ES2895487T3 - Método de preparación de un inhibidor de la PDE10 ópticamente activo - Google Patents
Método de preparación de un inhibidor de la PDE10 ópticamente activo Download PDFInfo
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- ES2895487T3 ES2895487T3 ES15785340T ES15785340T ES2895487T3 ES 2895487 T3 ES2895487 T3 ES 2895487T3 ES 15785340 T ES15785340 T ES 15785340T ES 15785340 T ES15785340 T ES 15785340T ES 2895487 T3 ES2895487 T3 ES 2895487T3
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Classifications
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- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
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- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Veterinary Medicine (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
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- Psychology (AREA)
- Epidemiology (AREA)
- Anesthesiology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (3)
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| US201461985381P | 2014-04-28 | 2014-04-28 | |
| US201462047569P | 2014-09-08 | 2014-09-08 | |
| PCT/US2015/027645 WO2015167968A1 (en) | 2014-04-28 | 2015-04-24 | Optically active pde10 inhibitor |
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| ES2895487T3 true ES2895487T3 (es) | 2022-02-21 |
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| PL2544679T3 (pl) * | 2010-03-12 | 2019-10-31 | Omeros Corp | Inhibitory PDE10 oraz powiązane kompozycje i sposoby |
| NZ716462A (en) * | 2014-04-28 | 2017-11-24 | Omeros Corp | Optically active pde10 inhibitor |
| NZ716494A (en) * | 2014-04-28 | 2017-07-28 | Omeros Corp | Processes and intermediates for the preparation of a pde10 inhibitor |
| US20160284909A1 (en) * | 2015-03-27 | 2016-09-29 | Gabriel Harley | Multi-diode solar cells |
| CA2980801A1 (en) * | 2015-04-24 | 2016-10-27 | Omeros Corporation | Pde10 inhibitors and related compositions and methods |
| US9920045B2 (en) | 2015-11-04 | 2018-03-20 | Omeros Corporation | Solid state forms of a PDE10 inhibitor |
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| PT100905A (pt) | 1991-09-30 | 1994-02-28 | Eisai Co Ltd | Compostos heterociclicos azotados biciclicos contendo aneis de benzeno, ciclo-hexano ou piridina e de pirimidina, piridina ou imidazol substituidos e composicoes farmaceuticas que os contem |
| RU95113454A (ru) | 1992-12-02 | 1997-06-10 | Пфайзер Инк. (US) | Катехольные диэфиры как селективные ингибиторы фдэiv, фармацевтическая композиция, способы лечения |
| DE4323192A1 (de) | 1993-07-10 | 1995-01-12 | Basf Ag | Verfahren zur Herstellung von Homo- und Copolymerisaten von Alk-1-enen |
| DE4325846C1 (de) | 1993-07-31 | 1995-01-19 | Herberts Gmbh | Verwendung von Furan-modifizierten aromatischen Pinakolderivaten als Initiatoren und Furan-modifizierte aromatische Pinakolderivate als solche |
| DE4343286A1 (de) | 1993-12-17 | 1995-06-22 | Hoechst Ag | Heteroaromatische Verbindungen und ihre Verwendung in flüssigkristallinen Mischungen |
| DE4409501A1 (de) | 1994-03-19 | 1995-09-21 | Didier Werke Ag | Verschleißfutter eines Schachtofens und Stein hierfür |
| AU695230B2 (en) | 1994-06-24 | 1998-08-06 | Euro-Celtique S.A. | Compounds for and method of inhibiting phosphodiesterase IV |
| US5789434A (en) | 1994-11-15 | 1998-08-04 | Bayer Corporation | Derivatives of substituted 4-biarylbutyric acid as matrix metalloprotease inhibitors |
| TW332201B (en) | 1995-04-06 | 1998-05-21 | Janssen Pharmaceutica Nv | 1,3-Dihydro-1-(phenylalkyl)-2H-imidazol-2-one derivatives |
| TW424087B (en) | 1995-04-06 | 2001-03-01 | Janssen Pharmaceutica Nv | 1,3-dihydro-1-(phenylalkenyl)-2H-imidazol-2-one derivatives |
| US6037370A (en) | 1995-06-08 | 2000-03-14 | Vertex Pharmaceuticals Incorporated | Methods and compositions for stimulating neurite growth |
| EA199800650A1 (ru) | 1996-01-22 | 1999-02-25 | Фудзисава, Фармасьютикал Ко., Лтд | Новые соединения |
| AU4015497A (en) | 1996-08-26 | 1998-03-19 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Thiazole derivatives useful as selective inhibitors of pde-iv |
| JPH1087543A (ja) | 1996-09-17 | 1998-04-07 | Chisso Corp | アルコキシベンゼン誘導体、液晶組成物および液晶表示素子 |
| US6548490B1 (en) | 1997-10-28 | 2003-04-15 | Vivus, Inc. | Transmucosal administration of phosphodiesterase inhibitors for the treatment of erectile dysfunction |
| WO1999045914A1 (en) | 1998-03-13 | 1999-09-16 | Maruho Kabushikikaisha | Alkyl amine derivative and local anesthetic agent using the same |
| GB9807354D0 (en) * | 1998-04-07 | 1998-06-03 | Glaxo Group Ltd | Antiviral compound |
| SE9804212D0 (sv) | 1998-12-04 | 1998-12-04 | Astra Pharma Prod | Compounds |
| WO2000034251A1 (en) | 1998-12-07 | 2000-06-15 | Smithkline Beecham Corporation | A method for quantitative determination of amino acids |
| SI1165516T1 (sl) | 1999-03-12 | 2005-02-28 | Boehringer Ingelheim Pharmaceuticals Inc. | Heterociklična sečnina in sorodne spojine, uporabne kot protivnetna sredstva |
| US7141593B1 (en) * | 1999-06-04 | 2006-11-28 | Abbott Laboratories | Pharmaceutical formulations |
| GB9929552D0 (en) | 1999-12-14 | 2000-02-09 | Proteus Molecular Design | Compounds |
| WO2001096334A2 (en) | 2000-06-15 | 2001-12-20 | Pharmacia Corporation | Heteroarylalkanoic acids as integrin receptor antagonists |
| US20030032579A1 (en) | 2001-04-20 | 2003-02-13 | Pfizer Inc. | Therapeutic use of selective PDE10 inhibitors |
| JP2004530703A (ja) * | 2001-05-22 | 2004-10-07 | ファイザー・プロダクツ・インク | 結晶形アジスロマイシン |
| US6821502B2 (en) * | 2002-06-12 | 2004-11-23 | Chevron U.S.A. Inc. | Method of making aluminum-containing zeolite with IFR structure |
| WO2004011410A1 (en) | 2002-07-27 | 2004-02-05 | Astrazeneca Ab | Chemical compounds |
| MXPA05003762A (es) | 2002-10-08 | 2005-07-22 | Scripps Research Inst | Inhibidores de hidrolasa de amida de acido graso. |
| WO2004041258A2 (fr) | 2002-10-30 | 2004-05-21 | Neuro3D | Utilisation d’inhibiteurs des phosphodiesterases des nucleotides cycliques, ayant une structure benzodiazepinique en therapie |
| TW200410921A (en) | 2002-11-25 | 2004-07-01 | Hoffmann La Roche | Mandelic acid derivatives |
| EP1568691A4 (en) | 2002-12-06 | 2010-08-25 | Kowa Co | ACCELERATOR FOR ERYTHROPOETIN PRODUCTION |
| MXPA05006727A (es) | 2002-12-20 | 2005-09-08 | Pharmacia Corp | Acidos heteroarilalcanoicos como antagonistas de receptor de integrina. |
| WO2004071509A1 (ja) | 2003-02-12 | 2004-08-26 | Nippon Chemiphar Co., Ltd. | オリゴデンドロサイト分化促進剤 |
| AU2004232973A1 (en) | 2003-04-18 | 2004-11-04 | Memory Pharmaceuticals Corporation | Pyrazole derivatives as phosphodiesterase 4 inhibitors |
| AR047541A1 (es) * | 2004-02-13 | 2006-01-25 | Sandoz Ag | Fosfato de 5-[[4-[2-metil-2-piridinil-amino-etoxi]fenil]metil]-2,4 tiazolidinadiona (rosiglitazona) y sus formas polimorficas |
| NZ550114A (en) | 2004-04-20 | 2011-02-25 | Transtech Pharma Inc | Substituted thiazole and pyrimidine derivatives as melanocortin receptor modulators |
| US20060074102A1 (en) | 2004-05-14 | 2006-04-06 | Kevin Cusack | Kinase inhibitors as therapeutic agents |
| US7351833B2 (en) * | 2004-07-23 | 2008-04-01 | Abbott Laboratories | (1S,5S)-3-(5,6-dichloropyridin-3-yl)-3,6-diazabicyclo[3.2.0]heptane benzenesulfonate |
| US7449486B2 (en) | 2004-10-19 | 2008-11-11 | Array Biopharma Inc. | Mitotic kinesin inhibitors and methods of use thereof |
| US8436176B2 (en) * | 2004-12-30 | 2013-05-07 | Medicis Pharmaceutical Corporation | Process for preparing 2-methyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine |
| UA86283C2 (uk) | 2005-01-07 | 2009-04-10 | Пфайзер Продактс Инк. | Гетероароматичні сполуки хіноліну і їх застосування як інгібіторів pde10 |
| EP1850681B1 (en) | 2005-02-04 | 2019-12-18 | Firmenich Incorporated | Compounds comprising linked hetero aryl moieties and their use as novel umami flavor modifiers, tastants and taste enhancers for comestible compositions |
| US20060252807A1 (en) | 2005-04-22 | 2006-11-09 | Kalypsys, Inc. | Novel ortho-terphenyl inhibitors of p38 kinase and methods of treating inflammatory disorders |
| UA91546C2 (uk) * | 2005-05-03 | 2010-08-10 | Бьорінгер Інгельхайм Інтернаціональ Гмбх | КРИСТАЛІЧНА ФОРМА 1-ХЛОР-4-(β-D-ГЛЮКОПІРАНОЗ-1-ИЛ)-2-[4-((S)-ТЕТРАГІДРОФУРАН-3-ІЛОКСИ)-БЕНЗИЛ]-БЕНЗОЛУ, СПОСІБ ЇЇ ОДЕРЖАННЯ ТА ЇЇ ЗАСТОСУВАННЯ ПРИ ПРИГОТУВАННІ ЛІКАРСЬКИХ ЗАСОБІВ |
| MY152185A (en) * | 2005-06-10 | 2014-08-29 | Novartis Ag | Modified release 1-[(3-hydroxy-adamant-1-ylamino)-acetyl]-pyrrolidine-2(s)-carbonitrile formulation |
| EP1928848A2 (en) | 2005-08-04 | 2008-06-11 | Apogee Biothechnology Corporation | Sphingosine kinase inhibitors and methods of their use |
| KR20080050577A (ko) * | 2005-08-29 | 2008-06-09 | 사노피-아벤티스 유.에스. 엘엘씨 | 피리다지노[4,5-ｂ]인돌 유도체의 신규 결정질 형태 |
| US7642246B2 (en) * | 2005-09-13 | 2010-01-05 | Sicor Inc. | Pure rocuronium bromide |
| SI1954684T1 (sl) | 2005-11-15 | 2014-07-31 | Otsuka Pharmaceutical Co., Ltd. | Oksazolna spojina in farmacevtski sestavek |
| EP1968946A4 (en) | 2005-12-23 | 2010-05-05 | Astrazeneca Ab | IMIDAZOLE AS MODULATORS OF THE GABA B RECEPTOR |
| JP2009535394A (ja) | 2006-05-02 | 2009-10-01 | ファイザー・プロダクツ・インク | Ｐｄｅ１０阻害剤としての二環式ヘテロアリール化合物 |
| US20080090834A1 (en) | 2006-07-06 | 2008-04-17 | Pfizer Inc | Selective azole pde10a inhibitor compounds |
| US20080234345A1 (en) | 2006-09-08 | 2008-09-25 | Gene Logic Inc. | Method for reducing or alleviating inflammation in the digestive tract |
| SG185979A1 (en) | 2006-09-25 | 2012-12-28 | Ptc Therapeutics Inc | Crystalline forms of 3-[5-(2-fluorophenyl)-[1,2,4]oxadiazol-3-yl]-benzoic acid |
| EP2079462A4 (en) * | 2006-09-28 | 2009-12-02 | Merck & Co Inc | PHARMACEUTICAL COMPOSITIONS OF HDAC INHIBITORS AND CHELABLE METAL COMPOUNDS AND METALO HDAC HEMMER CHELATE COMPLEXES |
| WO2008040669A2 (en) | 2006-10-02 | 2008-04-10 | Janssen Pharmaceutica N.V. | Novel intermediates for the preparation of a glyt1 inhibitor |
| US7837978B2 (en) * | 2006-10-13 | 2010-11-23 | Chevron U.S.A. Inc. | Process for preparing aluminum-containing molecular sieve SSZ-26 |
| US7786139B2 (en) | 2006-11-21 | 2010-08-31 | Omeros Corporation | PDE10 inhibitors and related compositions and methods |
| ES2624791T3 (es) | 2006-11-21 | 2017-07-17 | Omeros Corporation | Inhibidores de PDE10 y composiciones y métodos relacionados |
| PE20081506A1 (es) * | 2006-12-12 | 2008-12-09 | Infinity Discovery Inc | Formulaciones de ansamicina |
| WO2009008906A2 (en) | 2007-02-06 | 2009-01-15 | The Trustees Of The University Of Pennsylvania | Therapeutic compounds for blocking dna synthesis of pox viruses |
| AU2008253803A1 (en) * | 2007-05-22 | 2008-11-27 | Ultimorphix Technolgies B.V. | Tenofovir disoproxil hemi-fumaric acid Co-crystal |
| EP2017264A1 (de) | 2007-07-16 | 2009-01-21 | Bayer Cropscience Ag | Substituierte Phenylpropargylverbindungen, Verfahren zu deren Herstellung und deren Verwendung als Herbizide und Pflanzenwachstumsregulatoren |
| WO2009049022A1 (en) | 2007-10-10 | 2009-04-16 | Ore Pharmaceuticals Inc. | Method for treatment of pancreatitis |
| TW200944520A (en) * | 2008-01-29 | 2009-11-01 | Glaxo Group Ltd | Spiro compounds as NPY Y5 receptor antagonists |
| WO2009143178A2 (en) | 2008-05-20 | 2009-11-26 | Omeros Corporation | Pde10 inhibitors and related compositions and methods |
| TWI501965B (zh) | 2008-06-20 | 2015-10-01 | Lundbeck & Co As H | 作為ｐｄｅ１０ａ酵素抑制劑之新穎苯基咪唑衍生物 |
| US8377930B2 (en) | 2008-08-05 | 2013-02-19 | Omeros Corporation | PDE10 inhibitors and related compositions and methods |
| PL2544679T3 (pl) * | 2010-03-12 | 2019-10-31 | Omeros Corp | Inhibitory PDE10 oraz powiązane kompozycje i sposoby |
| NZ716462A (en) * | 2014-04-28 | 2017-11-24 | Omeros Corp | Optically active pde10 inhibitor |
| NZ716494A (en) * | 2014-04-28 | 2017-07-28 | Omeros Corp | Processes and intermediates for the preparation of a pde10 inhibitor |
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- 2014-09-10 NZ NZ716462A patent/NZ716462A/en unknown
- 2014-09-10 NZ NZ630803A patent/NZ630803A/en unknown
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2015
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- 2015-04-24 BR BR112016024523-7A patent/BR112016024523B1/pt active IP Right Grant
- 2015-04-24 JP JP2016564604A patent/JP2017513913A/ja active Pending
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| IL248586B (en) | 2019-09-26 |
| US20170096420A1 (en) | 2017-04-06 |
| KR102558505B1 (ko) | 2023-07-21 |
| CA2946754C (en) | 2022-08-30 |
| US9493447B2 (en) | 2016-11-15 |
| CN106255690A (zh) | 2016-12-21 |
| AU2015253463A1 (en) | 2016-11-03 |
| US9850238B2 (en) | 2017-12-26 |
| EP3137461B1 (en) | 2021-08-11 |
| BR112016024523B1 (pt) | 2022-10-11 |
| RU2016146097A (ru) | 2018-05-30 |
| CN106255690B (zh) | 2020-07-17 |
| KR20160141845A (ko) | 2016-12-09 |
| WO2015167968A1 (en) | 2015-11-05 |
| NZ630803A (en) | 2016-03-31 |
| NZ716462A (en) | 2017-11-24 |
| AU2015253463B2 (en) | 2018-12-06 |
| JP2017513913A (ja) | 2017-06-01 |
| IL248586A0 (en) | 2016-12-29 |
| BR112016024523A2 (pt) | 2017-08-15 |
| RU2016146097A3 (cg-RX-API-DMAC7.html) | 2018-11-15 |
| US20160024070A1 (en) | 2016-01-28 |
| EP3137461A1 (en) | 2017-03-08 |
| CA2946754A1 (en) | 2015-11-05 |
| EP3137461A4 (en) | 2017-09-13 |
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