysyl oxidase |
| US4965288A (en) * | 1988-02-25 | 1990-10-23 | Merrell Dow Pharmaceuticals Inc. | Inhibitors of lysyl oxidase |
| US4943593A (en) * | 1988-02-25 | 1990-07-24 | Merrell Dow Pharmaceuticals Inc. | Inhibitors of lysyl oxidase |
| AU2001282163B2 (en) * | 2000-07-05 | 2004-12-09 | Biotie Therapies Corp. | Inhibitors of copper-containing amine oxidases |
| CA2514573A1 (en) * | 2003-01-27 | 2004-08-12 | Astellas Pharma Inc. | Thiazole derivatives and their use as vap-1 inhibitors |
| TW200524575A (en) * | 2003-10-27 | 2005-08-01 | S Bio Pte Ltd | Biaryl linked hydroxamates: preparation and pharmaceutical applications |
-
2005
- 2005-09-08 CA CA002579889A patent/CA2579889A1/en not_active Abandoned
- 2005-09-08 WO PCT/JP2005/016984 patent/WO2006028269A2/en active Application Filing
- 2005-09-08 US US11/574,946 patent/US20080015202A1/en not_active Abandoned
- 2005-09-08 EP EP05783547A patent/EP1791835A2/en not_active Withdrawn
- 2005-09-08 JP JP2007511147A patent/JP2008512346A/ja not_active Abandoned
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