ZA200605160B - Pyrrolotriazine compounds as kinase inhibitors - Google Patents

Pyrrolotriazine compounds as kinase inhibitors Download PDF

Info

Publication number: ZA200605160B
Authority: ZA; South Africa
Prior art keywords: amino; methyl; triazin; pyrrolo; compound
Prior art date: 2003-12-29

Application number

ZA200605160A

Other languages

English (en)

Inventor

Brian E Fink

Ashvinikumar V Gavai

Gregory D Vite

Chen Ping

Mastalerz Harold

Derek J Norris

John S Tokarski

Zhao Yufen

Han Wen-Ching

Original Assignee

Bristol Myers Squibb Co

Priority date (The priority date 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 date listed.)

2003-12-29

Filing date

2006-06-22

Publication date

2007-12-27

2006-06-22 Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co

2007-12-27 Publication of ZA200605160B publication Critical patent/ZA200605160B/en

Links

229940043355 kinase inhibitor Drugs 0.000 title claims description 6
239000003757 phosphotransferase inhibitor Substances 0.000 title claims description 6
150000003921 pyrrolotriazines Chemical class 0.000 title description 6
150000001875 compounds Chemical class 0.000 claims description 553
OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 470
-1 4-Amino-1-piperidinyl Chemical group 0.000 claims description 264
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 162
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 153
239000000203 mixture Substances 0.000 claims description 134
QQOWHRYOXYEMTL-UHFFFAOYSA-N triazin-4-amine Chemical compound N=C1C=CN=NN1 QQOWHRYOXYEMTL-UHFFFAOYSA-N 0.000 claims description 75
BIWOSRSKDCZIFM-UHFFFAOYSA-N piperidin-3-ol Chemical compound OC1CCCNC1 BIWOSRSKDCZIFM-UHFFFAOYSA-N 0.000 claims description 70
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 62
238000000034 method Methods 0.000 claims description 44
229910052739 hydrogen Inorganic materials 0.000 claims description 43
125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 41
125000000217 alkyl group Chemical group 0.000 claims description 33
VSPXQZSDPSOPRO-UHFFFAOYSA-N pyrrolo[2,1-f][1,2,4]triazin-4-amine Chemical compound NC1=NC=NN2C=CC=C12 VSPXQZSDPSOPRO-UHFFFAOYSA-N 0.000 claims description 26
239000001257 hydrogen Substances 0.000 claims description 25
150000003839 salts Chemical class 0.000 claims description 24
125000003118 aryl group Chemical group 0.000 claims description 23
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125000000623 heterocyclic group Chemical group 0.000 claims description 21
LKLQWOKKPWCIAW-UHFFFAOYSA-N piperidin-3-yl carbamate Chemical compound NC(=O)OC1CCCNC1 LKLQWOKKPWCIAW-UHFFFAOYSA-N 0.000 claims description 21
108091000080 Phosphotransferase Proteins 0.000 claims description 19
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QCQKTGJRAPFKRX-UHFFFAOYSA-N piperidine-3,5-diol Chemical compound OC1CNCC(O)C1 QCQKTGJRAPFKRX-UHFFFAOYSA-N 0.000 claims description 14
125000000714 pyrimidinyl group Chemical group 0.000 claims description 14
125000003107 substituted aryl group Chemical group 0.000 claims description 14
150000002431 hydrogen Chemical class 0.000 claims description 13
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
- 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
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
- 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
- A61P17/06—Antipsoriatics
- 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
- A61P35/00—Antineoplastic agents
- 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

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Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
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ZA200605160A 2003-12-29 2006-06-22 Pyrrolotriazine compounds as kinase inhibitors ZA200605160B (en)

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US53333503P	2003-12-29	2003-12-29

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ZA200605160B true ZA200605160B (en)	2007-12-27

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ZA200605160A ZA200605160B (en)	2003-12-29	2006-06-22	Pyrrolotriazine compounds as kinase inhibitors

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US (4)	US7141571B2 (sl)
EP (2)	EP2058314A1 (sl)
JP (1)	JP4740878B2 (sl)
KR (1)	KR100839716B1 (sl)
CN (1)	CN1922182B (sl)
AR (1)	AR047076A1 (sl)
AT (1)	ATE443706T1 (sl)
AU (1)	AU2004312413C1 (sl)
BR (1)	BRPI0418231A (sl)
CA (1)	CA2552107C (sl)
CL (1)	CL2009001492A1 (sl)
CY (1)	CY1109662T1 (sl)
DE (1)	DE602004023324D1 (sl)
DK (1)	DK1699797T3 (sl)
ES (1)	ES2331842T3 (sl)
GE (1)	GEP20105081B (sl)
HK (1)	HK1088332A1 (sl)
HR (1)	HRP20090601T1 (sl)
IL (1)	IL176450A0 (sl)
MX (1)	MXPA06007038A (sl)
MY (1)	MY145634A (sl)
NO (1)	NO20062763L (sl)
NZ (2)	NZ548070A (sl)
PE (1)	PE20050679A1 (sl)
PL (1)	PL1699797T3 (sl)
PT (1)	PT1699797E (sl)
RU (1)	RU2373209C2 (sl)
SI (1)	SI1699797T1 (sl)
TW (1)	TWI332840B (sl)
UA (1)	UA89038C2 (sl)
WO (1)	WO2005066176A1 (sl)
ZA (1)	ZA200605160B (sl)

Families Citing this family (38)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6867300B2 (en) *	2000-11-17	2005-03-15	Bristol-Myers Squibb Company	Methods for the preparation of pyrrolotriazine compounds useful as kinase inhibitors
GEP20074148B (en) *	2002-04-23	2007-07-10	Bristol Myers Squibb Co	Pyrrolo-triazine aniline compounds useful as kinase inhibitors
US20060014741A1 (en) *	2003-12-12	2006-01-19	Dimarco John D	Synthetic process, and crystalline forms of a pyrrolotriazine compound
MY145634A (en) *	2003-12-29	2012-03-15	Bristol Myers Squibb Co	Pyrrolotriazine compounds as kinase inhibitors
US7102002B2 (en)	2004-06-16	2006-09-05	Bristol-Myers Squibb Company	Pyrrolotriazine kinase inhibitors
US7173031B2 (en) *	2004-06-28	2007-02-06	Bristol-Myers Squibb Company	Pyrrolotriazine kinase inhibitors
US7253167B2 (en) *	2004-06-30	2007-08-07	Bristol-Myers Squibb Company	Tricyclic-heteroaryl compounds useful as kinase inhibitors
TW200600513A (en) *	2004-06-30	2006-01-01	Bristol Myers Squibb Co	A method for preparing pyrrolotriazine compounds
US7504521B2 (en) *	2004-08-05	2009-03-17	Bristol-Myers Squibb Co.	Methods for the preparation of pyrrolotriazine compounds
PE20060421A1 (es)	2004-08-12	2006-06-01	Bristol Myers Squibb Co	Procedimiento para preparar un compuesto de pirrolotriazina anilina como inhibidores de cinasa
TW200635927A (en) *	2004-12-22	2006-10-16	Bristol Myers Squibb Co	Synthetic process
US7358256B2 (en)	2005-03-28	2008-04-15	Bristol-Myers Squibb Company	ATP competitive kinase inhibitors
US20060235020A1 (en) *	2005-04-18	2006-10-19	Soojin Kim	Process for preparing salts of 4-[[5-[(cyclopropylamino)carbonyl]-2-methylphenyl]amino]-5-methyl-N-propylpyrrolo[2,1-f][1,2,4]triazine-6-carboxamide and novel stable forms produced therein
MY150958A (en)	2005-06-16	2014-03-31	Astrazeneca Ab	Compounds for the treatment of multi-drug resistant bacterial infections
JP5193876B2 (ja) *	2005-12-02	2013-05-08	バイエル・ヘルスケア・エルエルシー	オーロラキナーゼの阻害により癌を処置するために有用なピロロトリアジン誘導体
US8063208B2 (en) *	2006-02-16	2011-11-22	Bristol-Myers Squibb Company	Crystalline forms of (3R,4R)-4-amino-1-[[4-[(3-methoxyphenyl)amino]pyrrolo[2,1-f][1,2,4]triazin-5-yl]methyl]piperidin-3-ol
US20100136137A1 (en) *	2006-11-01	2010-06-03	Bristol-Meyers Squibb Company	Therapeutic combination of a panher/vegfr2 kinase inhibitor and a platinum compound
WO2008103248A1 (en)	2007-02-08	2008-08-28	Codexis, Inc.	Ketoreductases and uses thereof
US20090076034A1 (en) *	2007-09-14	2009-03-19	Protia, Llc	Deuterium-enriched bms-690514
RU2498985C2 (ru) *	2007-12-19	2013-11-20	Дженентек, Инк.	8-анилиноимидазопиридины и способы их использования
JP2010209058A (ja) *	2008-09-29	2010-09-24	Sumitomo Chemical Co Ltd	１−置換−トランス−４−（置換アミノ）ピペリジン−３−オールの製造方法
CN102245610B (zh) *	2008-10-08	2014-04-30	百时美施贵宝公司	吡咯并三嗪激酶抑制剂
EP2376491B1 (en)	2008-12-19	2015-03-04	Cephalon, Inc.	Pyrrolotriazines as alk and jak2 inhibitors
JP5662346B2 (ja)	2009-01-21	2015-01-28	バジリアファルマスーチカアーゲーＢａｓｉｌｅａＰｈａｒｍａｃｅｕｔｉｃａＡＧ	新規二環式抗生物質
IN2012DN01251A (sl) *	2009-07-28	2015-05-15	Ube Industries
ES2550667T3 (es)	2010-02-18	2015-11-11	Vtv Therapeutics Llc	Derivados de fenilheteroarilo y métodos de uso de los mismos
ES2689103T3 (es)	2010-06-30	2018-11-08	Fujifilm Corporation	Nuevo derivado de nicotinamida o sal del mismo
CN102153558B (zh) *	2011-02-23	2012-11-21	扬州永济医药新技术有限公司	多靶点抗肿瘤抑制剂2-氨吡咯-三嗪的衍生物及其合成方法
DE102011119127A1 (de) *	2011-11-22	2013-05-23	Merck Patent Gmbh	3-Cyanaryl-1H-pyrrolo[2.3-b]pyridin-Derivate
US9724352B2 (en)	2012-05-31	2017-08-08	Shanghai Institute Of Materia Medica, Chinese Academy Of Sciences	Pyrrolo[2,1-F[1,2,4]triazine compounds, preparation methods and applications thereof
CN103450204B (zh)	2012-05-31	2016-08-17	中国科学院上海药物研究所	吡咯[2，1-f][1，2，4]并三嗪类化合物，其制备方法及用途
TW201414737A (zh)	2012-07-13	2014-04-16	必治妥美雅史谷比公司	作爲激酶抑制劑之咪唑并三□甲腈
CN105979950A (zh)	2013-10-11	2016-09-28	百时美施贵宝公司	吡咯并三嗪激酶抑制剂
DK3094329T3 (en) *	2014-01-13	2018-11-19	Aurigene Discovery Tech Ltd	BICYCLIC HETEROCYCLYL DERIVATIVES AS IRAC4 INHIBITORS
US9459267B2 (en) *	2014-05-12	2016-10-04	Quest Diagnostics Investments Incorporated	Quantitation of tamoxifen and metabolites thereof by mass spectrometry
AR112027A1 (es)	2017-06-15	2019-09-11	Biocryst Pharm Inc	Inhibidores de alk 2 quinasa que contienen imidazol
JP7276719B2 (ja) *	2018-05-08	2023-05-18	メッドシャインディスカバリーインコーポレイテッド	選択的ＨＥＲ２阻害剤としてのピロロ［２，１－ｆ］［１，２，４］トリアジン系誘導体及びその使用
WO2021088987A1 (zh) *	2019-11-08	2021-05-14	南京明德新药研发有限公司	作为选择性her2抑制剂的盐型、晶型及其应用

Family Cites Families (23)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA2163399A1 (en)	1994-11-24	1996-05-25	Katsuhiro Kawano	Triazine derivative, chymase activity inhibitor and nitric oxide production inhibitor
AU735401B2 (en)	1996-08-28	2001-07-05	Pfizer Inc.	Substituted 6,5-hetero-bicyclic derivatives
WO2000071129A1 (en) *	1999-05-21	2000-11-30	Bristol-Myers Squibb Company	Pyrrolotriazine inhibitors of kinases
US6982265B1 (en)	1999-05-21	2006-01-03	Bristol Myers Squibb Company	Pyrrolotriazine inhibitors of kinases
WO2001014378A1 (fr) *	1999-08-23	2001-03-01	Shionogi & Co., Ltd.	DERIVES DE PYRROLOTRIAZINE A ACTIVITES INHIBANT sPLA¿2?
US6867300B2 (en) *	2000-11-17	2005-03-15	Bristol-Myers Squibb Company	Methods for the preparation of pyrrolotriazine compounds useful as kinase inhibitors
US6670357B2 (en) *	2000-11-17	2003-12-30	Bristol-Myers Squibb Company	Methods of treating p38 kinase-associated conditions and pyrrolotriazine compounds useful as kinase inhibitors
PL366376A1 (en)	2000-11-17	2005-01-24	Bristol-Myers Squibb Company	Methods of treating p38 kinase-associated conditions and pyrrolotriazine compounds useful as kinase inhibitors
TW200300350A (en) *	2001-11-14	2003-06-01	Bristol Myers Squibb Co	C-5 modified indazolylpyrrolotriazines
GEP20074148B (en)	2002-04-23	2007-07-10	Bristol Myers Squibb Co	Pyrrolo-triazine aniline compounds useful as kinase inhibitors
JP2005529890A (ja) *	2002-04-23	2005-10-06	ブリストル−マイヤーズ　スクイブ　カンパニー	キナーゼ阻害剤として有用なアリールケトンピロロトリアジン化合物
US6894066B2 (en)	2002-05-09	2005-05-17	Bernard Charles Sherman	Magnesium salt of S-omeprazole
TW200407143A (en)	2002-05-21	2004-05-16	Bristol Myers Squibb Co	Pyrrolotriazinone compounds and their use to treat diseases
TWI329112B (en) *	2002-07-19	2010-08-21	Bristol Myers Squibb Co	Novel inhibitors of kinases
TWI272271B (en)	2002-07-19	2007-02-01	Bristol Myers Squibb Co	Process for preparing certain pyrrolotriazine compounds
EP1543009A4 (en)	2002-08-02	2007-08-08	Bristol Myers Squibb Co	Pyrrolotriazine KINASE INHIBITORS
TW200420565A (en) *	2002-12-13	2004-10-16	Bristol Myers Squibb Co	C-6 modified indazolylpyrrolotriazines
US7102001B2 (en) *	2003-12-12	2006-09-05	Bristol-Myers Squibb Company	Process for preparing pyrrolotriazine
US7064203B2 (en) *	2003-12-29	2006-06-20	Bristol Myers Squibb Company	Di-substituted pyrrolotriazine compounds
MY145634A (en)	2003-12-29	2012-03-15	Bristol Myers Squibb Co	Pyrrolotriazine compounds as kinase inhibitors
US7102002B2 (en) *	2004-06-16	2006-09-05	Bristol-Myers Squibb Company	Pyrrolotriazine kinase inhibitors
US7102003B2 (en) *	2004-07-01	2006-09-05	Bristol-Myers Squibb Company	Pyrrolotriazine compounds
US7151176B2 (en)	2004-10-21	2006-12-19	Bristol-Myers Squibb Company	Pyrrolotriazine compounds

2004
- 2004-12-09 MY MYPI20045093A patent/MY145634A/en unknown
- 2004-12-22 US US11/019,901 patent/US7141571B2/en active Active
- 2004-12-22 TW TW093140035A patent/TWI332840B/zh not_active IP Right Cessation
- 2004-12-23 DE DE602004023324T patent/DE602004023324D1/de active Active
- 2004-12-23 NZ NZ548070A patent/NZ548070A/en unknown
- 2004-12-23 WO PCT/US2004/043169 patent/WO2005066176A1/en active Application Filing
- 2004-12-23 JP JP2006547328A patent/JP4740878B2/ja not_active Expired - Fee Related
- 2004-12-23 CA CA2552107A patent/CA2552107C/en not_active Expired - Fee Related
- 2004-12-23 MX MXPA06007038A patent/MXPA06007038A/es active IP Right Grant
- 2004-12-23 RU RU2006127396/04A patent/RU2373209C2/ru not_active IP Right Cessation
- 2004-12-23 PL PL04815269T patent/PL1699797T3/pl unknown
- 2004-12-23 GE GEAP20049544A patent/GEP20105081B/en unknown
- 2004-12-23 SI SI200431286T patent/SI1699797T1/sl unknown
- 2004-12-23 PT PT04815269T patent/PT1699797E/pt unknown
- 2004-12-23 NZ NZ573544A patent/NZ573544A/en unknown
- 2004-12-23 AT AT04815269T patent/ATE443706T1/de active
- 2004-12-23 EP EP09153694A patent/EP2058314A1/en not_active Withdrawn
- 2004-12-23 CN CN2004800421984A patent/CN1922182B/zh not_active Expired - Fee Related
- 2004-12-23 AU AU2004312413A patent/AU2004312413C1/en not_active Ceased
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- 2004-12-23 KR KR1020067012936A patent/KR100839716B1/ko not_active IP Right Cessation
- 2004-12-23 UA UAA200608400A patent/UA89038C2/ru unknown
- 2004-12-23 BR BRPI0418231-6A patent/BRPI0418231A/pt not_active IP Right Cessation
- 2004-12-23 EP EP04815269A patent/EP1699797B1/en active Active
- 2004-12-23 DK DK04815269T patent/DK1699797T3/da active
- 2004-12-29 AR ARP040104947A patent/AR047076A1/es not_active Application Discontinuation
2005
- 2005-01-03 PE PE2005000015A patent/PE20050679A1/es not_active Application Discontinuation
2006
- 2006-06-13 NO NO20062763A patent/NO20062763L/no not_active Application Discontinuation
- 2006-06-20 IL IL176450A patent/IL176450A0/en unknown
- 2006-06-22 ZA ZA200605160A patent/ZA200605160B/en unknown
- 2006-06-26 US US11/426,479 patent/US7297695B2/en active Active
- 2006-09-19 HK HK06110373.0A patent/HK1088332A1/xx not_active IP Right Cessation
2008
- 2008-09-24 US US11/869,910 patent/US7846931B2/en active Active
2009
- 2009-06-26 CL CL2009001492A patent/CL2009001492A1/es unknown
- 2009-11-09 HR HR20090601T patent/HRP20090601T1/hr unknown
- 2009-12-21 CY CY20091101326T patent/CY1109662T1/el unknown
2010
- 2010-10-25 US US12/911,299 patent/US20110039838A1/en not_active Abandoned

Also Published As

Publication number	Publication date
BRPI0418231A (pt)	2007-04-27
RU2373209C2 (ru)	2009-11-20
PE20050679A1 (es)	2005-09-25
AU2004312413C1 (en)	2011-01-27
TW200526226A (en)	2005-08-16
RU2006127396A (ru)	2008-02-10
HRP20090601T1 (hr)	2009-12-31
JP2007518721A (ja)	2007-07-12
CA2552107A1 (en)	2005-07-21
AU2004312413A1 (en)	2005-07-21
SI1699797T1 (sl)	2010-04-30
NZ573544A (en)	2010-04-30
DK1699797T3 (da)	2010-01-04
AU2004312413B2 (en)	2010-07-22
ES2331842T3 (es)	2010-01-18
PT1699797E (pt)	2009-12-29
NO20062763L (no)	2006-09-11
US20090048244A1 (en)	2009-02-19
WO2005066176A1 (en)	2005-07-21
PL1699797T3 (pl)	2010-02-26
MXPA06007038A (es)	2006-08-31
EP1699797A1 (en)	2006-09-13
GEP20105081B (en)	2010-09-27
IL176450A0 (en)	2006-10-05
CN1922182B (zh)	2010-08-18
US7846931B2 (en)	2010-12-07
KR100839716B1 (ko)	2008-06-19
US20110039838A1 (en)	2011-02-17
EP2058314A1 (en)	2009-05-13
NZ548070A (en)	2009-02-28
JP4740878B2 (ja)	2011-08-03
MY145634A (en)	2012-03-15
ATE443706T1 (de)	2009-10-15
CL2009001492A1 (es)	2010-01-15
CA2552107C (en)	2011-10-18
AR047076A1 (es)	2006-01-04
US20050182058A1 (en)	2005-08-18
HK1088332A1 (en)	2006-11-03
UA89038C2 (en)	2009-12-25
US20060264438A1 (en)	2006-11-23
US7141571B2 (en)	2006-11-28
CY1109662T1 (el)	2014-08-13
EP1699797B1 (en)	2009-09-23
TWI332840B (en)	2010-11-11
DE602004023324D1 (de)	2009-11-05
CN1922182A (zh)	2007-02-28
KR20060107828A (ko)	2006-10-16
US7297695B2 (en)	2007-11-20