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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- 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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- Nitrogen Condensed Heterocyclic Rings (AREA)
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| 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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| EP3181566A1 (en) * | 2010-09-20 | 2017-06-21 | Ironwood Pharmaceuticals, Inc. | Imidazotriazinone compounds |
| MX381326B (es) * | 2011-10-10 | 2025-03-12 | H Lundbeck As | Derivados de 7h-imidazo[1-5-a]pirazin-8-ona como inhibidores de la fosfodiesterasa 9(pde9); y el uso de los mismos en el tratamiento de trastornos neurodegenerativos |
| EP2807163B1 (en) * | 2012-01-26 | 2017-03-22 | H. Lundbeck A/S | Pde9 inhibitors with imidazo triazinone backbone |
| EP2828262A4 (en) | 2012-03-19 | 2015-09-23 | Forum Pharmaceuticals Inc | IMIDAZOTRIAZINONVERBINDUNGEN |
| 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 |
| WO2014024125A1 (en) | 2012-08-08 | 2014-02-13 | Celon Pharma S.A. | Pyrazolo[4,3-d]pyrimidin-7(6h)-one derivatives as pde9 inhibitors |
| US20150284380A1 (en) | 2012-10-31 | 2015-10-08 | Bayer Cropscience Ag | Novel heterocyclic compounds as pest control agents |
| 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 |
| JP2018508555A (ja) * | 2015-03-16 | 2018-03-29 | 大日本住友製薬株式会社 | 二環性イミダゾロ誘導体 |
| TW201643167A (zh) * | 2015-04-22 | 2016-12-16 | Ｈ 朗德貝克公司 | 作爲ｐｄｅ１抑制劑之咪唑並三酮 |
| JO3627B1 (ar) | 2015-04-30 | 2020-08-27 | H Lundbeck As | إيميدازو بيرازينونات على هيئة مثبطات pde1 |
| CA2990521C (en) | 2015-07-07 | 2023-10-10 | H. Lundbeck A/S | Pde9 inhibitors with imidazo triazinone backbone and imidazo pyrazinone backbone for treatment of peripheral diseases |
| 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 |
| IL295973A (en) | 2016-07-06 | 2022-10-01 | H Lundbeck As | pde9 inhibitors for the treatment of peripheral diseases |
| US10633382B2 (en) | 2016-10-18 | 2020-04-28 | H. Lundbeck A/S | Imidazopyrazinones, pyrazolopyrimidinones and pyrazolopyridinones as PDE1 inhibitors |
| RU2019108717A (ru) | 2016-10-28 | 2020-11-30 | Х. Лундбекк А/С | Комбинированные средства для лечения, предусматривающего введение имидазопиразинонов |
| LT3532064T (lt) | 2016-10-28 | 2020-09-25 | H. Lundbeck A/S | Kompleksiniai gydymai, apimantys imidazopirazonus, skirti psichiatrinių ir (arba) kognityvinių sutrikimų gydymui |
| HUE065158T2 (hu) * | 2017-05-26 | 2024-05-28 | Cardurion Pharmaceuticals Inc | PDE9 gátlószereinek elõállítására és alkalmazására szolgáló eljárások |
| BR112020024019A2 (pt) | 2018-05-25 | 2021-02-23 | Imara Inc. | monoidrato e formas cristalinas de 6-[(3s,4s)-4-metil-1-(pirimidin-2-ilmetil)pirrolidin-3-il]-3-tetra-hidropiran-4-il-7h-imidazo[1,5-a]pirazin-8-ona |
| KR20250108770A (ko) | 2018-08-31 | 2025-07-15 | 카듀리온 파마슈티칼스, 인크. | 겸상 세포 질환의 치료를 위한 pde9 억제제 |
| WO2020102374A1 (en) * | 2018-11-14 | 2020-05-22 | 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 |
| CA3155013A1 (en) * | 2019-10-21 | 2021-04-29 | Ki Ho Lee | Use of imidazopyrimidine or imidazotriazine compound for prevention, alleviation, or treatment of developmental disability |
| 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 |
| DE19750085A1 (de) * | 1997-11-12 | 1999-05-20 | Bayer Ag | 2-Phenyl-substituierte Imidazotriazinone |
| HU227841B1 (en) | 1997-11-12 | 2012-05-02 | Bayer Pharma AG | 2-phenyl substituted imidazotriazinones, process for their preparation and pharmaceutical compositions thereof |
| 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 |
| KR20040053210A (ko) * | 2001-11-02 | 2004-06-23 | 화이자 프로덕츠 인크. | Ｐｄｅ9 억제제를 사용한 인슐린 저항 증후군 및 2형당뇨병의 치료 |
| WO2004078163A2 (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 |
| DE10229778A1 (de) * | 2002-07-03 | 2004-01-29 | Bayer Ag | Neue Verwendung von Imidazotriazinonen |
| 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 |
| US20090163521A1 (en) | 2005-06-28 | 2009-06-25 | Orchid Research Laboratories Limited | Novel Pyrazolopyrimidinone Derivatives |
| PT2152712E (pt) * | 2007-05-11 | 2012-02-29 | Pfizer | Compostos amino-heterocíclicos |
| CN102131801B (zh) | 2008-06-25 | 2015-04-08 | 福拉姆医药股份有限公司 | 1,2-二取代的杂环化合物 |
| EP3181566A1 (en) | 2010-09-20 | 2017-06-21 | Ironwood Pharmaceuticals, Inc. | Imidazotriazinone compounds |
| EP2807163B1 (en) | 2012-01-26 | 2017-03-22 | H. Lundbeck A/S | Pde9 inhibitors with imidazo triazinone backbone |
| EP2828262A4 (en) | 2012-03-19 | 2015-09-23 | Forum Pharmaceuticals Inc | IMIDAZOTRIAZINONVERBINDUNGEN |
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- 2011-09-20 AU AU2011305568A patent/AU2011305568B2/en not_active Ceased
- 2011-09-20 CA CA2811714A patent/CA2811714C/en not_active Expired - Fee Related
- 2011-09-20 MX MX2013003093A patent/MX2013003093A/es active IP Right Grant
- 2011-09-20 US US13/237,795 patent/US20120157458A1/en not_active Abandoned
- 2011-09-20 PL PL11761793T patent/PL2619208T3/pl unknown
- 2011-09-20 WO PCT/US2011/052399 patent/WO2012040230A1/en not_active Ceased
- 2011-09-20 TW TW100133825A patent/TWI541244B/zh not_active IP Right Cessation
- 2011-09-20 UY UY0001033616A patent/UY33616A/es unknown
- 2011-09-20 AR ARP110103426A patent/AR083058A1/es unknown
- 2011-09-20 DK DK11761793.6T patent/DK2619208T3/en active
- 2011-09-20 CN CN201180055157.9A patent/CN103313988B/zh not_active Expired - Fee Related
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2014
- 2014-07-17 US US14/334,073 patent/US9540380B2/en not_active Expired - Fee Related
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2015
- 2015-12-08 JP JP2015239514A patent/JP2016104747A/ja active Pending
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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 |
|---|---|
| AU2011305568B2 (en) | 2015-12-10 |
| US20170152265A1 (en) | 2017-06-01 |
| CN103313988A (zh) | 2013-09-18 |
| US20140330014A1 (en) | 2014-11-06 |
| TW201217381A (en) | 2012-05-01 |
| AR083058A1 (es) | 2013-01-30 |
| WO2012040230A1 (en) | 2012-03-29 |
| BR112013008140A2 (pt) | 2017-12-05 |
| CA2811714C (en) | 2017-11-21 |
| TWI541244B (zh) | 2016-07-11 |
| RU2603140C2 (ru) | 2016-11-20 |
| UY33616A (es) | 2012-04-30 |
| JP2016104747A (ja) | 2016-06-09 |
| HK1187908A1 (en) | 2014-04-17 |
| MX2013003093A (es) | 2013-10-28 |
| EP3181566A1 (en) | 2017-06-21 |
| EP2619208B1 (en) | 2016-11-09 |
| BR112013008140A8 (pt) | 2018-04-03 |
| CN103313988B (zh) | 2016-06-08 |
| DK2619208T3 (en) | 2017-01-30 |
| JP2013540755A (ja) | 2013-11-07 |
| EP2619208A1 (en) | 2013-07-31 |
| PL2619208T3 (pl) | 2017-03-31 |
| US20120157458A1 (en) | 2012-06-21 |
| JP5855109B2 (ja) | 2016-02-09 |
| CA2811714A1 (en) | 2012-03-29 |
| RU2013118362A (ru) | 2014-10-27 |
| AU2011305568A1 (en) | 2013-04-04 |
| US9540380B2 (en) | 2017-01-10 |
| AU2016200970A1 (en) | 2016-03-03 |
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