CA2915405A1 - Compositions and methods for treating metabolic disorders - Google Patents
Compositions and methods for treating metabolic disorders Download PDFInfo
- Publication number
- CA2915405A1 CA2915405A1 CA2915405A CA2915405A CA2915405A1 CA 2915405 A1 CA2915405 A1 CA 2915405A1 CA 2915405 A CA2915405 A CA 2915405A CA 2915405 A CA2915405 A CA 2915405A CA 2915405 A1 CA2915405 A1 CA 2915405A1
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- Prior art keywords
- key element
- metabolic disorder
- receptor agonist
- sumn
- antagonist
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Classifications
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
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- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
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- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
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- A61K31/00—Medicinal preparations containing organic active ingredients
- 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
- A61K31/42—Oxazoles
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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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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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
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- Public Health (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361834864P | 2013-06-13 | 2013-06-13 | |
| US61/834,864 | 2013-06-13 | ||
| PCT/US2014/042397 WO2014201411A1 (en) | 2013-06-13 | 2014-06-13 | Compositions and methods for treating metabolic disorders |
Publications (1)
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|---|---|
| CA2915405A1 true CA2915405A1 (en) | 2014-12-18 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2915405A Abandoned CA2915405A1 (en) | 2013-06-13 | 2014-06-13 | Compositions and methods for treating metabolic disorders |
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| Country | Link |
|---|---|
| US (3) | US20150011554A1 (enExample) |
| EP (2) | EP3311842A1 (enExample) |
| JP (1) | JP2016521755A (enExample) |
| CN (1) | CN105579575A (enExample) |
| AU (1) | AU2014277952A1 (enExample) |
| BR (1) | BR112015031249A2 (enExample) |
| CA (1) | CA2915405A1 (enExample) |
| MX (1) | MX2015017253A (enExample) |
| WO (1) | WO2014201411A1 (enExample) |
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| US9655865B2 (en) | 2002-07-29 | 2017-05-23 | Veroscience, Llc | Therapeutic treatment for metabolic syndrome, type 2 diabetes, obesity, or prediabetes |
| US8821915B2 (en) | 2002-08-09 | 2014-09-02 | Veroscience, Llc | Therapeutic process for the treatment of the metabolic syndrome and associated metabolic disorders |
| WO2008157845A1 (en) | 2007-06-21 | 2008-12-24 | Veroscience, Llc | Method of treating metabolic disorders and depression with dopamine receptor agonists |
| US8741918B2 (en) | 2007-06-21 | 2014-06-03 | Veroscience Llc | Parenteral formulations of dopamine agonists |
| US20100035886A1 (en) | 2007-06-21 | 2010-02-11 | Veroscience, Llc | Parenteral formulations of dopamine agonists |
| US9352025B2 (en) | 2009-06-05 | 2016-05-31 | Veroscience Llc | Combination of dopamine agonists plus first phase insulin secretagogues for the treatment of metabolic disorders |
| US8431155B1 (en) | 2012-04-30 | 2013-04-30 | Veroscience Llc | Bromocriptine formulations |
| WO2017184875A1 (en) | 2016-04-20 | 2017-10-26 | Veroscience Llc | Composition and method for treating metabolic disorders |
| DK3697418T3 (da) | 2017-10-18 | 2024-10-07 | Veroscience Llc | Forbedrede formuleringer af bromocriptin |
| US20200397751A1 (en) * | 2017-12-05 | 2020-12-24 | Peter Vanderklish | Modulation of AMPA/kainate Receptors for the Treatment of Hypoglycemia |
| US12343359B2 (en) | 2019-05-23 | 2025-07-01 | Dignity Health | Inhibitory interneuron treatment methods, uses and compositions for diabetes |
| US11607455B2 (en) | 2019-09-23 | 2023-03-21 | Veroscience Llc | Method for inducing tumor regression |
Family Cites Families (110)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3784703A (en) * | 1972-02-29 | 1974-01-08 | Merck & Co Inc | Method of treating hypertension |
| US5017566A (en) | 1987-12-30 | 1991-05-21 | University Of Florida | Redox systems for brain-targeted drug delivery |
| US4939174A (en) | 1988-02-26 | 1990-07-03 | Shashoua Victor E | Appetite suppression with dopamine-fatty acid conjugates |
| US5994392A (en) | 1988-02-26 | 1999-11-30 | Neuromedica, Inc. | Antipsychotic prodrugs comprising an antipsychotic agent coupled to an unsaturated fatty acid |
| US4933324A (en) | 1988-02-26 | 1990-06-12 | Shashoua Victor E | Fatty acid-neuroactive drug conjugate as a prodrug |
| US5344832A (en) * | 1990-01-10 | 1994-09-06 | The Board Of Supervisors Of Louisiana University And Agricultural And Mechanical College | Method for the long term reduction of body fat stores, insulin resistance, hyperinsulinemia and hyperglycemia in vertebrates |
| AU3419293A (en) * | 1991-12-23 | 1993-07-28 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College, The | A therapeutic process for the treatment of the pathologies of type II diabetes |
| US5472954A (en) | 1992-07-14 | 1995-12-05 | Cyclops H.F. | Cyclodextrin complexation |
| US5324718A (en) | 1992-07-14 | 1994-06-28 | Thorsteinn Loftsson | Cyclodextrin/drug complexation |
| DE69331761T2 (de) | 1992-07-24 | 2002-09-12 | The Regents Of The University Of California, Oakland | Arzneimittel, die den durch ampa rezeptoren vermittelten synaptischen respons erhöhen |
| US20020099050A1 (en) | 1993-07-23 | 2002-07-25 | Lynch Gary S. | Drugs that enhance synaptic responses mediated by AMPA receptors |
| US6274600B1 (en) | 1995-06-05 | 2001-08-14 | The Regents Of The University Of California | Heteroatom substituted benzoyl derivatives that enhance synaptic responses mediated by AMPA receptors |
| US5488049A (en) | 1993-12-10 | 1996-01-30 | Fidia - Georgetown Institute For The Neuro-Sciences | Method of treating learning and memory disorders using benzothiadiazide derivatives as nootropic agents |
| US5852008A (en) | 1995-01-24 | 1998-12-22 | The Regents Of The University Of California | Heteroatom substituted benzoyl derivatives that enhance synaptic response mediated by receptors |
| US5650409A (en) | 1995-06-02 | 1997-07-22 | Cortex Pharmaceuticals, Inc. | Benzoyl piperidines/pyrrolidines for enhancing synaptic response |
| US5773434A (en) | 1995-08-30 | 1998-06-30 | Gary A. Rogers | Facilitation of AMPA receptor-mediated synaptic transmission in brain as a treatment for schizophrenia |
| US5686423A (en) * | 1996-02-16 | 1997-11-11 | Department Of Health, The Executive Yuan, Republic Of China | Di-and tri-peptide mimetic compounds for Parkinson's disease |
| US5891871A (en) | 1996-03-21 | 1999-04-06 | Cocensys, Inc. | Substituted 2,3-benzodiazepin-4-ones and the use thereof |
| US5736543A (en) | 1996-04-03 | 1998-04-07 | The Regents Of The University Of California | Benzoxazines for enhancing synaptic response |
| AU4345297A (en) | 1996-09-17 | 1998-04-14 | Regents Of The University Of California, The | Benzothiadiazide derivatives and their use as allosteric up-modulators of the ampa receptor |
| WO1998011892A1 (en) | 1996-09-17 | 1998-03-26 | The Regents Of The University Of California | Positive ampa receptor modulation to enhance brain neurotrophic factor expression |
| AU5106498A (en) * | 1996-10-22 | 1998-05-15 | Ergo Research Corporation | Method for increasing blood insulin levels in mammals |
| GB9702194D0 (en) | 1997-02-04 | 1997-03-26 | Lilly Co Eli | Sulphonide derivatives |
| US6110935A (en) | 1997-02-13 | 2000-08-29 | The Regents Of The University Of California | Benzofurazan compounds for enhancing glutamatergic synaptic responses |
| US6329368B1 (en) | 1997-05-09 | 2001-12-11 | The Regents Of The University Of California | Endocrine modulation with positive modulators of AMPA type glutamate receptors |
| US20050245612A1 (en) * | 2004-05-03 | 2005-11-03 | Blass John P | Pharmaceutical compositions for metabolic insufficiencies |
| US5985871A (en) | 1997-12-24 | 1999-11-16 | Cortex Pharmaceuticals, Inc. | Benzoxazine compounds for enhancing synaptic response |
| CN1293665A (zh) | 1998-02-18 | 2001-05-02 | 神经研究公司 | 新化合物及其用作阳性ampa受体调节剂 |
| US6943159B1 (en) | 1998-02-18 | 2005-09-13 | Neurosearch A/S | Compounds and their use as positive AMPA receptor modulators |
| JP2002504502A (ja) | 1998-02-24 | 2002-02-12 | イーライ・リリー・アンド・カンパニー | スルホンアミド誘導体 |
| US6174922B1 (en) | 1998-05-11 | 2001-01-16 | Eli Lilly And Company | Sulphonamide derivatives |
| EP1066039A4 (en) | 1998-03-02 | 2003-02-26 | Cocensys Inc | SUBSTITUTED QUINAZOLINE AND THEIR ANALOGS AND USES |
| US6107489A (en) | 1998-03-17 | 2000-08-22 | Conjuchem, Inc. | Extended lifetimes in vivo renin inhibitors |
| US6124278A (en) | 1998-04-03 | 2000-09-26 | The Regents Of The University Of California | Acylbenzoxazines for enhancing synaptic response |
| WO1999057119A1 (en) * | 1998-05-04 | 1999-11-11 | Neotherapeutics, Inc. | Novel dopamine-like 9-substituted hypoxanthine and methods of use |
| WO2000006083A2 (en) | 1998-07-31 | 2000-02-10 | Eli Lilly And Company | Sulfonamide derivatives |
| PE20000944A1 (es) | 1998-07-31 | 2000-09-20 | Lilly Co Eli | Derivados de sulfonamida |
| US6387954B1 (en) | 1998-07-31 | 2002-05-14 | Eli Lilly And Company | Alkenyl sulphonamide derivatives |
| PE20000942A1 (es) | 1998-07-31 | 2000-09-28 | Lilly Co Eli | Derivados de amida, carbamato y urea |
| CA2338930A1 (en) | 1998-07-31 | 2000-02-10 | Hamideh Zarrinmayeh | Heterocyclic sulphonamide derivatives |
| US6617351B1 (en) | 1998-07-31 | 2003-09-09 | Eli Lilly And Company | Amide, carbamate, and urea derivatives |
| WO2000006158A1 (en) | 1998-07-31 | 2000-02-10 | Eli Lilly And Company | Heterocyclyl sulphonamide derivatives |
| US6358981B1 (en) | 1998-07-31 | 2002-03-19 | Eli Lilly And Company | Sulphonamide derivatives |
| PE20000943A1 (es) | 1998-07-31 | 2000-09-28 | Lilly Co Eli | Derivados de sulfonamida |
| US6552086B1 (en) | 1998-07-31 | 2003-04-22 | Eli Lilly And Company | Sulfonamide derivatives |
| US6521605B1 (en) | 1998-07-31 | 2003-02-18 | Eli Lilly And Company | Amidophosphate derivatives |
| US6525099B1 (en) | 1998-07-31 | 2003-02-25 | Eli Lilly And Company | N-substituted sulfonamide derivatives |
| ATE374747T1 (de) | 1999-04-30 | 2007-10-15 | Lilly Co Eli | Monofluoralkylderivate |
| WO2000075123A1 (en) | 1999-06-04 | 2000-12-14 | Euro-Celtique S.A. | Substituted 5-oxo-5,6,7,8-tetrahydro-4h-1-benzopyrans and benzothiopyrans and the use thereof as potentiators of ampa |
| US6297226B1 (en) | 1999-10-15 | 2001-10-02 | Neotherapeutics, Inc. | Synthesis and methods of use of 9-substituted guanine derivatives |
| US6639107B1 (en) | 1999-12-08 | 2003-10-28 | Eli Lilly And Company | Cyclopentyl sulfonamide derivatives |
| EP1246797B1 (en) | 1999-12-08 | 2008-07-23 | Eli Lilly And Company | Cyclopentyl sulfonamide derivatives |
| DE10004572A1 (de) | 2000-02-02 | 2001-08-09 | Boehringer Ingelheim Pharma | Neue positive allosterische AMPA-Rezeptor Modulatoren (PAARM), Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel |
| US6911476B2 (en) | 2000-03-13 | 2005-06-28 | Eli Lilly And Company | Sulfonamide derivatives |
| US7345031B2 (en) * | 2000-04-12 | 2008-03-18 | International Medical Innovations, Inc. | Pharmaceutical dopamine glycoconjugate compositions and methods of their preparation and use |
| WO2001090056A1 (en) | 2000-05-19 | 2001-11-29 | Eli Lilly And Company | Sulfonamide derivatives |
| WO2001090057A1 (en) | 2000-05-19 | 2001-11-29 | Eli Lilly And Company | Sulfonamide derivatives |
| WO2001094306A2 (en) | 2000-06-06 | 2001-12-13 | Eli Lilly And Company | (bis)sulfonamide derivatives |
| CA2411811A1 (en) | 2000-06-13 | 2001-12-20 | Eli Lilly And Company | Sulfonamide derivatives |
| US20030225127A1 (en) | 2000-08-11 | 2003-12-04 | Bender David Michael | Heterocyclic sulfonamide derivatives |
| WO2002014275A2 (en) | 2000-08-11 | 2002-02-21 | Eli Lilly And Company | Heterocyclic sulfonamide derivatives and their use for potentiating glutamate receptor function |
| EP1315696A1 (en) | 2000-08-31 | 2003-06-04 | Eli Lilly And Company | Acetylenic sulfonamide derivatives |
| AU2002212959A1 (en) | 2000-10-13 | 2002-04-29 | Eli Lilly And Company | Cycloalkylfluorosulfonamide derivatives |
| WO2002049636A1 (en) * | 2000-12-19 | 2002-06-27 | Rajagopal Thiruvengadam | An antidiabetic composition of amino acids |
| AU2002307327A1 (en) * | 2001-05-04 | 2002-11-18 | Eli Lilly And Company | Use of an ampa receptor potentiator for the manufacture of a medicament for the treatment of type 2 diabetes |
| ITBO20010271A1 (it) | 2001-05-08 | 2002-11-08 | Giuseppe Cannazza | Metodo per il trattamento e la prevenzione dei disturbi del sistema nervoso centrale associati ad una alterazione della neurotrasmissione gl |
| US20030100552A1 (en) | 2001-05-17 | 2003-05-29 | Boehringer Ingelheim Pharma Kg | Positive allosteric AMPA receptor modulators (PAARM), processes for preparing them, and their use as pharmaceutical compositions |
| ATE298742T1 (de) | 2001-05-30 | 2005-07-15 | Lilly Co Eli | Zykloalkenylsulfonamidderivate |
| WO2002098846A1 (en) | 2001-06-05 | 2002-12-12 | Eli Lilly And Company | Sulfonamide derivatives |
| TWI232863B (en) | 2001-06-11 | 2005-05-21 | Akzo Nobel Nv | Benzoxazepine derivatives |
| WO2003011270A1 (de) * | 2001-07-31 | 2003-02-13 | Lothar Saiger | Mittel zur behandlung von depressionen enthaltend ein lokalanästhetikum |
| US7045543B2 (en) * | 2001-11-05 | 2006-05-16 | Enzrel Inc. | Covalent conjugates of biologically-active compounds with amino acids and amino acid derivatives for targeting to physiologically-protected sites |
| PL371722A1 (en) | 2001-11-26 | 2005-06-27 | Cortex Pharmaceuticals, Inc. | Carbonylbenzoxazine compounds for enhancing glutamatergic synaptic responses |
| AU2003254066B2 (en) * | 2002-07-19 | 2009-08-27 | The Regents Of The University Of California | Dendrimers as molecular translocators |
| US20050054652A1 (en) * | 2002-07-29 | 2005-03-10 | Cincotta Anthony H. | Methods of treating metabolic syndrome using dopamine receptor agonists |
| US9655865B2 (en) * | 2002-07-29 | 2017-05-23 | Veroscience, Llc | Therapeutic treatment for metabolic syndrome, type 2 diabetes, obesity, or prediabetes |
| US20080200453A1 (en) * | 2002-07-29 | 2008-08-21 | Cincotta Anthony H | Methods of treating metabolic syndrome using dopamine receptor agonists |
| FR2854634B1 (fr) | 2003-05-05 | 2005-07-08 | Servier Lab | Nouveaux derives de thiadiazine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| US7625932B2 (en) | 2003-10-08 | 2009-12-01 | Eli Lilly And Company | Pyrrole and pyrazole derivatives as potentiators of glutamate receptors |
| GB0407583D0 (en) * | 2004-04-05 | 2004-05-05 | Arbab Tarig S M | Diagnostic testing and related matters |
| WO2005110394A1 (ja) * | 2004-05-19 | 2005-11-24 | Ajinomoto Co., Inc. | 糖尿病治療薬 |
| BRPI0510776A (pt) | 2004-06-04 | 2007-11-20 | Xenoport Inc | pró-fármacos de levodopa, e suas composições e usos |
| NZ552979A (en) | 2004-08-09 | 2010-02-26 | Glaxo Group Ltd | Indane and tetralin derivatives which potentiate glutamate receptor and uses thereof in medicine |
| WO2006015827A1 (en) | 2004-08-09 | 2006-02-16 | Glaxo Group Limited | Compounds which potentiate glutamate receptor and uses thereof in medicine |
| GB0417709D0 (en) | 2004-08-09 | 2004-09-08 | Glaxo Group Ltd | Compounds |
| US20060167099A1 (en) * | 2004-11-09 | 2006-07-27 | Anat Biegon | Use of compositions that increase glutamate receptor activity in treatment of brain injury |
| EP1848695B1 (en) | 2005-02-15 | 2011-07-27 | Glaxo Group Limited | Compounds which potentiate glutamate receptor and uses thereof in medicine |
| US20060183803A1 (en) * | 2005-02-17 | 2006-08-17 | Instituto Del Metabolismo Celular, S.L. | L-aspartic acid for the treatment of assorted health problems |
| DE602006003661D1 (de) | 2005-06-06 | 2008-12-24 | Lilly Co Eli | Ampa-rezeptoren-verstärker |
| WO2006138243A2 (en) * | 2005-06-13 | 2006-12-28 | University Of Vermont And State Agricultural College | Inhibition of creatine uptake to promote weight loss |
| WO2007060144A2 (en) | 2005-11-22 | 2007-05-31 | Neurosearch A/S | Novel quinoxaline derivatives and their medical use |
| EP3132792B1 (en) * | 2005-11-22 | 2019-09-11 | Nalpropion Pharmaceuticals, Inc. | Composition and methods for increasing insulin sensitivity |
| EP1981865A1 (en) | 2006-02-08 | 2008-10-22 | Glaxo Group Limited | 4-phenyl-3-(2-propylsulfonylamino) tetrahydrofuran derivatives which potentiate glutamate receptors and are useful in the treatment of schizophrenia |
| GB0602560D0 (en) | 2006-02-08 | 2006-03-22 | Glaxo Group Ltd | Compounds |
| US7829592B2 (en) | 2006-12-21 | 2010-11-09 | Xenoport, Inc. | Catechol protected levodopa diester prodrugs, compositions, and methods of use |
| CA2673336A1 (en) | 2006-12-21 | 2008-06-26 | Xenoport, Inc. | Levodopa dimethyl-substituted diester prodrugs, compositions, and methods of use |
| GB0711088D0 (en) * | 2007-06-08 | 2007-07-18 | Glaxo Group Ltd | Compounds |
| US8741918B2 (en) * | 2007-06-21 | 2014-06-03 | Veroscience Llc | Parenteral formulations of dopamine agonists |
| GB0721094D0 (en) * | 2007-10-26 | 2007-12-05 | Glaxo Group Ltd | Compounds |
| GB0721092D0 (en) * | 2007-10-26 | 2007-12-05 | Glaxo Group Ltd | Compounds |
| US8466185B2 (en) * | 2008-03-12 | 2013-06-18 | Biocrine Ab | Methods and assays for detecting and treating hypoglycemia |
| WO2010015037A1 (en) * | 2008-08-08 | 2010-02-11 | Howard Florey Institute | Therapeutic methods and compositions |
| US8399513B2 (en) | 2008-10-20 | 2013-03-19 | Xenoport, Inc. | Levodopa prodrug mesylate hydrate |
| GB0821166D0 (en) * | 2008-11-19 | 2008-12-24 | Glaxo Group Ltd | Compounds |
| GB0822425D0 (en) * | 2008-12-09 | 2009-01-14 | Glaxo Group Ltd | Compounds |
| WO2010121023A2 (en) * | 2009-04-15 | 2010-10-21 | The Regents Of The University Of California | Peptides and aptamers for targeting of neuron or nerves |
| US10206921B2 (en) | 2009-06-03 | 2019-02-19 | The Regents Of The University Of California | Methods and compositions for treating a subject for central nervous system (CNS) injury |
| WO2011053869A2 (en) * | 2009-10-31 | 2011-05-05 | The Regents Of The University Of California | Manipulation of brain in a circuit-specific manner |
| EP2603513B1 (en) * | 2010-08-10 | 2020-03-11 | Takeda Pharmaceutical Company Limited | Heterocyclic compound and use thereof as ampa receptor positive allosteric modulator |
| US8697898B2 (en) | 2011-11-23 | 2014-04-15 | Instytut Medycyny Doswiadczalnej i Klinicznej im. M. Mossakowskiego PAN | Medical application of lipid derivatives of dopamine and the methods of their production |
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| MX2015017253A (es) | 2016-04-19 |
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| BR112015031249A2 (pt) | 2017-07-25 |
| US20150011554A1 (en) | 2015-01-08 |
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| EP3008167A4 (en) | 2017-06-07 |
| EP3008167A1 (en) | 2016-04-20 |
| US20190160059A1 (en) | 2019-05-30 |
| AU2014277952A1 (en) | 2016-01-28 |
| CN105579575A (zh) | 2016-05-11 |
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