NO310496B1 - Anvendelse av isoksalin-forbindelser for fremstilling av et farmasöytisk preparat for å inhibere dannelse av TNF - Google Patents
Anvendelse av isoksalin-forbindelser for fremstilling av et farmasöytisk preparat for å inhibere dannelse av TNF Download PDFInfo
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- NO310496B1 NO310496B1 NO19963746A NO963746A NO310496B1 NO 310496 B1 NO310496 B1 NO 310496B1 NO 19963746 A NO19963746 A NO 19963746A NO 963746 A NO963746 A NO 963746A NO 310496 B1 NO310496 B1 NO 310496B1
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- hydrogen
- alkyl
- alkoxy
- phenyl ring
- compounds
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- 210000002437 synoviocyte Anatomy 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 description 1
- 239000002451 tumor necrosis factor inhibitor Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms 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
- A61K31/42—Oxazoles
-
- 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
- A61K31/42—Oxazoles
- A61K31/423—Oxazoles condensed with carbocyclic rings
-
- 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
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/04—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pulmonology (AREA)
- Diabetes (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Nutrition Science (AREA)
- Obesity (AREA)
- Transplantation (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Hydrogenated Pyridines (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US20912594A | 1994-03-09 | 1994-03-09 | |
PCT/IB1995/000078 WO1995024398A1 (en) | 1994-03-09 | 1995-02-03 | Isoxazoline compounds as inhibitors of tnf release |
Publications (3)
Publication Number | Publication Date |
---|---|
NO963746D0 NO963746D0 (no) | 1996-09-06 |
NO963746L NO963746L (no) | 1996-11-06 |
NO310496B1 true NO310496B1 (no) | 2001-07-16 |
Family
ID=22777444
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19963746A NO310496B1 (no) | 1994-03-09 | 1996-09-06 | Anvendelse av isoksalin-forbindelser for fremstilling av et farmasöytisk preparat for å inhibere dannelse av TNF |
Country Status (18)
Country | Link |
---|---|
US (2) | US5869511A (xx) |
EP (1) | EP0749428B1 (xx) |
JP (1) | JPH09505082A (xx) |
KR (1) | KR100200449B1 (xx) |
CN (1) | CN1143363A (xx) |
AT (1) | ATE169009T1 (xx) |
AU (1) | AU684887B2 (xx) |
CA (1) | CA2185019C (xx) |
DE (1) | DE69503769T2 (xx) |
DK (1) | DK0749428T3 (xx) |
ES (1) | ES2118557T3 (xx) |
FI (1) | FI963510A0 (xx) |
IL (1) | IL112847A (xx) |
MY (1) | MY114667A (xx) |
NO (1) | NO310496B1 (xx) |
NZ (1) | NZ278667A (xx) |
WO (1) | WO1995024398A1 (xx) |
ZA (1) | ZA951909B (xx) |
Families Citing this family (33)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6022977A (en) | 1997-03-26 | 2000-02-08 | Dupont Pharmaceuticals Company | Dynamic resolution of isoxazoline thioesters to isoxazoline carboxylic acids |
AU8977398A (en) * | 1997-07-23 | 1999-02-16 | Basf Aktiengesellschaft | Substituted 3-phenyl isoxazolines |
WO1999014210A1 (en) * | 1997-09-15 | 1999-03-25 | Warner-Lambert Company | Process for the preparation of substituted 5,6-dihydro-2h-pyran-2-ones |
EP1102755B1 (en) | 1998-08-07 | 2006-01-04 | Chiron Corporation | Substituted isoxazole derivatives as estrogen receptor modulators |
WO2000021959A1 (en) * | 1998-10-09 | 2000-04-20 | Janssen Pharmaceutica N.V. | 4,5-dihydro-isoxazole derivatives and their pharmaceutical use |
US20040220103A1 (en) | 1999-04-19 | 2004-11-04 | Immunex Corporation | Soluble tumor necrosis factor receptor treatment of medical disorders |
US20020077276A1 (en) * | 1999-04-27 | 2002-06-20 | Fredeking Terry M. | Compositions and methods for treating hemorrhagic virus infections and other disorders |
AU7322300A (en) * | 1999-09-17 | 2001-04-24 | Lg Chem Investment Ltd. | Caspase inhibitor |
KR100399361B1 (ko) * | 1999-11-04 | 2003-09-26 | 주식회사 엘지생명과학 | 캐스파제 억제제 함유 치료제 조성물 |
US6808902B1 (en) | 1999-11-12 | 2004-10-26 | Amgen Inc. | Process for correction of a disulfide misfold in IL-1Ra Fc fusion molecules |
GB0021776D0 (en) * | 2000-09-05 | 2000-10-18 | Arakis Ltd | The treatment of inflammatory disorders |
AU2002314944B2 (en) * | 2001-06-08 | 2008-03-06 | Cytokine Pharmasciences, Inc. | Isoxazoline compounds having MIF antagonist activity |
US6886964B2 (en) * | 2001-06-26 | 2005-05-03 | Allan Gardiner | Illuminator with filter array and bandwidth controller |
TR201809008T4 (tr) | 2001-06-26 | 2018-07-23 | Amgen Fremont Inc | Opgl ye karşi antikorlar. |
WO2004043349A2 (en) * | 2002-11-06 | 2004-05-27 | Bristol-Myers Squibb Company | Isoxazoline derivatives as inhibitors of matrix metalloproteinases and/or tnf-alpha converting enzyme |
PL378879A1 (pl) * | 2002-12-30 | 2006-05-29 | Amgen Inc. | Terapia skojarzona z czynnikami kostymulującymi |
CA2537185A1 (en) * | 2003-08-29 | 2005-03-10 | Ranbaxy Laboratories Limited | Inhibitors of phosphodiesterase type-iv |
EP1694655A2 (en) * | 2003-11-26 | 2006-08-30 | Ranbaxy Laboratories Limited | Phosphodiesterase inhibitors |
SI1731512T1 (sl) | 2004-03-05 | 2015-01-30 | Nissan Chemical Industries, Ltd. | Z izoksazolinom substituirana benzamidna spojina in sredstvo za uravnavanje škodljivih organizmov |
JP2007530598A (ja) * | 2004-03-26 | 2007-11-01 | サイトカイン・ファーマサイエンシズ・インコーポレーテッド | マクロファージ遊走阻害因子の阻害に関する、化合物、組成物、作製プロセス、および使用方法 |
RU2416606C2 (ru) | 2004-06-17 | 2011-04-20 | Инфинити Дискавери, Инк. | Соединения и способы для ингибирования взаимодействия bcl белков с компонентами по связыванию |
US7842815B2 (en) | 2004-06-17 | 2010-11-30 | Infinity Pharmaceuticals, Inc. | Compounds and methods for inhibiting the interaction of BCL proteins with binding partners |
US20080009535A1 (en) * | 2004-08-30 | 2008-01-10 | Sarala Balachandran | Inhibitors of phosphodiesterase type-IV |
US8304442B2 (en) * | 2005-03-15 | 2012-11-06 | Ganial Immunotherapeutics, Inc. | Compounds having immunomodulator activity |
ES2344027T3 (es) | 2006-03-10 | 2010-08-16 | Nissan Chemical Industries, Ltd. | Compuesto de isoxazolina sustituido y agente de control de plagas. |
US7932052B1 (en) * | 2006-07-24 | 2011-04-26 | The Regents Of The University Of Michigan | Use of methanobactin |
TWI389895B (zh) | 2006-08-21 | 2013-03-21 | Infinity Discovery Inc | 抑制bcl蛋白質與結合夥伴間之交互作用的化合物及方法 |
WO2008035316A2 (en) * | 2006-09-22 | 2008-03-27 | Ranbaxy Laboratories Limited | Phosphodiesterase inhibitors |
WO2008138516A1 (en) * | 2007-05-09 | 2008-11-20 | Ganial Immunoterapeutics Inc. | (s,r)-3-phenyl-4,5 dihydro-5-isoxazole acetic acid-nitric oxide and use thereof as anti-cancer and antiviral agent |
WO2010093588A1 (en) * | 2009-02-10 | 2010-08-19 | Celgene Corporation | Methods of using and compositions comprising pde4 modulators for treatment, prevention and management of tuberculosis |
ES2744245T3 (es) | 2012-04-17 | 2020-02-24 | Geneone Life Science Inc | Compuestos que tienen actividad inmunomoduladora |
CN102911131B (zh) * | 2012-10-24 | 2014-10-29 | 中化蓝天集团有限公司 | 一种双键桥三氟甲基异噁唑类化合物、其制备方法及应用 |
CN105814022B (zh) * | 2013-12-09 | 2018-09-28 | Ucb生物制药私人有限公司 | 作为tnf活性调节剂的稠合的二环杂芳族衍生物 |
Family Cites Families (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3995048A (en) * | 1975-10-20 | 1976-11-30 | Sandoz, Inc. | Isoxazolyl benzamides useful as tranquilizers and sleep-inducers |
US4112108A (en) * | 1976-12-06 | 1978-09-05 | Sandoz, Inc. | Isoxazolyl benzamides |
JPS5512038A (en) * | 1978-07-07 | 1980-01-28 | Ube Industries | Packing sack made of flat thread made from resin film |
JPS55104273A (en) * | 1979-02-05 | 1980-08-09 | Sankyo Co Ltd | 4-phenylisoxazole derivative and its preparation |
CA1128526A (en) * | 1979-10-05 | 1982-07-27 | Cdc Life Sciences Inc. | 3,4-diarylisoxazol-5-acetic acids |
WO1987006576A1 (en) * | 1986-04-29 | 1987-11-05 | Pfizer Inc. | Calcium independent camp phosphodiesterase inhibitor antidepressant |
US4892870A (en) * | 1988-08-01 | 1990-01-09 | Biofor, Ltd. | Oxaza heterocycles and pharmaceutical compositions containing same |
FR2639636B1 (fr) * | 1988-11-30 | 1994-03-04 | Novapharme | Nouveaux composes heterocycliques a activite anticonvulsivante, procede de preparation et compositions therapeutiques les contenant |
DE3914969A1 (de) * | 1989-05-02 | 1990-11-08 | Schering Ag | 5-substituierte 3-arylisoxazol-derivate, deren herstellung und verwendung als schaedlingsbekaempfungsmittel |
CA2017383A1 (en) * | 1989-06-08 | 1990-12-08 | Raymond R. Martodam | Use of vanilloids for the treatment of respiratory diseases or disorders |
KR920702621A (ko) * | 1989-06-13 | 1992-10-06 | 스튜어트 알. 슈터 | 단핵세포 및/또는 마크로파지에 의한 인터루킨-1 또는 종양회사인자 생성의 억제 |
WO1991007177A1 (en) * | 1989-11-13 | 1991-05-30 | Pfizer Inc. | Pyrimidone derivatives and analogs in the treatment of asthma or certain skin disorders |
GB9007762D0 (en) * | 1990-04-05 | 1990-06-06 | Beecham Group Plc | Novel compounds |
US5051438A (en) * | 1990-05-16 | 1991-09-24 | G. D. Searle & Co. | Alkoxy-substituted dihydrobenzopyran-2-carboxylic acids and derivatives thereof, compositions and use |
DE4016049A1 (de) * | 1990-05-18 | 1991-11-21 | Basf Ag | 3-isoxazolylbenzylester, ihre herstellung und ihre verwendung |
CA2095429A1 (en) * | 1990-11-06 | 1992-05-07 | Paul E. Bender | Imidazolidinone compounds |
PT100441A (pt) * | 1991-05-02 | 1993-09-30 | Smithkline Beecham Corp | Pirrolidinonas, seu processo de preparacao, composicoes farmaceuticas que as contem e uso |
JP2702833B2 (ja) * | 1991-10-09 | 1998-01-26 | 松下電器産業株式会社 | レーザ加工装置 |
EP0730588B1 (en) * | 1993-11-26 | 1997-07-02 | Pfizer Inc. | Isoxazoline compounds as antiinflammatory agents |
-
1995
- 1995-02-03 DE DE69503769T patent/DE69503769T2/de not_active Expired - Fee Related
- 1995-02-03 DK DK95906459T patent/DK0749428T3/da active
- 1995-02-03 KR KR1019960704949A patent/KR100200449B1/ko not_active IP Right Cessation
- 1995-02-03 US US08/700,431 patent/US5869511A/en not_active Expired - Fee Related
- 1995-02-03 NZ NZ278667A patent/NZ278667A/xx unknown
- 1995-02-03 AT AT95906459T patent/ATE169009T1/de not_active IP Right Cessation
- 1995-02-03 ES ES95906459T patent/ES2118557T3/es not_active Expired - Lifetime
- 1995-02-03 CN CN95192000A patent/CN1143363A/zh active Pending
- 1995-02-03 EP EP95906459A patent/EP0749428B1/en not_active Expired - Lifetime
- 1995-02-03 AU AU14647/95A patent/AU684887B2/en not_active Ceased
- 1995-02-03 WO PCT/IB1995/000078 patent/WO1995024398A1/en active IP Right Grant
- 1995-02-03 JP JP7523329A patent/JPH09505082A/ja active Pending
- 1995-02-03 CA CA002185019A patent/CA2185019C/en not_active Expired - Fee Related
- 1995-03-02 IL IL11284795A patent/IL112847A/xx not_active IP Right Cessation
- 1995-03-07 MY MYPI95000572A patent/MY114667A/en unknown
- 1995-03-08 ZA ZA951909A patent/ZA951909B/xx unknown
-
1996
- 1996-09-06 FI FI963510A patent/FI963510A0/fi not_active IP Right Cessation
- 1996-09-06 NO NO19963746A patent/NO310496B1/no not_active IP Right Cessation
-
1998
- 1998-11-06 US US09/187,833 patent/US6114367A/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
MX9603975A (es) | 1997-09-30 |
US5869511A (en) | 1999-02-09 |
NO963746D0 (no) | 1996-09-06 |
AU1464795A (en) | 1995-09-25 |
CA2185019C (en) | 2000-08-08 |
US6114367A (en) | 2000-09-05 |
AU684887B2 (en) | 1998-01-08 |
ES2118557T3 (es) | 1998-09-16 |
NZ278667A (en) | 2000-12-22 |
KR100200449B1 (ko) | 1999-06-15 |
CN1143363A (zh) | 1997-02-19 |
EP0749428B1 (en) | 1998-07-29 |
EP0749428A1 (en) | 1996-12-27 |
WO1995024398A1 (en) | 1995-09-14 |
DE69503769D1 (de) | 1998-09-03 |
ZA951909B (en) | 1996-09-09 |
ATE169009T1 (de) | 1998-08-15 |
JPH09505082A (ja) | 1997-05-20 |
DK0749428T3 (da) | 1998-11-16 |
IL112847A (en) | 1999-10-28 |
FI963510A (fi) | 1996-09-06 |
MY114667A (en) | 2002-12-31 |
DE69503769T2 (de) | 1998-12-03 |
FI963510A0 (fi) | 1996-09-06 |
NO963746L (no) | 1996-11-06 |
IL112847A0 (en) | 1995-06-29 |
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