ES2610360T3 - Compuestos de imidazotriazinona - Google Patents
Compuestos de imidazotriazinona Download PDFInfo
- Publication number
- ES2610360T3 ES2610360T3 ES11761793.6T ES11761793T ES2610360T3 ES 2610360 T3 ES2610360 T3 ES 2610360T3 ES 11761793 T ES11761793 T ES 11761793T ES 2610360 T3 ES2610360 T3 ES 2610360T3
- Authority
- ES
- Spain
- Prior art keywords
- imidazo
- trans
- triazin
- mmol
- methylpyrrolidin
- 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.)
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- IJYHVZICHKCLMQ-UHFFFAOYSA-N imidazo[4,5-d]triazin-4-one Chemical class O=C1N=NN=C2N=CN=C12 IJYHVZICHKCLMQ-UHFFFAOYSA-N 0.000 title description 5
- 150000003839 salts Chemical class 0.000 claims abstract description 42
- 150000001875 compounds Chemical class 0.000 claims description 147
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 135
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- 101100407341 Drosophila melanogaster Pde9 gene Proteins 0.000 claims description 49
- 238000000034 method Methods 0.000 claims description 48
- QMNWYGTWTXOQTP-UHFFFAOYSA-N 1h-triazin-6-one Chemical compound O=C1C=CN=NN1 QMNWYGTWTXOQTP-UHFFFAOYSA-N 0.000 claims description 33
- 239000003814 drug Substances 0.000 claims description 28
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- 208000024827 Alzheimer disease Diseases 0.000 claims description 25
- 238000011282 treatment Methods 0.000 claims description 24
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 claims description 23
- 206010012289 Dementia Diseases 0.000 claims description 18
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- NIHUZJPITMUICY-UHFFFAOYSA-N 1h-imidazo[5,1-f][1,2,4]triazin-4-one Chemical compound O=C1NC=NN2C=NC=C12 NIHUZJPITMUICY-UHFFFAOYSA-N 0.000 abstract description 158
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 379
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 318
- -1 (pyrimidin-2-ylmethyl) pyrrolidin-3-yl Chemical group 0.000 description 290
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 195
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 178
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 153
- 239000000243 solution Substances 0.000 description 149
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 144
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 125
- 238000004809 thin layer chromatography Methods 0.000 description 105
- 238000005160 1H NMR spectroscopy Methods 0.000 description 103
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 95
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- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 55
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 55
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 54
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 54
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 50
- 230000002829 reductive effect Effects 0.000 description 49
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 48
- 239000012043 crude product Substances 0.000 description 48
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 47
- 239000013058 crude material Substances 0.000 description 45
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 44
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- 238000004296 chiral HPLC Methods 0.000 description 39
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- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 35
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- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 34
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 33
- ZHGNHOOVYPHPNJ-UHFFFAOYSA-N Amigdalin Chemical compound FC(F)(F)C(=O)OCC1OC(OCC2OC(OC(C#N)C3=CC=CC=C3)C(OC(=O)C(F)(F)F)C(OC(=O)C(F)(F)F)C2OC(=O)C(F)(F)F)C(OC(=O)C(F)(F)F)C(OC(=O)C(F)(F)F)C1OC(=O)C(F)(F)F ZHGNHOOVYPHPNJ-UHFFFAOYSA-N 0.000 description 33
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 31
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- 229910052736 halogen Inorganic materials 0.000 description 27
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- PGJLOGNVZGRMGX-UHFFFAOYSA-L iron(2+);trifluoromethanesulfonate Chemical compound [Fe+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F PGJLOGNVZGRMGX-UHFFFAOYSA-L 0.000 description 27
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- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
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- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
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| US38469410P | 2010-09-20 | 2010-09-20 | |
| US384694P | 2010-09-20 | ||
| PCT/US2011/052399 WO2012040230A1 (en) | 2010-09-20 | 2011-09-20 | Imidazotriazinone compounds |
Publications (1)
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| ES2610360T3 true ES2610360T3 (es) | 2017-04-27 |
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| ES11761793.6T Active ES2610360T3 (es) | 2010-09-20 | 2011-09-20 | Compuestos de imidazotriazinona |
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| AU2011305568B2 (en) | 2010-09-20 | 2015-12-10 | Ironwood Pharmaceuticals, Inc. | Imidazotriazinone compounds |
| CN106905324B (zh) * | 2011-10-10 | 2018-09-25 | H.隆德贝克有限公司 | 具有咪唑并吡嗪酮骨架的pde9抑制剂 |
| CN104093720B (zh) * | 2012-01-26 | 2017-04-12 | H.隆德贝克有限公司 | 具有咪唑并三嗪酮骨架的pde9抑制剂 |
| HK1206726A1 (en) | 2012-03-19 | 2016-01-15 | Ironwood Pharmaceuticals, Inc. | Imidazotriazinone compounds |
| WO2014024125A1 (en) | 2012-08-08 | 2014-02-13 | Celon Pharma S.A. | Pyrazolo[4,3-d]pyrimidin-7(6h)-one derivatives as pde9 inhibitors |
| CN102786525B (zh) | 2012-08-08 | 2014-12-17 | 中山大学 | N-取代吡唑并[3,4-d]嘧啶酮类化合物、其制备方法及其应用 |
| CN104884449A (zh) | 2012-10-31 | 2015-09-02 | 拜尔农作物科学股份公司 | 作为害虫防治剂的新的杂环化合物 |
| TW201629064A (zh) | 2014-10-10 | 2016-08-16 | Ｈ 朗德貝克公司 | 作爲ｐｄｅ１抑制劑之三唑並吡酮 |
| US20180044343A1 (en) * | 2015-03-16 | 2018-02-15 | Sumitomo Dainippon Pharma Co., Ltd. | Bicyclic imidazolo derivative |
| US20160311831A1 (en) * | 2015-04-22 | 2016-10-27 | H. Lundbeck A/S | Imidazotriazinones as PDE1 Inhibitors |
| JO3627B1 (ar) | 2015-04-30 | 2020-08-27 | H Lundbeck As | إيميدازو بيرازينونات على هيئة مثبطات pde1 |
| BR112018000254A2 (pt) | 2015-07-07 | 2018-09-04 | H Lundbeck As | inibidores de pde9 com cadeia principal de imidazotriazinona e cadeia principal de imidazopirazinona para o tratamento de doenças periféricas |
| WO2017070293A1 (en) * | 2015-10-20 | 2017-04-27 | Ironwood Pharmaceuticals, Inc. | Phosphodiesterase 9 inhibitor and levodopa therapy |
| CN105669680B (zh) * | 2016-03-24 | 2018-02-23 | 南京药捷安康生物科技有限公司 | 吡咯并[2,1‑f][1,2,4]三嗪‑4(1H)‑酮衍生物类PDE9A抑制剂 |
| TWI729109B (zh) | 2016-04-12 | 2021-06-01 | 丹麥商Ｈ 朗德貝克公司 | 作爲PDE1抑制劑的1,5-二氫-4H-吡唑并[3,4-d]嘧啶-4-酮和1,5-二氫-4H-吡唑并[4,3-c]吡啶-4-酮 |
| AU2017292650A1 (en) | 2016-07-06 | 2018-12-13 | H. Lundbeck A/S | PDE9 inhibitors for treatment of peripheral diseases |
| EP3529250B1 (en) | 2016-10-18 | 2023-12-06 | H. Lundbeck A/S | Imidazopyrazinones, pyrazolopyrimidinones and pyrazolopyridinones as pde1 inhibitors |
| SG11201903770UA (en) | 2016-10-28 | 2019-05-30 | H Lundbeck As | Combination treatments comprising imidazopyrazinones for the treatment of psychiatric and/or cognitive disorders |
| BR112018013084A2 (pt) | 2016-10-28 | 2018-12-11 | H Lundbeck As | tratamentos de combinação compreendendo a administração de imidazopirazinonas |
| SI3630772T1 (sl) | 2017-05-26 | 2024-05-31 | Cardurion Pharmaceuticals, Inc., | Postopki izdelave in uporabe zaviralcev pde9 |
| EP3801526B1 (en) | 2018-05-25 | 2023-12-27 | Imara Inc. | Monohydrate and crystalline forms of 6-[(3s,4s)-4-methyl-1- (pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-3-tetrahydropyran-4-yl- 7h-imid azo [1,5- a] pyrazin-8-one |
| CN112996512B (zh) | 2018-08-31 | 2025-01-03 | 卡都瑞恩医药公司 | 用于治疗镰状细胞病的pde9抑制剂 |
| US20220041667A1 (en) * | 2018-11-14 | 2022-02-10 | The Board Of Trustees Of The Leland Stanford Junior University | Targeting of makap-pde4d3 complexes in neurodegenerative disease |
| KR102712818B1 (ko) * | 2018-12-06 | 2024-09-30 | 한국화학연구원 | Pde9a 저해 활성을 가지는 화합물 및 이들의 의약 용도 |
| EP4049661A4 (en) * | 2019-10-21 | 2023-11-08 | SK Biopharmaceuticals Co., Ltd. | USE OF AN IMIDAZOPYRIMIDINE OR IMIDAZOTRIAZINE COMPOUND TO PREVENT, RELIEF OR TREAT DEVELOPMENTAL DISABILITIES |
| CN112724079A (zh) * | 2021-02-04 | 2021-04-30 | 康化（上海）新药研发有限公司 | 一种6-甲氧基吡啶甲酸甲酯的合成方法 |
| GB2632307A (en) * | 2023-08-02 | 2025-02-05 | Duke Street Bio Ltd | PARP1 inhibitor compounds |
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| PT72878B (en) | 1980-04-24 | 1983-03-29 | Merck & Co Inc | Process for preparing mannich-base hydroxamic acid pro-drugs for the improved delivery of non-steroidal anti-inflammatory agents |
| TR200001338T2 (tr) | 1997-11-12 | 2000-08-21 | Bayer Aktiengesellschaft | 2-Fenil-ikameli imidazotriazinonlar |
| DE19750085A1 (de) * | 1997-11-12 | 1999-05-20 | Bayer Ag | 2-Phenyl-substituierte Imidazotriazinone |
| GB0113343D0 (en) * | 2001-06-01 | 2001-07-25 | Bayer Ag | Novel Heterocycles 2 |
| US7087605B2 (en) | 2001-06-01 | 2006-08-08 | Bayer Aktiengesellschaft | 5-Ethyl-imidazotriazinones |
| JP2005508978A (ja) * | 2001-11-02 | 2005-04-07 | ファイザー・プロダクツ・インク | Ｐｄｅ９阻害薬によるインスリン抵抗性症候群及び２型糖尿病の治療 |
| DE10229778A1 (de) * | 2002-07-03 | 2004-01-29 | Bayer Ag | Neue Verwendung von Imidazotriazinonen |
| CA2514733A1 (en) | 2003-02-28 | 2004-09-16 | Transform Pharmaceuticals, Inc. | Pharmaceutical co-crystal compositions of drugs such as carbamazepine, celecoxib, olanzapine, itraconazole, topiramate, modafinil, 5-fluorouracil, hydrochlorothiazide, acetaminophen, aspirin, flurbiprofen, phenytoin and ibuprofen |
| US20040220186A1 (en) | 2003-04-30 | 2004-11-04 | Pfizer Inc. | PDE9 inhibitors for treating type 2 diabetes,metabolic syndrome, and cardiovascular disease |
| WO2006127368A2 (en) | 2005-05-20 | 2006-11-30 | Lexicon Genetics Incorporated | Methods for synthesizing imidazotriazinones |
| EP1896476A2 (en) | 2005-06-28 | 2008-03-12 | Orchid Research Laboratories Limited | Novel pyrazolopyrimidinone derivatives |
| MX2009011830A (es) * | 2007-05-11 | 2009-11-13 | Pfizer | Compuestos amino-heterociclicos. |
| BRPI0914772A2 (pt) | 2008-06-25 | 2015-10-20 | Envivo Pharmaceuticals Inc | compostos heterocíclicos 1,2-dissubstituídos |
| AU2011305568B2 (en) | 2010-09-20 | 2015-12-10 | Ironwood Pharmaceuticals, Inc. | Imidazotriazinone compounds |
| CN104093720B (zh) | 2012-01-26 | 2017-04-12 | H.隆德贝克有限公司 | 具有咪唑并三嗪酮骨架的pde9抑制剂 |
| HK1206726A1 (en) | 2012-03-19 | 2016-01-15 | Ironwood Pharmaceuticals, Inc. | Imidazotriazinone compounds |
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- 2011-09-20 WO PCT/US2011/052399 patent/WO2012040230A1/en not_active Ceased
- 2011-09-20 US US13/237,795 patent/US20120157458A1/en not_active Abandoned
- 2011-09-20 DK DK11761793.6T patent/DK2619208T3/en active
- 2011-09-20 CA CA2811714A patent/CA2811714C/en not_active Expired - Fee Related
- 2011-09-20 JP JP2013530234A patent/JP5855109B2/ja not_active Expired - Fee Related
- 2011-09-20 TW TW100133825A patent/TWI541244B/zh not_active IP Right Cessation
- 2011-09-20 BR BR112013008140A patent/BR112013008140A8/pt not_active IP Right Cessation
- 2011-09-20 UY UY0001033616A patent/UY33616A/es unknown
-
2014
- 2014-07-17 US US14/334,073 patent/US9540380B2/en not_active Expired - Fee Related
-
2015
- 2015-12-08 JP JP2015239514A patent/JP2016104747A/ja active Pending
-
2016
- 2016-02-16 AU AU2016200970A patent/AU2016200970A1/en not_active Abandoned
- 2016-12-07 US US15/371,935 patent/US20170152265A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| DK2619208T3 (en) | 2017-01-30 |
| BR112013008140A2 (pt) | 2017-12-05 |
| AR083058A1 (es) | 2013-01-30 |
| EP3181566A1 (en) | 2017-06-21 |
| RU2603140C2 (ru) | 2016-11-20 |
| JP5855109B2 (ja) | 2016-02-09 |
| UY33616A (es) | 2012-04-30 |
| CN103313988A (zh) | 2013-09-18 |
| US20140330014A1 (en) | 2014-11-06 |
| EP2619208B1 (en) | 2016-11-09 |
| CN103313988B (zh) | 2016-06-08 |
| AU2011305568A1 (en) | 2013-04-04 |
| US20120157458A1 (en) | 2012-06-21 |
| TW201217381A (en) | 2012-05-01 |
| CA2811714A1 (en) | 2012-03-29 |
| BR112013008140A8 (pt) | 2018-04-03 |
| PL2619208T3 (pl) | 2017-03-31 |
| TWI541244B (zh) | 2016-07-11 |
| EP2619208A1 (en) | 2013-07-31 |
| RU2013118362A (ru) | 2014-10-27 |
| CA2811714C (en) | 2017-11-21 |
| AU2016200970A1 (en) | 2016-03-03 |
| US20170152265A1 (en) | 2017-06-01 |
| WO2012040230A1 (en) | 2012-03-29 |
| JP2016104747A (ja) | 2016-06-09 |
| JP2013540755A (ja) | 2013-11-07 |
| US9540380B2 (en) | 2017-01-10 |
| HK1187908A1 (en) | 2014-04-17 |
| AU2011305568B2 (en) | 2015-12-10 |
| MX2013003093A (es) | 2013-10-28 |
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