BRPI0510022A - compostos de tienopiridinona e processos de tratamento - Google Patents
compostos de tienopiridinona e processos de tratamentoInfo
- Publication number
- BRPI0510022A BRPI0510022A BRPI0510022-4A BRPI0510022A BRPI0510022A BR PI0510022 A BRPI0510022 A BR PI0510022A BR PI0510022 A BRPI0510022 A BR PI0510022A BR PI0510022 A BRPI0510022 A BR PI0510022A
- Authority
- BR
- Brazil
- Prior art keywords
- disorders
- disease
- treatment
- compounds
- treatment processes
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title abstract 3
- 238000000034 method Methods 0.000 title abstract 2
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 abstract 2
- 206010047700 Vomiting Diseases 0.000 abstract 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 2
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 abstract 1
- 208000024827 Alzheimer disease Diseases 0.000 abstract 1
- 208000019901 Anxiety disease Diseases 0.000 abstract 1
- 206010003658 Atrial Fibrillation Diseases 0.000 abstract 1
- 206010010774 Constipation Diseases 0.000 abstract 1
- 208000030814 Eating disease Diseases 0.000 abstract 1
- 208000010228 Erectile Dysfunction Diseases 0.000 abstract 1
- 208000019454 Feeding and Eating disease Diseases 0.000 abstract 1
- 102000014630 G protein-coupled serotonin receptor activity proteins Human genes 0.000 abstract 1
- 208000007882 Gastritis Diseases 0.000 abstract 1
- 208000018522 Gastrointestinal disease Diseases 0.000 abstract 1
- 208000019695 Migraine disease Diseases 0.000 abstract 1
- 206010028813 Nausea Diseases 0.000 abstract 1
- 208000004756 Respiratory Insufficiency Diseases 0.000 abstract 1
- 206010038678 Respiratory depression Diseases 0.000 abstract 1
- 208000006011 Stroke Diseases 0.000 abstract 1
- 206010046543 Urinary incontinence Diseases 0.000 abstract 1
- 239000000556 agonist Substances 0.000 abstract 1
- 230000036506 anxiety Effects 0.000 abstract 1
- 206010003119 arrhythmia Diseases 0.000 abstract 1
- 230000006793 arrhythmia Effects 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 208000010877 cognitive disease Diseases 0.000 abstract 1
- 201000010099 disease Diseases 0.000 abstract 1
- 208000035475 disorder Diseases 0.000 abstract 1
- 235000014632 disordered eating Nutrition 0.000 abstract 1
- 201000006549 dyspepsia Diseases 0.000 abstract 1
- 230000030136 gastric emptying Effects 0.000 abstract 1
- 208000021302 gastroesophageal reflux disease Diseases 0.000 abstract 1
- 201000001881 impotence Diseases 0.000 abstract 1
- 208000002551 irritable bowel syndrome Diseases 0.000 abstract 1
- 208000023589 ischemic disease Diseases 0.000 abstract 1
- 230000001404 mediated effect Effects 0.000 abstract 1
- 206010027599 migraine Diseases 0.000 abstract 1
- 230000008693 nausea Effects 0.000 abstract 1
- 239000004031 partial agonist Substances 0.000 abstract 1
- 239000012450 pharmaceutical intermediate Substances 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 abstract 1
- 230000008673 vomiting Effects 0.000 abstract 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4743—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having sulfur as a ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/16—Central respiratory analeptics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Cardiology (AREA)
- Hospice & Palliative Care (AREA)
- Heart & Thoracic Surgery (AREA)
- Nutrition Science (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Pulmonology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Anesthesiology (AREA)
- Urology & Nephrology (AREA)
- Gynecology & Obstetrics (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Otolaryngology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
COMPOSTOS DE TIENOPIRIDINONA E PROCESSOS DE TRATAMENTO. A invenção refere-se a agonistas e a agonistas parciais do receptor de 5-HT. São divulgados novos compostos de tienopiridinona representados pela Fórmula 1 e a síntese e o uso dos mesmos para o tratamento doenças mediado diretamente ou indiretamente pelos receptores de 5-HT. Tais estados de saúde incluem doença de Alzheimer, distúrbios cognitivos, síndrome do intestino irritável, náusea, êmese, vómito, procinesia, doença de refluxo gastroesofageal, dispepsia sem ser úlcera, depressão, ansiedade, incontinência urinária, enxaqueca, arritmia, fibrilação atrial, derrame isquêmico, gastrite, distúrbios de esvaziamento gástrico, distúrbios alimentares, distúrbios gastrointestinais, constipação, disfunção erétil e depressão respiratória. Estão também incluídos processos de preparação e novos intermediários e sais farmacêuticos dos mesmos.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US57185204P | 2004-05-17 | 2004-05-17 | |
| US10/955,434 US7488736B2 (en) | 2004-05-17 | 2004-09-30 | Thienopyridinone compounds and methods of treatment |
| PCT/US2005/017121 WO2005121151A2 (en) | 2004-05-17 | 2005-05-16 | Thienopyridinone compounds and methods of treatment |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BRPI0510022A true BRPI0510022A (pt) | 2007-09-25 |
Family
ID=35310219
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BRPI0510022-4A BRPI0510022A (pt) | 2004-05-17 | 2005-05-16 | compostos de tienopiridinona e processos de tratamento |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US7488736B2 (pt) |
| EP (1) | EP1746994A4 (pt) |
| JP (1) | JP4897683B2 (pt) |
| KR (1) | KR101216296B1 (pt) |
| AU (1) | AU2005252632B2 (pt) |
| BR (1) | BRPI0510022A (pt) |
| CA (1) | CA2567268C (pt) |
| IL (1) | IL178996A0 (pt) |
| MA (1) | MA28582B1 (pt) |
| NO (1) | NO20065814L (pt) |
| RU (1) | RU2006144867A (pt) |
| WO (1) | WO2005121151A2 (pt) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050222175A1 (en) * | 2004-03-31 | 2005-10-06 | Dhanoa Dale S | New piperidinylamino-thieno[2,3-D] pyrimidine compounds |
| US7612078B2 (en) * | 2003-03-31 | 2009-11-03 | Epix Delaware, Inc. | Piperidinylamino-thieno[2,3-D] pyrimidine compounds |
| US7488736B2 (en) * | 2004-05-17 | 2009-02-10 | Epix Delaware, Inc. | Thienopyridinone compounds and methods of treatment |
| US7576211B2 (en) * | 2004-09-30 | 2009-08-18 | Epix Delaware, Inc. | Synthesis of thienopyridinone compounds and related intermediates |
| US7598265B2 (en) * | 2004-09-30 | 2009-10-06 | Epix Delaware, Inc. | Compositions and methods for treating CNS disorders |
| US7407966B2 (en) * | 2004-10-07 | 2008-08-05 | Epix Delaware, Inc. | Thienopyridinone compounds and methods of treatment |
| EP1856075A1 (en) * | 2005-01-25 | 2007-11-21 | Epix Delaware, Inc. | Substituted arylamine compounds and their use as 5-ht6 modulators |
| WO2007094937A1 (en) * | 2006-02-14 | 2007-08-23 | Exxonmobil Chemical Patents Inc. | A process for manufacturing mcm-22 family molecular sieves |
| EP2445877B1 (en) * | 2008-12-03 | 2014-07-23 | Nanotherapeutics, Inc. | Bicyclic compounds and methods of making and using same |
| US8557994B2 (en) * | 2009-07-27 | 2013-10-15 | Daljit Singh Dhanoa | Deuterium-enriched pyridinonecarboxamides and derivatives |
| US9453027B2 (en) | 2009-07-27 | 2016-09-27 | Daljit Singh Dhanoa | Deuterium-enriched pyridinonecarboxamides and derivatives |
| US8962598B2 (en) | 2010-10-14 | 2015-02-24 | Immunahr Ab | 1,2-dihydro-4-hydroxy-2-oxo-quinoline-3-carboxanilides as AHR activators |
| WO2013009827A1 (en) * | 2011-07-13 | 2013-01-17 | Tempero Pharmaceuticals, Inc. | Methods of treatment |
| WO2013009810A1 (en) * | 2011-07-13 | 2013-01-17 | Tempero Pharmaceuticals, Inc. | Methods of treatment |
| WO2013009830A1 (en) * | 2011-07-13 | 2013-01-17 | Tempero Pharmaceuticals, Inc. | Methods of treatment |
| WO2013009812A1 (en) * | 2011-07-13 | 2013-01-17 | Tempero Pharmaceuticals, Inc | Methods of treatment |
| GEP20247627B (en) | 2019-07-22 | 2024-05-27 | Lupin Ltd | Macrocyclic compounds as sting agonists and methods and uses thereof |
| CN114569566A (zh) * | 2020-12-02 | 2022-06-03 | 四川科瑞德制药股份有限公司 | 一种盐酸米那普仑制剂的制备方法 |
| DK4463457T3 (da) * | 2022-01-11 | 2026-03-02 | Suven Life Sciences Ltd | Pyrrolo[1,2-b]-2-pyridazinonforbindelser som 5-ht4-receptoragonister |
| US11725016B1 (en) * | 2022-06-02 | 2023-08-15 | Nanopharmaceutics, Inc | Compositions and methods for oral delivery of crystalline PRX-3140 potassium salt |
| WO2024253935A1 (en) * | 2023-06-05 | 2024-12-12 | Nanopharmaceutics, Inc. | Compositions and methods for oral delivery of sustained release crystalline prx-3140 |
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|---|---|---|---|---|
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| CA933923A (en) * | 1969-12-19 | 1973-09-18 | Eichenberger Kurt | Process for the manufacture of new thiopyranes |
| GB1570494A (en) * | 1975-11-28 | 1980-07-02 | Ici Ltd | Thienopyrimidine derivatives and their use as pesticides |
| DE2925175A1 (de) * | 1979-06-22 | 1981-01-08 | Basf Ag | Verfahren zur herstellung von isatosaeureanhydriden |
| IT1203323B (it) * | 1987-02-02 | 1989-02-15 | Hoechst Italia Spa | Additivo fotoattivatore per composizioni polimeriche costituito dal sale metallico di una cera ossidata |
| US5236917A (en) * | 1989-05-04 | 1993-08-17 | Sterling Winthrop Inc. | Saccharin derivatives useful as proteolytic enzyme inhibitors and compositions and method of use thereof |
| DE4008726A1 (de) | 1990-03-19 | 1991-09-26 | Basf Ag | Thieno(2,3-d)pyrimidinderivate |
| US5143919A (en) * | 1990-08-17 | 1992-09-01 | Takeda Chemical Industries, Ltd. | Thienopyridine derivatives and their pharmaceutical use |
| JP3086295B2 (ja) * | 1990-08-17 | 2000-09-11 | 武田薬品工業株式会社 | チエノピリジン誘導体、その製造法およびacat阻害剤 |
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-
2004
- 2004-09-30 US US10/955,434 patent/US7488736B2/en not_active Expired - Lifetime
-
2005
- 2005-05-16 EP EP05779361A patent/EP1746994A4/en not_active Withdrawn
- 2005-05-16 BR BRPI0510022-4A patent/BRPI0510022A/pt not_active Application Discontinuation
- 2005-05-16 WO PCT/US2005/017121 patent/WO2005121151A2/en not_active Ceased
- 2005-05-16 RU RU2006144867/04A patent/RU2006144867A/ru not_active Application Discontinuation
- 2005-05-16 CA CA2567268A patent/CA2567268C/en not_active Expired - Lifetime
- 2005-05-16 JP JP2007527345A patent/JP4897683B2/ja not_active Expired - Fee Related
- 2005-05-16 AU AU2005252632A patent/AU2005252632B2/en not_active Ceased
-
2006
- 2006-11-01 IL IL178996A patent/IL178996A0/en unknown
- 2006-11-13 MA MA29451A patent/MA28582B1/fr unknown
- 2006-11-15 KR KR1020067023904A patent/KR101216296B1/ko not_active Expired - Fee Related
- 2006-12-15 NO NO20065814A patent/NO20065814L/no not_active Application Discontinuation
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2008
- 2008-12-24 US US12/343,818 patent/US7982040B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| KR101216296B1 (ko) | 2012-12-28 |
| JP4897683B2 (ja) | 2012-03-14 |
| EP1746994A2 (en) | 2007-01-31 |
| US7982040B2 (en) | 2011-07-19 |
| AU2005252632A1 (en) | 2005-12-22 |
| EP1746994A4 (en) | 2008-01-23 |
| US7488736B2 (en) | 2009-02-10 |
| WO2005121151A3 (en) | 2006-05-18 |
| RU2006144867A (ru) | 2008-06-27 |
| US20050256153A1 (en) | 2005-11-17 |
| KR20070047237A (ko) | 2007-05-04 |
| IL178996A0 (en) | 2007-03-08 |
| MA28582B1 (fr) | 2007-05-02 |
| NO20065814L (no) | 2007-02-12 |
| CA2567268C (en) | 2013-07-09 |
| WO2005121151A2 (en) | 2005-12-22 |
| AU2005252632B2 (en) | 2012-03-01 |
| JP2007538084A (ja) | 2007-12-27 |
| CA2567268A1 (en) | 2005-12-22 |
| US20090163537A1 (en) | 2009-06-25 |
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