JP2001503403A - ビタミンd類似体 - Google Patents
ビタミンd類似体Info
- Publication number
- JP2001503403A JP2001503403A JP51993198A JP51993198A JP2001503403A JP 2001503403 A JP2001503403 A JP 2001503403A JP 51993198 A JP51993198 A JP 51993198A JP 51993198 A JP51993198 A JP 51993198A JP 2001503403 A JP2001503403 A JP 2001503403A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- mmol
- diseases
- ether
- production example
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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- 229940046008 vitamin d Drugs 0.000 title description 21
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- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 claims description 2
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- 238000006894 reductive elimination reaction Methods 0.000 claims 1
- 229910001023 sodium amalgam Inorganic materials 0.000 claims 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 4
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- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
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- 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
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- KPZSTOVTJYRDIO-UHFFFAOYSA-K trichlorocerium;heptahydrate Chemical compound O.O.O.O.O.O.O.Cl[Ce](Cl)Cl KPZSTOVTJYRDIO-UHFFFAOYSA-K 0.000 description 1
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Classifications
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- C07C401/00—Irradiation products of cholesterol or its derivatives; Vitamin D derivatives, 9,10-seco cyclopenta[a]phenanthrene or analogues obtained by chemical preparation without irradiation
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- A61P17/10—Anti-acne agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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- A—HUMAN NECESSITIES
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- 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
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- 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]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.式I: [式中、Xは水素またはヒドロキシであり;R1およびR2は同一または異なって 、水素またはC1−C5ヒドロカルビルであり、ヒドロカルビル(/ヒドロカルビ レン)は、直鎖、分枝または環状の飽和または不飽和炭化水素から1(/2)個 の水素原子を除去した後の基(二価の基)を意味し、あるいはR1およびR2は基 Xの結合した炭素原子と共にC3−C8炭素環を形成し得;Qはメチレン、エチレ ン、トリ−またはテトラ−メチレンであり、場合によりオキシ基−OR3で置換 されていることがあり、R3は水素、メチルまたはエチルであり;Yは一重結合 またはC1−C2ヒドロカルビレンであり;R1、R2および/またはY中の1個ま たはそれ以上の炭素は、場合により1個もしくはそれ以上のフッ素原子またはヒ ドロキシル基で置換されていることがある。] で示される化合物。 2.Xがヒドロキシであり、Yが一重結合である請求項1記載の化合物。 3.R1およびR2が同じ基で、いずれもメチルまたはエチルであるか、または 異なって水素およびシクロプロピルである請求項1または2記載の化合物I。 4.請求項1または2記載の化合物の純粋形態のジアステレオマー;またはそ のようなジアステレオマーの混合物であって、結晶形態そのもの、もしくは溶媒 和物、例えば水和物として、または非晶質形態で回収される化合物。 5.a)1(S),3(R),25−トリヒドロキシ−20(S)−9,10−セコ− コレスタ−5(Z),7(E),10(19),23(E)−テトラエン b)1(S),3(R)−ジヒドロキシ−20(S)−(6'−ヒドロキシ−6'−メチ ル−4'(E)−ヘプテン−1'−イル)−9,10−17コープレグナ−5(Z),7( E),10(19)−トリエン c)1(S),3(R),22(S),25−テトラヒドロキシ−20(R)−9,10− セコ−コレスタ−5(Z),7(E),10(19),23(E)−テトラエン d)22(S)−エトキシ−1(S),3(R),25−トリヒドロキシ−20(R)− 9,10−セコ−コレスタ−5(Z),7(E),10(19),23(E)−テトラエン e)1(S),3(R)−ジヒドロキシ−20(R)−(1'(R)−メトキシ−5'−ヒ ドロキシ−5'−エチル−3'(E)−ヘプテン−1'−イル)−9,10−セコ−プ レグナ−5(Z),7(E),10(19)−トリエン f)1(S),3(R)−ジヒドロキシ−20(S)−(4'−ヒドロキシ−4'−シク ロプロピル−2'(E)−ブテン−1'−イル)−9,10−セコ−プレグナ−5(Z) ,7(E),10(19)−トリエン である請求項1記載の化合物。 6.請求項1記載の化合物Iの製法であって、アルデヒド、すなわち1(S), 3(R)−ビス−(t−ブチルジメチルシリルオキシ)−20(S)−ホルミルメチル −9,10−セコ−プレグナ−5(E),7(E),10(19)−トリエンまたは1(S ),3(R)−ビス−(t−ブチルジメチルシリルオキシ)−20(S)−(2−ホルミ ルエチル)−9,10−セコ−プレグナ−5(E),7(E),10(19)−トリエンま たは1(S),3(R)−ビス−(t−ブチルジメチルシリルオキシ)−20(R)−(3 −ホルミルプロピル)−9,10−セコ−プレグナ−5(E),7(E),10(19)− トリエンあるいはC−20へのメチレン結合がメトキシ、エトキシまたはt−ブ チルジメチルシリルオキシ置換基を有する上記アルデヒドの1種に対応する誘導 体を、 カルボニル基を有するヴィッティッヒ試薬、例えばメチル(トリフェニ ルホスホラニリデン)アセテートと反応させ、得られた生成物を有機 リチウムもしくはグリニヤール試薬または還元剤と反応させるか、あ るいは、 場合によりヒドロキシル化したアルキルフェニルスルホンのリチオ誘 導体と反応させ、次いで還元的脱離(例えばナトリウムアマルガムに よる)する ことによって生成物を生成し、この生成物を、三重項増感剤(例えばアントラセ ン)の存在下の紫外線による異性化と、シリル基除去(例えばテトラブチルアン モニウムフロリドによる)とに、任意の順序で付すことを含んで成る方法。 7.請求項1〜5のいずれかに記載の化合物1種またはそれ以上の有効量を、 薬学的に許容し得る無毒性担体および/または助剤と共に含有する薬剤組成物。 8.化合物Iが用量単位の0.1ppmないし0.1重量%を占める用量単位形 態である請求項7記載の薬剤組成物。 9.異常な細胞分化および/または細胞増殖によって特徴付けられる疾患、例 えば乾癬および他の角化障害、HIV関与皮膚疾患、創傷、癌(皮膚癌を包含す る)、免疫系の疾患または平衡失調、例えば宿主対移植片および移植片対宿主反 応、および移植片拒絶、自己免疫疾患、例えば円瘡状および全身性の紅斑性狼癒 、真性糖尿病および自己免疫型慢性皮膚疾患(例えば強皮症および尋常性天疱瘡) 、炎症性疾患、例えばリューマチ様関節炎および喘息、多くの他の病態、例えば 上皮小体機能亢進症(特に、腎不全に伴う続発性の上皮小体機能亢進症)、認識障 害または老人性痴呆(アルツハイマー病)および他の神経変性疾患、高血圧症、ア クネ、脱毛症、皮膚萎縮(例えばステロイド誘発性皮膚萎縮)、皮膚老化(光老化 を包含する)を治療または予防し;骨形成を促進し;骨粗鬆症および骨軟化症を 治療/予防する方法であって、このような処置を要する患者に、請求項7記載の 薬剤組成物を有効量で投与することを含んで成る方法。 10.異常な細胞分化および/または細胞増殖によって特徴付けられる疾患、 例えば乾癬および他の角化障害、HIV関与皮膚疾患、創傷、癌(皮膚癌を包含 する)、免疫系の疾患または平衡失調、例えば宿主対移植片および移植片対宿主 反応、および移植片拒絶、自己免疫疾患、例えば円板状および全身性の紅斑性狼 瘡、真性糖尿病および自己免疫型慢性皮膚疾患(例えば強皮症および尋常性天疱 瘡)、炎症性疾患、例えばリューマチ様関節炎および喘息、多くの他の病態、例 えば上皮小体機能亢進症(特に、腎不全に伴う続発性の上皮小体機能亢進症)、認 識障害または老人性痴呆(アルツハイマー病)および他の神経変性疾患、高血圧症 、アクネ、脱毛症、皮膚萎縮(例えばステロイド誘発性皮膚萎縮)、皮膚老化(光 老化を包含する)を治療または予防し;骨形成を促進し;骨粗鬆症および骨軟化 症を治療/予防するための薬剤製造のための、請求項1〜5のいずれかの使用。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB9622590.9A GB9622590D0 (en) | 1996-10-30 | 1996-10-30 | Chemical compounds |
GB9622590.9 | 1996-10-30 | ||
PCT/DK1997/000472 WO1998018759A1 (en) | 1996-10-30 | 1997-10-27 | Vitamin d analogues |
Publications (3)
Publication Number | Publication Date |
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JP2001503403A true JP2001503403A (ja) | 2001-03-13 |
JP2001503403A5 JP2001503403A5 (ja) | 2005-07-14 |
JP3907010B2 JP3907010B2 (ja) | 2007-04-18 |
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Application Number | Title | Priority Date | Filing Date |
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JP51993198A Expired - Lifetime JP3907010B2 (ja) | 1996-10-30 | 1997-10-27 | ビタミンd類似体 |
Country Status (21)
Country | Link |
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US (1) | US6310226B1 (ja) |
EP (1) | EP0937038B1 (ja) |
JP (1) | JP3907010B2 (ja) |
KR (1) | KR100526644B1 (ja) |
CN (1) | CN1107669C (ja) |
AT (1) | ATE216361T1 (ja) |
AU (1) | AU722659B2 (ja) |
CA (1) | CA2266479C (ja) |
CZ (1) | CZ290933B6 (ja) |
DE (1) | DE69712086T2 (ja) |
DK (1) | DK0937038T3 (ja) |
ES (1) | ES2173425T3 (ja) |
GB (1) | GB9622590D0 (ja) |
HK (1) | HK1022298A1 (ja) |
HU (1) | HUP9904333A3 (ja) |
NZ (1) | NZ334328A (ja) |
PL (1) | PL192660B1 (ja) |
PT (1) | PT937038E (ja) |
RO (1) | RO120338B1 (ja) |
RU (1) | RU2183622C2 (ja) |
WO (1) | WO1998018759A1 (ja) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2007529433A (ja) * | 2004-03-18 | 2007-10-25 | レオ・ファーマ・アクティーゼルスカブ | ビタミンd類似体の立体選択的合成 |
JP2008538770A (ja) * | 2005-04-25 | 2008-11-06 | サイトクロマ インコーポレイテッド | 1α,25−ジヒドロキシビタミンD3の低血漿カルシウム上昇性16,23−ジエン−25−オキシムアナログ |
Families Citing this family (12)
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WO1999003828A1 (en) * | 1997-07-17 | 1999-01-28 | F.Hoffmann-La Roche Ag | Dihomo-seco-cholestanes with two unsaturated bones in the side chain |
AU2003291810A1 (en) * | 2002-11-18 | 2004-06-15 | Teva Pharmaceutical Industries Ltd. | A crystallization method for purification of calcipotriene |
WO2006051106A1 (en) | 2004-11-12 | 2006-05-18 | Bioxell Spa | Combined use of vitamin d derivatives and anti-proliferative agents for treating bladder cancer |
EP2063963A2 (en) | 2006-08-25 | 2009-06-03 | Cougar Biotechnology, Inc. | Methods for treating cancer comprising the administration of a vitamin d compound and an additional therapeutic agent |
US20080051380A1 (en) | 2006-08-25 | 2008-02-28 | Auerbach Alan H | Methods and compositions for treating cancer |
US20080051375A1 (en) * | 2006-08-25 | 2008-02-28 | Auerbach Alan H | Methods for treating cancer comprising the administration of a vitamin d compound and an additional therapeutic agent, and compositions containing the same |
KR20090039833A (ko) * | 2006-08-29 | 2009-04-22 | 테바 파마슈티컬 인더스트리즈 리미티드 | 비타민 d 및 코르티코스테로이드를 포함하는 약학 조성물 |
SG173119A1 (en) | 2009-01-27 | 2011-08-29 | Berg Biosystems Llc | Vitamin d3 and analogs thereof for alleviating side effects associated with chemotherapy |
US20120184514A1 (en) * | 2009-07-01 | 2012-07-19 | Vitamin Derivatives Inc. | Vitamin d compounds and methods for preparing same |
BR112012003372A2 (pt) | 2009-08-14 | 2019-09-24 | Berg Biosystems Llc | vitamina d3 e análogos da mesma para o tratamento de alopecia. |
EP3003497B1 (en) | 2013-05-29 | 2024-02-14 | BPGbio, Inc. | Preventing or mitigating chemotherapy induced alopecia using vitamin d |
KR20240115925A (ko) | 2016-07-29 | 2024-07-26 | 얀센 파마슈티카 엔브이 | 전립선암의 치료 방법 |
Family Cites Families (10)
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GB8914963D0 (en) * | 1989-06-29 | 1989-08-23 | Leo Pharm Prod Ltd | Chemical compounds |
US5260290A (en) * | 1990-02-14 | 1993-11-09 | Wisconsin Alumni Research Foundation | Homologated vitamin D2 compounds and the corresponding 1α-hydroxylated derivatives |
GB9017890D0 (en) * | 1990-08-15 | 1990-09-26 | Leo Pharm Prod Ltd | Chemical compounds i |
GB9206648D0 (en) * | 1992-03-26 | 1992-05-06 | Leo Pharm Prod Ltd | Chemical compounds |
GB9223061D0 (en) * | 1992-11-04 | 1992-12-16 | Leo Pharm Prod Ltd | Chemical compounds |
US5449668A (en) * | 1993-06-04 | 1995-09-12 | Duphar International Research B.V. | Vitamin D compounds and method of preparing these compounds |
US5552392A (en) * | 1993-11-03 | 1996-09-03 | Wisconsin Alumni Research Foundation | Method of treating hypoparathyroidism with (20S) vitamin D compounds |
JP3228488B2 (ja) | 1993-12-24 | 2001-11-12 | 株式会社クラレ | 20−エピステロイド誘導体およびその製造方法 |
JPH0888281A (ja) * | 1994-09-19 | 1996-04-02 | Fujitsu Ltd | 半導体装置 |
CA2175881A1 (en) * | 1995-05-09 | 1996-11-10 | Andrzej Kutner | Vitamin d compounds and methods of preparing these compounds |
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1996
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1997
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007529433A (ja) * | 2004-03-18 | 2007-10-25 | レオ・ファーマ・アクティーゼルスカブ | ビタミンd類似体の立体選択的合成 |
JP4667450B2 (ja) * | 2004-03-18 | 2011-04-13 | レオ ファーマ アクティーゼルスカブ | ビタミンd類似体の立体選択的合成 |
JP2008538770A (ja) * | 2005-04-25 | 2008-11-06 | サイトクロマ インコーポレイテッド | 1α,25−ジヒドロキシビタミンD3の低血漿カルシウム上昇性16,23−ジエン−25−オキシムアナログ |
Also Published As
Publication number | Publication date |
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PL333068A1 (en) | 1999-11-08 |
CZ135899A3 (cs) | 1999-07-14 |
RU2183622C2 (ru) | 2002-06-20 |
KR100526644B1 (ko) | 2005-11-08 |
ES2173425T3 (es) | 2002-10-16 |
DE69712086D1 (de) | 2002-05-23 |
DE69712086T2 (de) | 2002-11-14 |
ATE216361T1 (de) | 2002-05-15 |
PL192660B1 (pl) | 2006-11-30 |
CN1232448A (zh) | 1999-10-20 |
EP0937038B1 (en) | 2002-04-17 |
GB9622590D0 (en) | 1997-01-08 |
DK0937038T3 (da) | 2002-07-15 |
CA2266479A1 (en) | 1998-05-07 |
HUP9904333A3 (en) | 2001-06-28 |
WO1998018759A1 (en) | 1998-05-07 |
CA2266479C (en) | 2008-09-23 |
RO120338B1 (ro) | 2005-12-30 |
US6310226B1 (en) | 2001-10-30 |
KR20000036233A (ko) | 2000-06-26 |
HUP9904333A2 (hu) | 2000-06-28 |
EP0937038A1 (en) | 1999-08-25 |
JP3907010B2 (ja) | 2007-04-18 |
HK1022298A1 (en) | 2000-08-04 |
AU4771797A (en) | 1998-05-22 |
CN1107669C (zh) | 2003-05-07 |
PT937038E (pt) | 2002-09-30 |
NZ334328A (en) | 2000-09-29 |
CZ290933B6 (cs) | 2002-11-13 |
AU722659B2 (en) | 2000-08-10 |
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