CN1280575A - 新型三环化合物和其作为药物的用途;其制备方法和包含该化合物的药物组合物 - Google Patents
新型三环化合物和其作为药物的用途;其制备方法和包含该化合物的药物组合物 Download PDFInfo
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- CN1280575A CN1280575A CN98811660A CN98811660A CN1280575A CN 1280575 A CN1280575 A CN 1280575A CN 98811660 A CN98811660 A CN 98811660A CN 98811660 A CN98811660 A CN 98811660A CN 1280575 A CN1280575 A CN 1280575A
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- ethoxy
- alkyl
- phenyl
- salts
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- 125000003118 aryl group Chemical group 0.000 claims description 114
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 114
- 125000000217 alkyl group Chemical group 0.000 claims description 108
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- 229910052739 hydrogen Inorganic materials 0.000 claims description 68
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- 125000005843 halogen group Chemical group 0.000 claims description 26
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- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 21
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- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 8
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- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 7
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- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
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- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 6
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- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 5
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- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 4
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- RMZRDGUAFKAILM-UHFFFAOYSA-N 2-ethoxy-2-methyl-3-[4-(2-phenothiazin-10-ylethoxy)phenyl]propanoic acid Chemical compound C1=CC(CC(C)(OCC)C(O)=O)=CC=C1OCCN1C2=CC=CC=C2SC2=CC=CC=C21 RMZRDGUAFKAILM-UHFFFAOYSA-N 0.000 claims 3
- HGVAYAMSAXHUEX-UHFFFAOYSA-N 2-ethoxy-2-methyl-3-[4-(2-phenoxazin-10-ylethoxy)phenyl]propanoic acid Chemical compound C1=CC(CC(C)(OCC)C(O)=O)=CC=C1OCCN1C2=CC=CC=C2OC2=CC=CC=C21 HGVAYAMSAXHUEX-UHFFFAOYSA-N 0.000 claims 3
- BGFOUGDAMJUJHB-UHFFFAOYSA-N 2-ethoxy-3-[2-(phenothiazin-10-ylmethyl)-1-benzofuran-5-yl]propanoic acid Chemical compound C12=CC=CC=C2SC2=CC=CC=C2N1CC1=CC2=CC(CC(OCC)C(O)=O)=CC=C2O1 BGFOUGDAMJUJHB-UHFFFAOYSA-N 0.000 claims 3
- QVOKAUNKFWROJV-UHFFFAOYSA-N 2-ethoxy-3-[4-(2-phenothiazin-10-ylethoxy)phenyl]propanoic acid Chemical compound C1=CC(CC(OCC)C(O)=O)=CC=C1OCCN1C2=CC=CC=C2SC2=CC=CC=C21 QVOKAUNKFWROJV-UHFFFAOYSA-N 0.000 claims 3
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- TXHKCGNKPCMEMF-UHFFFAOYSA-N 2-methyl-3-[4-(2-phenothiazin-10-ylethoxy)phenyl]-2-phenoxypropanoic acid Chemical compound C=1C=C(OCCN2C3=CC=CC=C3SC3=CC=CC=C32)C=CC=1CC(C)(C(O)=O)OC1=CC=CC=C1 TXHKCGNKPCMEMF-UHFFFAOYSA-N 0.000 claims 3
- OOSLNKYTDNHRSM-UHFFFAOYSA-N 3-[4-(2-phenothiazin-10-ylethoxy)phenyl]-2-phenoxypropanoic acid Chemical compound C=1C=C(OCCN2C3=CC=CC=C3SC3=CC=CC=C32)C=CC=1CC(C(=O)O)OC1=CC=CC=C1 OOSLNKYTDNHRSM-UHFFFAOYSA-N 0.000 claims 3
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- JMFKGSHXYLHZKB-UHFFFAOYSA-N methyl 2-ethoxy-3-[2-(phenothiazin-10-ylmethyl)-1-benzofuran-5-yl]propanoate Chemical compound C12=CC=CC=C2SC2=CC=CC=C2N1CC1=CC2=CC(CC(OCC)C(=O)OC)=CC=C2O1 JMFKGSHXYLHZKB-UHFFFAOYSA-N 0.000 claims 3
- LNNKQBVKNRBISO-UHFFFAOYSA-N methyl 2-ethoxy-3-[4-(2-phenothiazin-10-ylethoxy)phenyl]propanoate Chemical compound C1=CC(CC(OCC)C(=O)OC)=CC=C1OCCN1C2=CC=CC=C2SC2=CC=CC=C21 LNNKQBVKNRBISO-UHFFFAOYSA-N 0.000 claims 3
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- 229960004889 salicylic acid Drugs 0.000 description 1
- 231100000489 sensitizer Toxicity 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229960005137 succinic acid Drugs 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
Classifications
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- C07C59/40—Unsaturated compounds
- C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
- C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
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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
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- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/734—Ethers
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- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/34—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
- C07D265/38—[b, e]-condensed with two six-membered rings
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- C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
- C07D279/14—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems
- C07D279/18—[b, e]-condensed with two six-membered rings
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- C07D279/24—[b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom with hydrocarbon radicals, substituted by amino radicals, attached to the ring nitrogen atom
- C07D279/26—[b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom with hydrocarbon radicals, substituted by amino radicals, attached to the ring nitrogen atom without other substituents attached to the ring system
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- C07D417/06—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 carbon chain containing only aliphatic carbon atoms
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Abstract
Description
3,200MHz):δ1.12-1.29(复杂峰,6H),2.93(d,J=6.55Hz,2H),3.28-3.45(复杂峰,1H),3.51-3.68(复杂峰,1H),3.98(t,J=6.55Hz,1H),4.16(q,J=7.15Hz,2H),5.40(s,1H,D2O可交换),6.73(d,J=8.39Hz,2H),7.08(d,J=8.53Hz,2H)。
实施例号 | 浓度μM | PPARα | 浓度μM | PPARγ |
实施例11 | 50 | 6.42倍 | 1 | 5.20倍 |
实施例15 | 50 | 3.30倍 | 1 | 6.0倍 |
化合物 | 剂量(mg/kg) | 血葡萄糖含量的减少(%) | 甘油三酯的减少(%) |
实施例14 | 3 | 52 | 61 |
实施例11 | 10 | 66 | 50 |
Claims (40)
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IN2416CH1997 | 1997-10-27 | ||
PCT/US1998/001397 WO1999019313A1 (en) | 1997-10-27 | 1998-01-23 | Novel tricyclic compounds and their use in medicine; process for their preparation and pharmaceutical compositions containing them |
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CN1280575A true CN1280575A (zh) | 2001-01-17 |
CN100376560C CN100376560C (zh) | 2008-03-26 |
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EP (1) | EP1049684A1 (zh) |
KR (1) | KR100517644B1 (zh) |
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BR9508468A (pt) * | 1994-07-29 | 1997-11-25 | Smithkline Beecham Plc | Composto processo para a preparação do mesmo composição farmacéutica processos para o tratamento e/ou profilaxia de hiperglicemia em um mamifero humano ou não humano e para o tratamento de hiperlípidemia hipertensão doença cardiovascular alguns distúrbios de alimentação o tratamento e/ou profilaxia de doença renal a prevenção revers o estabilização ou retardo da progressão de microalbuminuria em um mamifero humano ou não humano uso do composto e composto intermediário |
US5622948A (en) * | 1994-12-01 | 1997-04-22 | Syntex (U.S.A.) Inc. | Pyrrole pyridazine and pyridazinone anti-inflammatory agents |
US5925656A (en) * | 1995-04-10 | 1999-07-20 | Dr. Reddy's Research Foundation | Compounds having antidiabetic, hypolipidemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them |
JPH0912575A (ja) * | 1995-06-28 | 1997-01-14 | Sankyo Co Ltd | ベンゾオキサジンおよびベンゾチアジン誘導体 |
GB9600464D0 (en) * | 1996-01-09 | 1996-03-13 | Smithkline Beecham Plc | Novel method |
WO1997037970A1 (fr) | 1996-04-04 | 1997-10-16 | Sankyo Company, Limited | Derives d'acide phenylalkylcarboxylique |
US5889032A (en) * | 1996-05-06 | 1999-03-30 | Dr. Reddy's Research Foundation | Heterocyclic compounds having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them |
US5919782A (en) * | 1996-05-06 | 1999-07-06 | Dr. Reddy's Research Foundation | Heterocyclic compounds having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them |
US5889025A (en) * | 1996-05-06 | 1999-03-30 | Reddy's Research Foundation | Antidiabetic compounds having hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them |
US5801173A (en) * | 1996-05-06 | 1998-09-01 | Dr. Reddy's Research Foundation | Heterocyclic compounds having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them |
CZ298812B6 (cs) * | 1996-07-01 | 2008-02-13 | Dr. Reddy's Laboratories Limited | Azolidindionové deriváty, způsob jejich přípravy, farmaceutické kompozice s jejich obsahem a jejich použití v léčbě diabetu a příbuzných nemocí |
US5885997A (en) * | 1996-07-01 | 1999-03-23 | Dr. Reddy's Research Foundation | Heterocyclic compounds, process for their preparation and pharmaceutical compositions containing them and their use in the treatment of diabetes and related diseases |
CN1190434C (zh) * | 1996-12-31 | 2005-02-23 | 雷迪实验室有限公司 | 新的杂环化合物、其制备方法和含有它们的药物组合物及其在治疗糖尿病和相关疾病中的应用 |
US6011036A (en) | 1997-04-15 | 2000-01-04 | Dr. Reddy's Research Foundation | Heterocyclic compounds having antidiabetic hypolipidemic antihypertensive properties process for their preparation and pharmaceutical compositions containing them |
US6011031A (en) | 1997-05-30 | 2000-01-04 | Dr. Reddy's Research Foundation | Azolidinediones useful for the treatment of diabetes, dyslipidemia and hypertension: process for their preparation and pharmaceutical compositions containing them |
EP0903343B1 (en) * | 1997-09-19 | 2003-05-28 | SSP Co., Ltd. | Alpha-Substituted phenylpropionic acid derivative and medicine containing the same |
HUP0003881A3 (en) | 1997-10-02 | 2001-04-28 | Sankyo Co | Amidocarboxylic acid derivatives |
US6440961B1 (en) | 1997-10-27 | 2002-08-27 | Dr. Reddy's Research Foundation | Tricyclic compounds and their use in medicine: process for their preparation and pharmaceutical compositions containing them |
CN100376560C (zh) | 1997-10-27 | 2008-03-26 | 雷迪实验室有限公司 | 新型三环化合物和其作为药物的用途;其制备方法和包含该化合物的药物组合物 |
US6265401B1 (en) | 1997-10-27 | 2001-07-24 | Reddy-Cheminor, Inc. | Bicyclic compounds and their use in medicine, process for their preparation and pharmaceutical compositions containing them |
AU763087B2 (en) | 1998-10-29 | 2003-07-10 | Dr. Reddy's Laboratories Limited | An improved process for the preparation of new antidiabetic agents |
WO2001040165A1 (en) | 1999-12-03 | 2001-06-07 | Astrazeneca Ab | Crystalline form of 3-{4-[2-(4-tert-butoxycarbonylaminophenyl)ethoxy]phenyl}-(s)-2-ethoxy propanoic acid |
SE9904413D0 (sv) | 1999-12-03 | 1999-12-03 | Astra Ab | Comminuted form |
ES2215769T3 (es) | 1999-12-03 | 2004-10-16 | Astrazeneca Ab | Forma cristalina de acido (s)-2-etoxi-3-(4-(2-(4-metanosulfoniloxifenil)etoxi)fenil)propanoico. |
SE9904421D0 (sv) | 1999-12-03 | 1999-12-03 | Astra Ab | New compounds |
SE9904412D0 (sv) | 1999-12-03 | 1999-12-03 | Astra Ab | Comminuted form |
SE9904415D0 (sv) | 1999-12-03 | 1999-12-03 | Astra Ab | New process |
TW574193B (en) | 1999-12-03 | 2004-02-01 | Astrazeneca Ab | Novel phenalkyloxy-phenyl derivatives, pharmaceutical composition containing the same and their uses |
CA2397828C (en) | 2000-01-19 | 2007-09-04 | Cadila Healthcare Ltd. | Compounds having hypolipidemic and hypocholesteremic activities, process for their preparation and pharmaceutical compositions containing them |
-
1998
- 1998-01-23 CN CNB98811660XA patent/CN100376560C/zh not_active Expired - Fee Related
- 1998-01-23 PL PL340549A patent/PL193086B1/pl unknown
- 1998-01-23 BR BR9812772-1A patent/BR9812772A/pt not_active Application Discontinuation
- 1998-01-23 RU RU2000114195/04A patent/RU2235094C2/ru not_active IP Right Cessation
- 1998-01-23 HU HU0100072A patent/HUP0100072A3/hu unknown
- 1998-01-23 AU AU60406/98A patent/AU749505B2/en not_active Ceased
- 1998-01-23 CA CA002307820A patent/CA2307820C/en not_active Expired - Fee Related
- 1998-01-23 GB GB0010176A patent/GB2364304B/en not_active Expired - Fee Related
- 1998-01-23 MX MXPA00004036A patent/MXPA00004036A/es not_active IP Right Cessation
- 1998-01-23 KR KR10-2000-7004478A patent/KR100517644B1/ko not_active IP Right Cessation
- 1998-01-23 US US09/012,585 patent/US6054453A/en not_active Expired - Fee Related
- 1998-01-23 EP EP98903706A patent/EP1049684A1/en not_active Withdrawn
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1999
- 1999-11-23 US US09/448,260 patent/US6939988B1/en not_active Expired - Fee Related
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2000
- 2000-04-26 NO NO20002113A patent/NO316515B1/no unknown
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2001
- 2001-12-06 US US10/007,109 patent/US20020077320A1/en not_active Abandoned
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2005
- 2005-07-14 US US11/182,032 patent/US7119198B2/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
AU749505B2 (en) | 2002-06-27 |
AU6040698A (en) | 1999-05-03 |
KR20010031446A (ko) | 2001-04-16 |
US6939988B1 (en) | 2005-09-06 |
RU2235094C2 (ru) | 2004-08-27 |
GB2364304A (en) | 2002-01-23 |
NO20002113L (no) | 2000-06-26 |
CN100376560C (zh) | 2008-03-26 |
GB2364304B (en) | 2003-04-23 |
HUP0100072A3 (en) | 2002-11-28 |
US6054453A (en) | 2000-04-25 |
US7119198B2 (en) | 2006-10-10 |
EP1049684A1 (en) | 2000-11-08 |
US20020077320A1 (en) | 2002-06-20 |
NO20002113D0 (no) | 2000-04-26 |
KR100517644B1 (ko) | 2005-09-28 |
PL193086B1 (pl) | 2007-01-31 |
HUP0100072A2 (hu) | 2001-08-28 |
CA2307820A1 (en) | 1999-04-22 |
PL340549A1 (en) | 2001-02-12 |
US20060148793A1 (en) | 2006-07-06 |
CA2307820C (en) | 2007-04-24 |
GB0010176D0 (en) | 2000-06-14 |
NO316515B1 (no) | 2004-02-02 |
BR9812772A (pt) | 2000-10-10 |
MXPA00004036A (es) | 2006-05-24 |
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