CA2681650C - The use of pde7 inhibitors for the treatment of movement disorders - Google Patents
The use of pde7 inhibitors for the treatment of movement disorders Download PDFInfo
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- CA2681650C CA2681650C CA2681650A CA2681650A CA2681650C CA 2681650 C CA2681650 C CA 2681650C CA 2681650 A CA2681650 A CA 2681650A CA 2681650 A CA2681650 A CA 2681650A CA 2681650 C CA2681650 C CA 2681650C
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- pde7
- inhibiting
- alkyl
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Investigating Or Analysing Biological Materials (AREA)
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| US8637528B2 (en) | 2007-03-27 | 2014-01-28 | Omeros Corporation | Use of PDE7 inhibitors for the treatment of movement disorders |
| WO2010111060A1 (en) * | 2009-03-23 | 2010-09-30 | Merck Sharp & Dohme Corp. | P2x3, receptor antagonists for treatment of pain |
| FR2943673B1 (fr) * | 2009-03-27 | 2013-03-29 | Sanofi Aventis | Applications therapeutiques de derives de quinazolinedione |
| FR2944282B1 (fr) | 2009-04-09 | 2013-05-03 | Sanofi Aventis | Derives de quinazolinedione, leur preparation et leurs diverses applications therapeutiques |
| FR2944206B1 (fr) | 2009-04-09 | 2012-12-28 | Sanofi Aventis | Applications therapeutiques dans le domaine cardiovasculaire de derives de quinazolinedione |
| AU2013202493B2 (en) * | 2009-05-04 | 2016-03-10 | Omeros Corporation | Use of PDE7 inhibitors for the treatment of movement disorders |
| ES2353093B1 (es) | 2009-05-20 | 2012-01-03 | Consejo Superior De Investigaciones Científicas (Csic) | Uso de derivados de quinazolinas y sus composiciones farmacéuticas en enfermedades neurodegenerativas. |
| ES2360783B1 (es) | 2009-10-02 | 2012-07-04 | Consejo Superior De Investigaciones Científicas (Csic) | 1,2,4-tiadiazoles-5-imino sustituidos utiles en el tratamiento de enfermedades neurodegenerativas |
| US9220715B2 (en) | 2010-11-08 | 2015-12-29 | Omeros Corporation | Treatment of addiction and impulse-control disorders using PDE7 inhibitors |
| MX2013004943A (es) | 2010-11-08 | 2013-09-02 | Omeros Corp | Tratamiento de trastornos de adicion y control de impulsos usando inhibidores de pde7. |
| HRP20190279T1 (hr) * | 2012-05-07 | 2019-04-05 | Omeros Corporation | Liječenje ovisnosti i poremećaja nagona pomoću pde7 inhibitora |
| EP2846805B1 (en) * | 2012-05-07 | 2018-11-21 | Omeros Corporation | Treatment of addiction and impulse-control disorders using pde7 inhibitors |
| US20190185479A1 (en) * | 2016-08-26 | 2019-06-20 | Mitsubishi Tanabe Pharma Corporation | Bicyclic nitrogenated heterocyclic compound |
| JP2021535180A (ja) * | 2018-09-05 | 2021-12-16 | ユニベルシテイト ファン アムステルダム | パーキンソン病の処置の為のpde11又はpde2阻害剤の使用 |
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| WO2024259383A2 (en) * | 2023-06-14 | 2024-12-19 | President And Fellows Of Harvard College | Ion channel binders and uses thereof |
Family Cites Families (68)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5453566A (en) | 1986-03-28 | 1995-09-26 | Calgene, Inc. | Antisense regulation of gene expression in plant/cells |
| US4987071A (en) | 1986-12-03 | 1991-01-22 | University Patents, Inc. | RNA ribozyme polymerases, dephosphorylases, restriction endoribonucleases and methods |
| DE3852539T3 (de) | 1987-12-15 | 2005-08-04 | Gene Shears Pty. Ltd. | Ribozyme. |
| GB8822492D0 (en) | 1988-09-24 | 1988-10-26 | Considine J | Apparatus for removing tumours from hollow organs of body |
| US5789573A (en) | 1990-08-14 | 1998-08-04 | Isis Pharmaceuticals, Inc. | Antisense inhibition of ICAM-1, E-selectin, and CMV IE1/IE2 |
| IL108367A0 (en) | 1993-01-27 | 1994-04-12 | Hektoen Inst For Medical Resea | Antisense polynzcleotide inhibition of human growth factor-sensitive cancer cells |
| US5801154A (en) | 1993-10-18 | 1998-09-01 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of multidrug resistance-associated protein |
| US5739119A (en) | 1996-11-15 | 1998-04-14 | Galli; Rachel L. | Antisense oligonucleotides specific for the muscarinic type 2 acetylcholine receptor MRNA |
| US5932465A (en) * | 1997-10-16 | 1999-08-03 | Icos Corporation | Phosphodiesterase 8A |
| WO1999042596A2 (en) * | 1998-02-23 | 1999-08-26 | Icos Corporation | Phosphodiesterase 10 |
| DK1018559T3 (da) * | 1998-12-23 | 2007-12-03 | Pfizer | Phosphodiesteraser |
| AU4589800A (en) | 1999-05-05 | 2000-11-21 | Darwin Discovery Limited | 9-(1,2,3,4-tetrahydronaphthalen-1-yl)-1,9-dihydropurin-6-one derivatives as pde7inhibitors |
| WO2000068203A1 (en) | 1999-05-07 | 2000-11-16 | Takeda Chemical Industries, Ltd. | Cyclic compounds and uses thereof |
| US6146876A (en) | 1999-06-11 | 2000-11-14 | Millennium Pharmaceuticals, Inc. | 22025, a novel human cyclic nucleotide phosphodiesterase |
| DE19950647A1 (de) | 1999-10-21 | 2001-04-26 | Merck Patent Gmbh | Imidazolderivate als Phosphodiesterase VII-Hemmer |
| US7491742B2 (en) * | 1999-10-21 | 2009-02-17 | Merck Patent Gmbh | Imidazole derivatives as phosphodiesterase VII inhibitors |
| DE19953025A1 (de) | 1999-11-04 | 2001-05-10 | Merck Patent Gmbh | Pyrrolderivate als Phosphodiesterase VII-Hemmer |
| DE19953024A1 (de) * | 1999-11-04 | 2001-05-10 | Merck Patent Gmbh | Isoxazolderivate als Phosphodiesterase VII-Hemmer |
| DE19953414A1 (de) * | 1999-11-06 | 2001-05-10 | Merck Patent Gmbh | Imidazopyridinderivate als Phospodiesterase VII-Hemmer |
| DE19954707A1 (de) * | 1999-11-13 | 2001-05-17 | Merck Patent Gmbh | Imidazolverbindungen als Phosphodiesterase VII-Hemmer |
| US6649592B1 (en) | 2000-01-14 | 2003-11-18 | Science & Technology Corporation @ Unm | Peptide inhibitors of LFA-1/ICAM-1 interaction |
| KR20020097182A (ko) * | 2000-02-22 | 2002-12-31 | 셀러지 캐나다 인크. | 수면을 개선시키는 방법 및 조성물 |
| AU4415501A (en) | 2000-02-24 | 2001-09-03 | Bayer Aktiengesellschaft | Regulation of human gelatinase b-like enzyme 1 |
| GB0007934D0 (en) | 2000-03-31 | 2000-05-17 | Darwin Discovery Ltd | Chemical compounds |
| US7345031B2 (en) * | 2000-04-12 | 2008-03-18 | International Medical Innovations, Inc. | Pharmaceutical dopamine glycoconjugate compositions and methods of their preparation and use |
| GB0015095D0 (en) | 2000-06-20 | 2000-08-09 | Celltech Chiroscience Ltd | Chemical compounds |
| MXPA03001717A (es) | 2000-08-30 | 2003-09-22 | Lilly Icos Llc | METODO PARA EL TRATAMIENTO DE LA MIGRAnA. |
| EP1193261A1 (en) | 2000-10-02 | 2002-04-03 | Warner-Lambert Company | New thiadiazoles and their use as phosphodiesterase-7 inhibitors |
| WO2002040449A1 (en) | 2000-11-14 | 2002-05-23 | Altana Pharma Ag | Dihydroisoquinolines as novel phosphodiesterase inhibitors |
| CZ20031334A3 (cs) | 2000-11-14 | 2003-09-17 | Altana Pharma Ag | Isochinolinové deriváty a jejich použití jako inhibitory |
| IL140844A0 (en) * | 2001-01-10 | 2002-02-10 | Polygene Ltd | Cationic polysaccharide compositions |
| HUP0600103A2 (en) * | 2001-03-02 | 2006-06-28 | Bristol Myers Squibb Co | Co-administration of melanocortin receptor agonist and phosphodiesterase inhibitor for treatment of cyclic-amp associated disorders |
| US6617357B2 (en) * | 2001-03-06 | 2003-09-09 | Smithkline Beecham Corporation | Compounds and their use as PDE inhibitors |
| AP1699A (en) * | 2001-03-21 | 2006-12-26 | Warner Lambert Co | New spirotricyclic derivatives and their use as phosphodiesterase-7 inhibitors |
| US6903109B2 (en) * | 2001-04-18 | 2005-06-07 | Ortho-Muniel Pharmaceutical, Inc. | Arylindenopyridines and related therapeutic and prophylactic methods |
| JP2004532228A (ja) | 2001-04-18 | 2004-10-21 | オーソ−マクニール・フアーマシユーチカル・インコーポレーテツド | Pde阻害作用をもつアリールインデノピリジン |
| US6958328B2 (en) | 2001-04-18 | 2005-10-25 | Ortho-Mcneil Pharmaceutical, Inc | Arylindenopyridines and related therapeutic and prophylactic methods |
| US20030032579A1 (en) * | 2001-04-20 | 2003-02-13 | Pfizer Inc. | Therapeutic use of selective PDE10 inhibitors |
| PL363312A1 (en) | 2001-04-25 | 2004-11-15 | Altana Pharma Ag | Novel phthalazinones |
| US20030053980A1 (en) | 2001-04-30 | 2003-03-20 | The Gillette Company | Shaving compositions containing highly lubricious water soluble polymers |
| US6849638B2 (en) * | 2001-04-30 | 2005-02-01 | Bayer Pharmaceuticals Corporation | 4-amino-5,6-substituted thiopheno [2,3-d] pyrimidines, pharmaceutical compositions containing the same, and their use in the treatment or prevention of pde7b-mediated diseases and conditions |
| WO2002088079A2 (en) | 2001-05-01 | 2002-11-07 | Bristol-Myers Squibb Company | Dual inhibitors of pde 7 and pde 4 |
| BR0210030A (pt) * | 2001-06-15 | 2004-08-10 | Yamanouchi Pharma Co Ltd | Derivado de fenilpiridinacarbonilpiperazina |
| PE20030008A1 (es) * | 2001-06-19 | 2003-01-22 | Bristol Myers Squibb Co | Inhibidores duales de pde 7 y pde 4 |
| HUP0402352A2 (hu) * | 2001-06-19 | 2005-02-28 | Bristol-Myers Squibb Co. | Foszfodiészteráz (PDE) 7 inhibitorként alkalmazható pirimidinszármazékok és ezeket tartalmazó gyógyszerkészítmények |
| DE10130167A1 (de) * | 2001-06-22 | 2003-01-02 | Bayer Ag | Imidazotriazine |
| KR20040066788A (ko) * | 2001-08-31 | 2004-07-27 | 더 락커펠러 유니버시티 | 프스포다이에스터레이즈 활성 및 뇌에서프스포다이에스터레이즈 1b 매개되는 신호의 조절 |
| US20060286622A1 (en) * | 2001-09-28 | 2006-12-21 | Patricia Soulard | Polypeptides exhibiting PDE7 activity and their use for selecting compounds which inhibit PDE 7 enzyme activity |
| CA2439784C (en) * | 2001-12-13 | 2010-11-02 | Daiichi Suntory Pharma Co., Ltd. | Pyrazolopyrimidinone derivatives having pde7 inhibiting action |
| DE10163991A1 (de) * | 2001-12-24 | 2003-07-03 | Merck Patent Gmbh | Pyrrolo-pyrimidine |
| WO2003057149A2 (en) | 2001-12-28 | 2003-07-17 | Bayer Corporation | 4-substituted fused heteropyrimidines and fused hetero-4-pyrimidones |
| WO2003064389A1 (en) * | 2002-01-31 | 2003-08-07 | Ono Pharmaceutical Co., Ltd. | Nitrogen-containing bicyclic compounds and drugs containing the same as the active ingredient |
| US20040082061A1 (en) * | 2002-02-14 | 2004-04-29 | Anna Astromoff | Drug metabolizing enzymes |
| EP1348701A1 (en) | 2002-03-28 | 2003-10-01 | Warner-Lambert Company LLC | (2,4-disubstituted-thiazol-5-yl) amine compounds as PDE7 inhibitors |
| EP1348433A1 (en) | 2002-03-28 | 2003-10-01 | Warner-Lambert Company LLC | Thiazol-2-yl-imine compounds as PDE-7 inhibitors |
| EP1400244A1 (en) | 2002-09-17 | 2004-03-24 | Warner-Lambert Company LLC | New spirocondensed quinazolinones and their use as phosphodiesterase inhibitors |
| WO2004044196A1 (en) | 2002-11-13 | 2004-05-27 | Bayer Healthcare Ag | DIAGNOSTICS AND THERAPEUTICS FOR DISEASES ASSOCIATED WITH HUMAN PHOSPHODIESTERASE 7B (PDE7b) |
| ES2217956B1 (es) | 2003-01-23 | 2006-04-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de 4-aminotieno(2,3-d)pirimidin-6-carbonitrilo. |
| US7217527B2 (en) * | 2003-04-15 | 2007-05-15 | Vanderbilt University | Assay for phosphodiesterase function |
| JP2006219373A (ja) * | 2003-06-13 | 2006-08-24 | Daiichi Asubio Pharma Co Ltd | Pde7阻害作用を有するピリジニルピラゾロピリミジノン誘導体 |
| JP2006219374A (ja) | 2003-06-13 | 2006-08-24 | Daiichi Asubio Pharma Co Ltd | Pde7阻害作用を有するイミダゾトリアジノン誘導体 |
| WO2005018563A2 (en) * | 2003-08-22 | 2005-03-03 | Pharmacia Corporation | Compositions of a cyclooxygenase-2 selective inhibitor and a phosphodiesterase inhibitor for the treatment of ischemic mediated central nervous system disorders or injury |
| PT1775298E (pt) | 2004-07-01 | 2013-06-12 | Daiichi Sankyo Co Ltd | Derivado de tienopirazol com atividade inibidora da pde 7 |
| WO2006092692A1 (en) | 2005-03-01 | 2006-09-08 | Pfizer Limited | Use of combinations of pde7 inhibitors and alpha-2-delty ligands for the treatment of neuropathic pain |
| WO2006092691A1 (en) | 2005-03-01 | 2006-09-08 | Pfizer Limited | Use of pde7 inhibitors for the treatment of neuropathic pain |
| WO2007047978A2 (en) * | 2005-10-21 | 2007-04-26 | Braincells, Inc. | Modulation of neurogenesis by pde inhibition |
| AU2006321349A1 (en) * | 2005-12-02 | 2007-06-07 | Pfizer Limited | Spirocyclic quinazoline derivatives as PDE7 inhibitors |
| US8637528B2 (en) * | 2007-03-27 | 2014-01-28 | Omeros Corporation | Use of PDE7 inhibitors for the treatment of movement disorders |
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| NZ580413A (en) | 2012-11-30 |
| RU2009138966A (ru) | 2011-05-10 |
| CN104758291B (zh) | 2020-03-03 |
| US20080260643A1 (en) | 2008-10-23 |
| MX2009010450A (es) | 2009-11-23 |
| RU2449790C2 (ru) | 2012-05-10 |
| ES2533206T3 (es) | 2015-04-08 |
| US20110091388A1 (en) | 2011-04-21 |
| WO2008119057A3 (en) | 2008-11-20 |
| JP5580192B2 (ja) | 2014-08-27 |
| AU2008230710A1 (en) | 2008-10-02 |
| AU2008230710B2 (en) | 2014-04-10 |
| CA2681650A1 (en) | 2008-10-02 |
| CN101917992A (zh) | 2010-12-15 |
| HK1139861A1 (en) | 2010-09-30 |
| JP2014198718A (ja) | 2014-10-23 |
| US20190183824A1 (en) | 2019-06-20 |
| EP2139475A2 (en) | 2010-01-06 |
| BRPI0809244A2 (pt) | 2014-09-23 |
| EP2139475A4 (en) | 2012-03-07 |
| CN104758291A (zh) | 2015-07-08 |
| JP5943964B2 (ja) | 2016-07-05 |
| JP2010522768A (ja) | 2010-07-08 |
| WO2008119057A2 (en) | 2008-10-02 |
| EP2139475B1 (en) | 2014-12-17 |
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