SK102698A3 - Diphenyl stilbenes as prodrugs to cox-2 inhibitors - Google Patents
Diphenyl stilbenes as prodrugs to cox-2 inhibitors Download PDFInfo
- Publication number
- SK102698A3 SK102698A3 SK1026-98A SK102698A SK102698A3 SK 102698 A3 SK102698 A3 SK 102698A3 SK 102698 A SK102698 A SK 102698A SK 102698 A3 SK102698 A3 SK 102698A3
- Authority
- SK
- Slovakia
- Prior art keywords
- diphenylstilbene
- group
- alkyl
- ome
- cox
- Prior art date
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- -1 Diphenyl stilbenes Chemical class 0.000 title description 18
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 title description 14
- 229940111134 coxibs Drugs 0.000 title description 13
- 239000000651 prodrug Substances 0.000 title description 8
- 229940002612 prodrug Drugs 0.000 title description 8
- 235000010290 biphenyl Nutrition 0.000 title 1
- 239000004305 biphenyl Substances 0.000 title 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 title 1
- 235000021286 stilbenes Nutrition 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 85
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- 201000010099 disease Diseases 0.000 claims abstract description 18
- 230000001404 mediated effect Effects 0.000 claims abstract description 15
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 49
- 125000000217 alkyl group Chemical group 0.000 claims description 29
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- DLNKOYKMWOXYQA-APPZFPTMSA-N phenylpropanolamine Chemical compound C[C@@H](N)[C@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-APPZFPTMSA-N 0.000 description 1
- 229960000395 phenylpropanolamine Drugs 0.000 description 1
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- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
- 208000026440 premature labor Diseases 0.000 description 1
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- 230000008569 process Effects 0.000 description 1
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- 229960000786 propylhexedrine Drugs 0.000 description 1
- JCRIVQIOJSSCQD-UHFFFAOYSA-N propylhexedrine Chemical compound CNC(C)CC1CCCCC1 JCRIVQIOJSSCQD-UHFFFAOYSA-N 0.000 description 1
- YIBNHAJFJUQSRA-YNNPMVKQSA-N prostaglandin H2 Chemical compound C1[C@@H]2OO[C@H]1[C@H](/C=C/[C@@H](O)CCCCC)[C@H]2C\C=C/CCCC(O)=O YIBNHAJFJUQSRA-YNNPMVKQSA-N 0.000 description 1
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- KWGRBVOPPLSCSI-WCBMZHEXSA-N pseudoephedrine Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WCBMZHEXSA-N 0.000 description 1
- 229960003908 pseudoephedrine Drugs 0.000 description 1
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- NMAOJFAMEOVURT-RTKIROINSA-N rosaprostol Chemical compound CCCCCC[C@H]1CCC(O)[C@@H]1CCCCCCC(O)=O NMAOJFAMEOVURT-RTKIROINSA-N 0.000 description 1
- 229950003055 rosaprostol Drugs 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- 238000013207 serial dilution Methods 0.000 description 1
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- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- PJANXHGTPQOBST-UHFFFAOYSA-N stilbene Chemical class C=1C=CC=CC=1C=CC1=CC=CC=C1 PJANXHGTPQOBST-UHFFFAOYSA-N 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical group CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000004114 suspension culture Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- LLPOLZWFYMWNKH-UHFFFAOYSA-N trans-dihydrocodeinone Natural products C1C(N(CCC234)C)C2CCC(=O)C3OC2=C4C1=CC=C2OC LLPOLZWFYMWNKH-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 1
- HMHSNGLUZWVXQY-UHFFFAOYSA-N trimethyl-(2-phenyl-1-trimethylsilyloxyethenoxy)silane Chemical compound C[Si](C)(C)OC(O[Si](C)(C)C)=CC1=CC=CC=C1 HMHSNGLUZWVXQY-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 201000010653 vesiculitis Diseases 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000012224 working solution Substances 0.000 description 1
- 229960000833 xylometazoline Drugs 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
-
- 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
- A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
- A61K31/10—Sulfides; Sulfoxides; Sulfones
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
- C07C311/29—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/16—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C317/22—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/24—Sulfones; Sulfoxides having sulfone or sulfoxide groups and doubly-bound oxygen atoms bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Rheumatology (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Polyesters Or Polycarbonates (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US1095096P | 1996-02-01 | 1996-02-01 | |
| GBGB9605647.8A GB9605647D0 (en) | 1996-03-18 | 1996-03-18 | Diphenyl stilbenes as prodrugs to cox-2 inhibitors |
| PCT/CA1997/000063 WO1997028120A1 (en) | 1996-02-01 | 1997-01-29 | Diphenyl stilbenes as prodrugs to cox-2 inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SK102698A3 true SK102698A3 (en) | 1999-04-13 |
Family
ID=26308949
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1026-98A SK102698A3 (en) | 1996-02-01 | 1997-01-29 | Diphenyl stilbenes as prodrugs to cox-2 inhibitors |
Country Status (19)
| Country | Link |
|---|---|
| EP (1) | EP0882015B1 (ko) |
| JP (1) | JP3662936B2 (ko) |
| KR (1) | KR19990082260A (ko) |
| CN (1) | CN1214677A (ko) |
| AT (1) | ATE198323T1 (ko) |
| AU (1) | AU707199B2 (ko) |
| CA (1) | CA2244134C (ko) |
| CZ (1) | CZ241698A3 (ko) |
| DE (1) | DE69703791T2 (ko) |
| EA (1) | EA199800675A1 (ko) |
| EE (1) | EE9800230A (ko) |
| ES (1) | ES2152648T3 (ko) |
| HU (1) | HUP9902119A3 (ko) |
| IL (1) | IL125441A0 (ko) |
| NO (1) | NO983511L (ko) |
| NZ (1) | NZ326283A (ko) |
| PL (1) | PL328225A1 (ko) |
| SK (1) | SK102698A3 (ko) |
| WO (1) | WO1997028120A1 (ko) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6635417B1 (en) | 1996-07-31 | 2003-10-21 | California Institute Of Technology | Complex formation between DSDNA and oligomer of cyclic heterocycles |
| US5998140A (en) * | 1996-07-31 | 1999-12-07 | The Scripps Research Institute | Complex formation between dsDNA and oligomer of cyclic heterocycles |
| JP2003523958A (ja) | 1999-12-23 | 2003-08-12 | ニトロメド インコーポレーテッド | ニトロソ化およびニトロシル化されたシクロオキシゲナーゼ−２の阻害剤、組成物ならびに使用法 |
| AR038957A1 (es) | 2001-08-15 | 2005-02-02 | Pharmacia Corp | Terapia de combinacion para el tratamiento del cancer |
| EP1527045A1 (en) * | 2002-07-26 | 2005-05-04 | Merck Frosst Canada & Co. | Nitric oxide releasing prodrugs of diaryl-2-(5h)-furanones as cyclooxygenase-2 inhibitors |
| US7244753B2 (en) | 2002-07-29 | 2007-07-17 | Nitromed, Inc. | Cyclooxygenase-2 selective inhibitors, compositions and methods of use |
| DE602004021238D1 (de) | 2003-03-05 | 2009-07-09 | Merck Frosst Company | Stickstoffmonoxid freisetzende prodrugs von diaryl-2-(5h)-furanonen als inhibitoren von cyclooxygenase-2 |
| WO2005070883A1 (en) * | 2004-01-27 | 2005-08-04 | Merck Frosst Company | Nitric oxide releasing prodrugs of diaryl-2-(5h)-furanones as cyclooxygenase-2 inhibitors |
| CN1914151A (zh) * | 2004-01-27 | 2007-02-14 | 默克弗罗斯特公司 | 作为环氧合酶－2抑制剂的二芳基－2(5h)－呋喃酮类的释放一氧化氮的前药 |
| WO2006029436A1 (de) * | 2004-09-17 | 2006-03-23 | Universität Wien | Cox-ii-inhibitorverbindungen |
| CA3209491A1 (en) | 2021-03-15 | 2022-09-22 | Saul Yedgar | Hyaluronic acid-conjugated dipalmitoyl phosphatidyl ethanolamine in combination with non-steroidal anti-inflammatory drugs (nsaids) for treating or alleviating inflammatory disease |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1990012786A1 (fr) * | 1989-04-24 | 1990-11-01 | Otsuka Pharmaceutical Factory, Inc. | Derive de 3-halogeno-2,3-diphenylacrylaldehyde, son procede de fabrication et agent de traitement de l'hyperlipidemie |
| US5474995A (en) * | 1993-06-24 | 1995-12-12 | Merck Frosst Canada, Inc. | Phenyl heterocycles as cox-2 inhibitors |
| US5393790A (en) * | 1994-02-10 | 1995-02-28 | G.D. Searle & Co. | Substituted spiro compounds for the treatment of inflammation |
-
1997
- 1997-01-29 PL PL97328225A patent/PL328225A1/xx unknown
- 1997-01-29 NZ NZ326283A patent/NZ326283A/xx unknown
- 1997-01-29 ES ES97900915T patent/ES2152648T3/es not_active Expired - Lifetime
- 1997-01-29 SK SK1026-98A patent/SK102698A3/sk unknown
- 1997-01-29 JP JP52720397A patent/JP3662936B2/ja not_active Expired - Fee Related
- 1997-01-29 EA EA199800675A patent/EA199800675A1/ru unknown
- 1997-01-29 EE EE9800230A patent/EE9800230A/xx unknown
- 1997-01-29 CA CA002244134A patent/CA2244134C/en not_active Expired - Fee Related
- 1997-01-29 KR KR1019980705989A patent/KR19990082260A/ko not_active Application Discontinuation
- 1997-01-29 HU HU9902119A patent/HUP9902119A3/hu unknown
- 1997-01-29 WO PCT/CA1997/000063 patent/WO1997028120A1/en not_active Application Discontinuation
- 1997-01-29 CN CN97193332A patent/CN1214677A/zh active Pending
- 1997-01-29 CZ CZ982416A patent/CZ241698A3/cs unknown
- 1997-01-29 IL IL12544197A patent/IL125441A0/xx unknown
- 1997-01-29 AU AU14346/97A patent/AU707199B2/en not_active Ceased
- 1997-01-29 EP EP97900915A patent/EP0882015B1/en not_active Expired - Lifetime
- 1997-01-29 AT AT97900915T patent/ATE198323T1/de not_active IP Right Cessation
- 1997-01-29 DE DE69703791T patent/DE69703791T2/de not_active Expired - Fee Related
-
1998
- 1998-07-30 NO NO983511A patent/NO983511L/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CA2244134C (en) | 2005-04-26 |
| NZ326283A (en) | 1998-12-23 |
| NO983511L (no) | 1998-09-30 |
| JP3662936B2 (ja) | 2005-06-22 |
| AU707199B2 (en) | 1999-07-08 |
| ATE198323T1 (de) | 2001-01-15 |
| KR19990082260A (ko) | 1999-11-25 |
| CZ241698A3 (cs) | 1998-12-16 |
| EP0882015B1 (en) | 2000-12-27 |
| DE69703791T2 (de) | 2001-06-21 |
| HUP9902119A3 (en) | 2001-08-28 |
| AU1434697A (en) | 1997-08-22 |
| NO983511D0 (no) | 1998-07-30 |
| PL328225A1 (en) | 1999-01-18 |
| MX9806213A (es) | 1998-12-31 |
| CA2244134A1 (en) | 1997-08-07 |
| ES2152648T3 (es) | 2001-02-01 |
| CN1214677A (zh) | 1999-04-21 |
| HUP9902119A2 (hu) | 2001-04-28 |
| DE69703791D1 (de) | 2001-02-01 |
| WO1997028120A1 (en) | 1997-08-07 |
| EE9800230A (et) | 1998-12-15 |
| IL125441A0 (en) | 1999-03-12 |
| EP0882015A1 (en) | 1998-12-09 |
| JP2000504332A (ja) | 2000-04-11 |
| EA199800675A1 (ru) | 1999-02-25 |
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