AR011092A1 - A COMPOUND DERIVED FROM TIAZOL BENZENSULFONAMIDES AS BETA3 AGONISTS FOR THE TREATMENT OF DIABETES AND OBESITY, A PHARMACEUTICAL COMPOSITION THAT IT UNDERSTANDS AND THE USE OF THE SAME FOR THE MANUFACTURE OF A MEDICINAL PRODUCT. - Google Patents
A COMPOUND DERIVED FROM TIAZOL BENZENSULFONAMIDES AS BETA3 AGONISTS FOR THE TREATMENT OF DIABETES AND OBESITY, A PHARMACEUTICAL COMPOSITION THAT IT UNDERSTANDS AND THE USE OF THE SAME FOR THE MANUFACTURE OF A MEDICINAL PRODUCT.Info
- Publication number
- AR011092A1 AR011092A1 ARP980100357A ARP980100357A AR011092A1 AR 011092 A1 AR011092 A1 AR 011092A1 AR P980100357 A ARP980100357 A AR P980100357A AR P980100357 A ARP980100357 A AR P980100357A AR 011092 A1 AR011092 A1 AR 011092A1
- Authority
- AR
- Argentina
- Prior art keywords
- compounds
- treatment
- obesity
- diabetes
- sulfur
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D417/12—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 chain containing hetero atoms as chain links
-
- 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
- A61K31/41—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
- A61K31/425—Thiazoles
-
- 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
- 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
- A61P3/06—Antihyperlipidemics
-
- 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
- A61P3/08—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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D417/14—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 three or more hetero rings
Abstract
Las bencensulfonamidas tiazol-substituidas que comprende la formula I donde: X es (1) un enlace, (2) alquileno C1-C3, opcionalmente substituido con1 o 2 grupos seleccionados entre metilo y halogeno, (3) alquileno C1-C3, donde dicho alquileno contiene un oxígeno, opcionalemnte con 1 o 2 gruposseleccionados de metilo y halogeno; m es 0 a 5; A es (1) fenilo, (2)un anillo heterocíclico de 5 a 6 miembros con desde 1 a 4 heteroátomos seleccionado deoxígeno, azufre y nitrogeno, (3) un anillo benceno fusionado a un anillo carboxílico C5-C10, (4) un anillo heterocíclico de 5 a 6 miembros con desde 1a 4 heteroátomos seleccionado de oxigeno, azufre y nitrogeno o, (5) un anillo heterocíclico de 5 o 6 miembros con desde 1 a 4 heteroátomos seleccionado deoxigeno , azufre y nitrogeno fusionado a un anillo carboxílico C5-C10; R1 es (1) alquilo C1-C10 opcionalmente sustituido con hasta 5 grupos como se defineen la memoria descriptiva, son agonistas receptores beta3 adrenérgicos conmuy poca actividad receptora beta1 y beta2 adrenérgica y como tales los compuestosson capaces de aumentar la lipolisis y el gasto de energía en las células. Los compuestos tienen por lo tanto una potente actividad para el tratamiento deobesidad ydiabetes de tipo II. Los compuestos también pueden usarse para disminuir los niveles de triglicéridos y los niveles de colesterol o paraelevar los niveles de lipoproteína de alta densidad o para disminuir la motilidad intestinal. Ademáslos compuestos pueden usarse para reducirinflamacion neurogenica o como agentes antidepresivos. Los compuestos se preparan mediante acoplamiento substituido. se describen las composicionesfarmacéuticas y usos de dichos compuestos para la manufactura de un medicamento para usar en el tratamiento para usar en el tratamiento de diabetes y obesidadThe thiazole-substituted benzenesulfonamides comprising formula I where: X is (1) a bond, (2) C1-C3 alkylene, optionally substituted with 1 or 2 groups selected from methyl and halogen, (3) C1-C3 alkylene, where said alkylene contains an oxygen, optionally with 1 or 2 selected groups of methyl and halogen; m is 0 to 5; A is (1) phenyl, (2) a 5- to 6-membered heterocyclic ring with from 1 to 4 heteroatoms selected from oxygen, sulfur and nitrogen, (3) a benzene ring fused to a C5-C10 carboxylic ring, (4) a 5- to 6-membered heterocyclic ring with from 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen, or (5) a 5- or 6-membered heterocyclic ring with from 1 to 4 heteroatoms selected from deoxygen, sulfur, and nitrogen fused to a C5 carboxylic ring -C10; R1 is (1) C1-C10 alkyl optionally substituted with up to 5 groups as defined in the specification, they are beta3 adrenergic receptor agonists with little beta1 and beta2 adrenergic receptor activity and as such the compounds are capable of increasing lipolysis and energy expenditure in the cells. The compounds therefore have potent activity for the treatment of obesity and type II diabetes. The compounds can also be used to lower triglyceride levels and cholesterol levels or to raise high-density lipoprotein levels or to decrease intestinal motility. In addition, the compounds can be used to reduce neurogenic inflammation or as antidepressant agents. The compounds are prepared by substituted coupling. The pharmaceutical compositions and uses of said compounds for the manufacture of a medicament for use in treatment for use in the treatment of diabetes and obesity are described.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3676097P | 1997-01-28 | 1997-01-28 | |
| GBGB9705041.3A GB9705041D0 (en) | 1997-03-12 | 1997-03-12 | Thiazole benzenesulfonamides as selective B3 agonists for the treatment of diabetes and obesity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR011092A1 true AR011092A1 (en) | 2000-08-02 |
Family
ID=26311166
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP980100357A AR011092A1 (en) | 1997-01-28 | 1998-01-27 | A COMPOUND DERIVED FROM TIAZOL BENZENSULFONAMIDES AS BETA3 AGONISTS FOR THE TREATMENT OF DIABETES AND OBESITY, A PHARMACEUTICAL COMPOSITION THAT IT UNDERSTANDS AND THE USE OF THE SAME FOR THE MANUFACTURE OF A MEDICINAL PRODUCT. |
Country Status (22)
| Country | Link |
|---|---|
| EP (1) | EP0968209A1 (en) |
| JP (1) | JP2001509166A (en) |
| KR (1) | KR20000070568A (en) |
| CN (1) | CN1251099A (en) |
| AR (1) | AR011092A1 (en) |
| AU (1) | AU728812B2 (en) |
| BG (1) | BG103686A (en) |
| BR (1) | BR9807096A (en) |
| CA (1) | CA2278739A1 (en) |
| EA (1) | EA199900692A1 (en) |
| EE (1) | EE9900328A (en) |
| HR (1) | HRP980044A2 (en) |
| HU (1) | HUP0002053A3 (en) |
| ID (1) | ID22273A (en) |
| IL (1) | IL131130A0 (en) |
| IS (1) | IS5131A (en) |
| NO (1) | NO993646L (en) |
| PE (1) | PE52299A1 (en) |
| PL (1) | PL334833A1 (en) |
| SK (1) | SK100099A3 (en) |
| TR (1) | TR199902442T2 (en) |
| WO (1) | WO1998032753A1 (en) |
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| DE19824175A1 (en) * | 1998-05-29 | 1999-12-02 | Novartis Ag | Amino azole compounds |
| CN1977842A (en) | 2000-01-21 | 2007-06-13 | 诺瓦提斯公司 | Combinations comprising dipeptidylpeptidase-IV inhibitors and antidiabetic agents |
| EP1258253A1 (en) * | 2000-01-28 | 2002-11-20 | Asahi Kasei Kabushiki Kaisha | Novel remedies with the use of beta3 agonist |
| ES2217090T3 (en) | 2000-03-31 | 2004-11-01 | Pfizer Products Inc. | PROCEDURE FOR PREPARATION OF REPLACED PYRIDINS. |
| AU2001272917A1 (en) | 2000-07-13 | 2002-01-30 | Eli Lilly And Company | Beta3 adrenergic agonists |
| US6537994B2 (en) | 2000-07-17 | 2003-03-25 | Wyeth | Heterocyclic β3 adrenergic receptor agonists |
| US6465501B2 (en) | 2000-07-17 | 2002-10-15 | Wyeth | Azolidines as β3 adrenergic receptor agonists |
| US6498170B2 (en) * | 2000-07-17 | 2002-12-24 | Wyeth | Cyclamine sulfonamides as β-3 adrenergic receptor agonists |
| US6410734B1 (en) | 2000-07-17 | 2002-06-25 | Wyeth | 2-substituted thiazolidinones as beta-3 adrenergic receptor agonists |
| US6525202B2 (en) | 2000-07-17 | 2003-02-25 | Wyeth | Cyclic amine phenyl beta-3 adrenergic receptor agonists |
| US6369232B1 (en) * | 2000-08-15 | 2002-04-09 | Hoffmann-La Roche Inc. | Tetrazolyl-phenyl acetamide glucokinase activators |
| ATE329901T1 (en) | 2000-11-10 | 2006-07-15 | Lilly Co Eli | 3-SUBSTITUTED OXINDOL DERIVATIVES AS BETA-3 AGONISTS |
| AU2002221080A1 (en) * | 2000-12-08 | 2002-06-18 | Masami Kusaka | Substituted thiazole derivatives bearing 3-pyridyl groups, process for preparingthe same and use thereof |
| AR035605A1 (en) | 2000-12-11 | 2004-06-16 | Bayer Corp | DERIVATIVES OF AMINOMETIL CHROMANO DI-SUBSTITUTES, A METHOD FOR THEIR PREPARATION, PHARMACEUTICAL COMPOSITIONS AND THE USE OF SUCH DERIVATIVES FOR THE MANUFACTURE OF USEFUL MEDICINES AS BETA-3-ADRENE-RECEPTORS AGONISTS |
| AR035858A1 (en) | 2001-04-23 | 2004-07-21 | Bayer Corp | CHROME DERIVATIVES 2,6-SUBSTITUTES, PHARMACEUTICAL COMPOSITIONS, USE OF SUCH DERIVATIVES FOR THE MANUFACTURE OF USEFUL MEDICINES AS BETA-3 ADRENORRECEPTING AGONISTS |
| CA2450562A1 (en) * | 2001-06-22 | 2003-01-03 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| DE60211199T2 (en) | 2001-08-14 | 2007-02-01 | Eli Lilly And Co., Indianapolis | 3-SUBSTITUTED OXINDOL BETA-3 AGONISTS |
| ES2272749T3 (en) | 2001-08-14 | 2007-05-01 | Eli Lilly And Company | DERIVATIVES OF INDOL AS BETA-3 ADRENERGIC AGONISTS FOR THE TREATMENT OF TYPE 2 DIABETES. |
| US20050014805A1 (en) * | 2001-10-12 | 2005-01-20 | Chenzhi Zhang | Phenyl substituted 5-membered nitrogen containing heterocycles for the treatment of obesity |
| DE60204718T2 (en) | 2001-11-20 | 2006-05-18 | Eli Lilly And Co., Indianapolis | 3-SUBSTITUTED OXINDOL BETA 3 AGONISTS |
| AU2002353844A1 (en) | 2001-11-20 | 2003-06-10 | Eli Lilly And Company | Beta 3 adrenergic agonists |
| US7009060B2 (en) | 2002-01-11 | 2006-03-07 | Eli Lilly And Company | 2-oxo-benzimidazolyl substituted ethanolamine derivatives and their use as β3 agonists |
| US6872724B2 (en) | 2002-07-24 | 2005-03-29 | Merck & Co., Inc. | Polymorphs with tyrosine kinase activity |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| US20080125403A1 (en) | 2004-04-02 | 2008-05-29 | Merck & Co., Inc. | Method of Treating Men with Metabolic and Anthropometric Disorders |
| WO2006132196A1 (en) * | 2005-06-08 | 2006-12-14 | Asahi Kasei Pharma Corporation | NOVEL PHARMACEUTICAL COMPRISING β3 AGONIST |
| CA2622608C (en) | 2005-09-14 | 2014-08-19 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors for treating diabetes |
| EP1940842B1 (en) | 2005-09-29 | 2012-05-30 | Merck Sharp & Dohme Corp. | Acylated spiropiperidine derivatives as melanocortin-4 receptor modulators |
| CA2624440A1 (en) * | 2005-10-04 | 2007-04-19 | Merck & Co., Inc. | Combination therapy for the treatment of urinary frequency, urinary urgency and urinary incontinence |
| WO2008039327A2 (en) | 2006-09-22 | 2008-04-03 | Merck & Co., Inc. | Method of treatment using fatty acid synthesis inhibitors |
| US8106086B2 (en) | 2007-04-02 | 2012-01-31 | Msd K.K. | Indoledione derivative |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| WO2008151257A2 (en) | 2007-06-04 | 2008-12-11 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| WO2009149279A2 (en) | 2008-06-04 | 2009-12-10 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| WO2010009319A2 (en) | 2008-07-16 | 2010-01-21 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders |
| WO2010047982A1 (en) | 2008-10-22 | 2010-04-29 | Merck Sharp & Dohme Corp. | Novel cyclic benzimidazole derivatives useful anti-diabetic agents |
| WO2010051206A1 (en) | 2008-10-31 | 2010-05-06 | Merck Sharp & Dohme Corp. | Novel cyclic benzimidazole derivatives useful anti-diabetic agents |
| WO2011041293A1 (en) | 2009-09-30 | 2011-04-07 | Takeda Pharmaceutical Company Limited | Pyrazolo [1, 5-a] pyrimidine derivatives as apoptosis signal-regulating kinase 1 inhibitors |
| US8802695B2 (en) | 2010-02-03 | 2014-08-12 | Takeda Pharmaceutical Company Limited | Apoptosis signal-regulating kinase 1 inhibitors |
| AU2011218830B2 (en) | 2010-02-25 | 2014-07-24 | Merck Sharp & Dohme Corp. | Novel cyclic benzimidazole derivatives useful anti-diabetic agents |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| CN103476258B (en) | 2011-02-25 | 2017-04-26 | 默沙东公司 | Novel cyclic azabenzimidazole derivatives useful as anti-diabetic agents |
| EP2880028B1 (en) | 2012-08-02 | 2020-09-30 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| ES2394349B1 (en) | 2012-08-29 | 2013-11-04 | Fundación Centro Nacional De Investigaciones Cardiovasculares Carlos Iii | Use of selective beta-3 adrenergic receptor agonists for the treatment of pulmonary hypertension |
| US9784726B2 (en) | 2013-01-08 | 2017-10-10 | Atrogi Ab | Screening method, a kit, a method of treatment and a compound for use in a method of treatment |
| CA2898482A1 (en) | 2013-02-22 | 2014-08-28 | Linda L. Brockunier | Antidiabetic bicyclic compounds |
| EP2970119B1 (en) | 2013-03-14 | 2021-11-03 | Merck Sharp & Dohme Corp. | Novel indole derivatives useful as anti-diabetic agents |
| JP2016514671A (en) | 2013-03-15 | 2016-05-23 | シナジー ファーマシューティカルズ インコーポレイテッド | Guanylate cyclase agonists and uses thereof |
| EP2968439A2 (en) | 2013-03-15 | 2016-01-20 | Synergy Pharmaceuticals Inc. | Compositions useful for the treatment of gastrointestinal disorders |
| CA2913737A1 (en) | 2013-06-05 | 2014-12-11 | Synergy Pharmaceuticals, Inc. | Ultra-pure agonists of guanylate cyclase c, method of making and using same |
| WO2015051496A1 (en) | 2013-10-08 | 2015-04-16 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| EP3551176A4 (en) | 2016-12-06 | 2020-06-24 | Merck Sharp & Dohme Corp. | Antidiabetic heterocyclic compounds |
| EP3558298A4 (en) | 2016-12-20 | 2020-08-05 | Merck Sharp & Dohme Corp. | Antidiabetic spirochroman compounds |
| GB201714736D0 (en) | 2017-09-13 | 2017-10-25 | Atrogi Ab | New compounds and uses |
| GB201714734D0 (en) | 2017-09-13 | 2017-10-25 | Atrogi Ab | New compounds and uses |
| GB201714745D0 (en) | 2017-09-13 | 2017-10-25 | Atrogi Ab | New compounds and uses |
| GB201714740D0 (en) | 2017-09-13 | 2017-10-25 | Atrogi Ab | New compounds and uses |
| GB202205895D0 (en) | 2022-04-22 | 2022-06-08 | Atrogi Ab | New medical uses |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| EP0091749A3 (en) * | 1982-04-08 | 1984-12-05 | Beecham Group Plc | Ethanolamine derivatives, process for their preparation and pharmaceutical compositions containing them |
| US5451677A (en) * | 1993-02-09 | 1995-09-19 | Merck & Co., Inc. | Substituted phenyl sulfonamides as selective β 3 agonists for the treatment of diabetes and obesity |
| IL113410A (en) * | 1994-04-26 | 1999-11-30 | Merck & Co Inc | Substituted sulfonamides having an asymmetric center and pharmaceutical compositions containing them |
-
1998
- 1998-01-23 BR BR9807096-7A patent/BR9807096A/en not_active IP Right Cessation
- 1998-01-23 PL PL98334833A patent/PL334833A1/en unknown
- 1998-01-23 EE EEP199900328A patent/EE9900328A/en unknown
- 1998-01-23 ID IDW990755A patent/ID22273A/en unknown
- 1998-01-23 HU HU0002053A patent/HUP0002053A3/en unknown
- 1998-01-23 KR KR1019997006814A patent/KR20000070568A/en not_active Application Discontinuation
- 1998-01-23 SK SK1000-99A patent/SK100099A3/en unknown
- 1998-01-23 CN CN98803585A patent/CN1251099A/en active Pending
- 1998-01-23 IL IL13113098A patent/IL131130A0/en unknown
- 1998-01-23 AU AU60384/98A patent/AU728812B2/en not_active Ceased
- 1998-01-23 JP JP53214898A patent/JP2001509166A/en active Pending
- 1998-01-23 WO PCT/US1998/001317 patent/WO1998032753A1/en not_active Application Discontinuation
- 1998-01-23 CA CA002278739A patent/CA2278739A1/en not_active Abandoned
- 1998-01-23 EP EP98903677A patent/EP0968209A1/en not_active Withdrawn
- 1998-01-23 EA EA199900692A patent/EA199900692A1/en unknown
- 1998-01-23 TR TR1999/02442T patent/TR199902442T2/en unknown
- 1998-01-27 AR ARP980100357A patent/AR011092A1/en unknown
- 1998-01-28 PE PE1998000064A patent/PE52299A1/en not_active Application Discontinuation
- 1998-01-28 HR HR9705041.3A patent/HRP980044A2/en not_active Application Discontinuation
-
1999
- 1999-07-23 IS IS5131A patent/IS5131A/en unknown
- 1999-07-27 NO NO993646A patent/NO993646L/en not_active Application Discontinuation
- 1999-08-24 BG BG103686A patent/BG103686A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PL334833A1 (en) | 2000-03-27 |
| EP0968209A1 (en) | 2000-01-05 |
| EE9900328A (en) | 2000-02-15 |
| CA2278739A1 (en) | 1998-07-30 |
| JP2001509166A (en) | 2001-07-10 |
| AU6038498A (en) | 1998-08-18 |
| NO993646L (en) | 1999-09-27 |
| BG103686A (en) | 2000-06-30 |
| SK100099A3 (en) | 2000-05-16 |
| EA199900692A1 (en) | 2000-02-28 |
| IS5131A (en) | 1999-07-23 |
| CN1251099A (en) | 2000-04-19 |
| ID22273A (en) | 1999-09-23 |
| WO1998032753A1 (en) | 1998-07-30 |
| AU728812B2 (en) | 2001-01-18 |
| BR9807096A (en) | 2000-04-18 |
| PE52299A1 (en) | 1999-05-26 |
| IL131130A0 (en) | 2001-01-28 |
| HRP980044A2 (en) | 1998-10-31 |
| HUP0002053A3 (en) | 2001-09-28 |
| NO993646D0 (en) | 1999-07-27 |
| HUP0002053A2 (en) | 2001-08-28 |
| TR199902442T2 (en) | 2000-07-21 |
| KR20000070568A (en) | 2000-11-25 |
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