HRP20050198A2 - Piperidin-piridazoni i ftalazoni kao inhibitori pde4 - Google Patents

Piperidin-piridazoni i ftalazoni kao inhibitori pde4

Info

Publication number: HRP20050198A2
Authority: HR; Croatia
Prior art keywords: alkoxy; hydrogen; alkyl; integer; formula
Prior art date: 2002-08-10

Application number

HR20050198A

Other languages

English (en)

Croatian (hr)

Inventor

Hatzelmann Armin

Barsig Johannes

Marx Degenhard

Kley Hans-Peter

A.M. Christiaans Johannes

M.P.B. Menge Wiro

Geert Sterk Jan

Original Assignee

Altana Pharma Ag

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.)

2002-08-10

Filing date

2005-03-01

Publication date

2006-04-30

2005-03-01 Application filed by Altana Pharma Ag filed Critical Altana Pharma Ag

2006-04-30 Publication of HRP20050198A2 publication Critical patent/HRP20050198A2/hr

Links

229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 title claims abstract description 11
239000002587 phosphodiesterase IV inhibitor Substances 0.000 title claims abstract description 11
KHSHUCGBOGKFDA-UHFFFAOYSA-N piperidine;1h-pyridazin-6-one Chemical class C1CCNCC1.O=C1C=CC=NN1 KHSHUCGBOGKFDA-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 157
-1 cinolinyl Chemical group 0.000 claims description 229
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 123
229910052739 hydrogen Inorganic materials 0.000 claims description 123
239000001257 hydrogen Substances 0.000 claims description 123
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 62
150000002431 hydrogen Chemical group 0.000 claims description 57
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 56
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 56
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 56
125000001786 isothiazolyl group Chemical group 0.000 claims description 56
125000002971 oxazolyl group Chemical group 0.000 claims description 56
125000001544 thienyl group Chemical group 0.000 claims description 56
125000000842 isoxazolyl group Chemical group 0.000 claims description 55
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 55
125000000168 pyrrolyl group Chemical group 0.000 claims description 53
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 51
125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 claims description 51
125000001153 fluoro group Chemical group F* 0.000 claims description 50
125000003226 pyrazolyl group Chemical group 0.000 claims description 50
229910052731 fluorine Inorganic materials 0.000 claims description 49
239000011737 fluorine Substances 0.000 claims description 49
125000004432 carbon atom Chemical group C* 0.000 claims description 47
150000003839 salts Chemical class 0.000 claims description 46
125000002541 furyl group Chemical group 0.000 claims description 42
125000002883 imidazolyl group Chemical group 0.000 claims description 42
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 42
125000001041 indolyl group Chemical group 0.000 claims description 42
125000005956 isoquinolyl group Chemical group 0.000 claims description 42
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 42
125000005493 quinolyl group Chemical group 0.000 claims description 42
125000000335 thiazolyl group Chemical group 0.000 claims description 42
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 40
125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 30
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 30
125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 claims description 30
125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 30
125000001624 naphthyl group Chemical group 0.000 claims description 30
125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 30
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 30
125000002098 pyridazinyl group Chemical group 0.000 claims description 30
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
229910052736 halogen Inorganic materials 0.000 claims description 28
125000003373 pyrazinyl group Chemical group 0.000 claims description 28
125000000714 pyrimidinyl group Chemical group 0.000 claims description 28
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 27
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 26
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 23
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 22
125000004433 nitrogen atom Chemical group N* 0.000 claims description 22
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
229910052757 nitrogen Inorganic materials 0.000 claims description 21
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 20
150000002367 halogens Chemical group 0.000 claims description 19
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 19
238000004519 manufacturing process Methods 0.000 claims description 18
239000008194 pharmaceutical composition Substances 0.000 claims description 17
201000010099 disease Diseases 0.000 claims description 16
238000011282 treatment Methods 0.000 claims description 16
238000000034 method Methods 0.000 claims description 15
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 15
125000004076 pyridyl group Chemical group 0.000 claims description 14
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 14
125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 14
125000003118 aryl group Chemical group 0.000 claims description 12
150000002430 hydrocarbons Chemical group 0.000 claims description 12
229910052760 oxygen Inorganic materials 0.000 claims description 12
239000001301 oxygen Substances 0.000 claims description 12
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 11
229910052717 sulfur Inorganic materials 0.000 claims description 11
125000004434 sulfur atom Chemical group 0.000 claims description 11
208000035475 disorder Diseases 0.000 claims description 10
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 10
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
125000005843 halogen group Chemical group 0.000 claims description 9
RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims description 6
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 5
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 5
125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 5
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 4
DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical group C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 3
239000000463 material Substances 0.000 claims description 2
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims 8
SYGWYBOJXOGMRU-UHFFFAOYSA-N chembl233051 Chemical group C1=CC=C2C3=CC(C(N(CCN(C)C)C4=O)=O)=C5C4=CC=CC5=C3SC2=C1 SYGWYBOJXOGMRU-UHFFFAOYSA-N 0.000 claims 5
239000000969 carrier Substances 0.000 claims 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 38
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
239000000203 mixture Substances 0.000 description 27
239000007858 starting material Substances 0.000 description 26
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 24
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
239000000243 solution Substances 0.000 description 20
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
239000002904 solvent Substances 0.000 description 13
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
229910052943 magnesium sulfate Inorganic materials 0.000 description 12
235000019341 magnesium sulphate Nutrition 0.000 description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
230000000694 effects Effects 0.000 description 10
230000005764 inhibitory process Effects 0.000 description 10
238000006243 chemical reaction Methods 0.000 description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 9
239000000546 pharmaceutical excipient Substances 0.000 description 8
239000003112 inhibitor Substances 0.000 description 7
229910000029 sodium carbonate Inorganic materials 0.000 description 7
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QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
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IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 6
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239000002244 precipitate Substances 0.000 description 6
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AFLRARNCCZQUGM-UHFFFAOYSA-N piperidin-4-ylhydrazine;dihydrochloride Chemical compound Cl.Cl.NNC1CCNCC1 AFLRARNCCZQUGM-UHFFFAOYSA-N 0.000 description 4
208000017520 skin disease Diseases 0.000 description 4
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Classifications

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- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings

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Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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Pulmonology (AREA)
Dermatology (AREA)
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Immunology (AREA)
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HR20050198A 2002-08-10 2005-03-01 Piperidin-piridazoni i ftalazoni kao inhibitori pde4 HRP20050198A2 (hr)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP02017977		2002-08-10
PCT/EP2003/008724 WO2004017974A1 (fr)	2002-08-10	2003-08-06	Piperidine-pyridazones et phthalazones en tant qu'inhibiteurs de pde4

Publications (1)

Publication Number	Publication Date
HRP20050198A2 true HRP20050198A2 (hr)	2006-04-30

Family

ID=31896827

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HR20050198A HRP20050198A2 (hr)	2002-08-10	2005-03-01	Piperidin-piridazoni i ftalazoni kao inhibitori pde4

Country Status (18)

Country	Link
US (2)	US20060094710A1 (fr)
EP (2)	EP1556049A1 (fr)
JP (2)	JP4555684B2 (fr)
KR (1)	KR101131684B1 (fr)
CN (1)	CN1671695A (fr)
AT (1)	ATE360627T1 (fr)
AU (2)	AU2003260376A1 (fr)
BR (1)	BR0313330A (fr)
CA (2)	CA2494634A1 (fr)
DE (1)	DE60313472T2 (fr)
ES (1)	ES2286491T3 (fr)
HR (1)	HRP20050198A2 (fr)
IL (1)	IL166271A (fr)
IS (2)	IS2416B (fr)
MX (1)	MXPA05001354A (fr)
PL (2)	PL372926A1 (fr)
RS (1)	RS51445B (fr)
WO (2)	WO2004017974A1 (fr)

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WO2010088335A1 (fr)	2009-01-29	2010-08-05	Novartis Ag	Benzimidazoles substitués destinés au traitement d'astrocytomes
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EP2464649A1 (fr)	2009-08-12	2012-06-20	Novartis AG	Composés hydrazone hétérocycliques et leurs utilisations pour traiter le cancer et l'inflammation
NZ598220A (en)	2009-08-17	2014-02-28	Intellikine Llc	Heterocyclic compounds and uses thereof
MX2012002179A (es)	2009-08-20	2012-03-16	Novartis Ag	Compuestos heterociclicos de oxima.
EP2490687A1 (fr)	2009-10-22	2012-08-29	Vertex Pharmaceuticals Incorporated	Compositions destinées au traitement de la mucoviscidose et d'autres maladies chroniques
US8247436B2 (en)	2010-03-19	2012-08-21	Novartis Ag	Pyridine and pyrazine derivative for the treatment of CF
US8637516B2 (en)	2010-09-09	2014-01-28	Irm Llc	Compounds and compositions as TRK inhibitors
WO2012034095A1 (fr)	2010-09-09	2012-03-15	Irm Llc	Composés et compositions comme inhibiteurs de trk
US8372845B2 (en)	2010-09-17	2013-02-12	Novartis Ag	Pyrazine derivatives as enac blockers
JP2014505088A (ja)	2011-02-10	2014-02-27	ノバルティスアーゲー	Ｃ−ＭＥＴチロシンキナーゼ阻害剤としての［１，２，４］トリアゾロ［４，３−ｂ］ピリダジン化合物
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US8883819B2 (en)	2011-09-01	2014-11-11	Irm Llc	Bicyclic heterocycle derivatives for the treatment of pulmonary arterial hypertension
BR112014006223A8 (pt)	2011-09-15	2018-01-09	Novartis Ag	3-(quinolin-6-iltio)-[1,2,4-triazol[4,3-a] piradinas 6-substituídas, seus usos, composições farmacêuticas, e combinação
US9034879B2 (en)	2011-09-16	2015-05-19	Novartis Ag	Heterocyclic compounds for the treatment of CF
WO2013038381A1 (fr)	2011-09-16	2013-03-21	Novartis Ag	Dérivés d'amide pyridine/pyrazine
WO2013038378A1 (fr)	2011-09-16	2013-03-21	Novartis Ag	Dérivés pyridinamides
WO2013038373A1 (fr)	2011-09-16	2013-03-21	Novartis Ag	Dérivés pyrimidinamides
EP2755652B1 (fr)	2011-09-16	2021-06-02	Novartis AG	Hétérocyclyle carboxamides n-substitués
JP6130391B2 (ja)	2011-11-23	2017-05-17	インテリカイン，エルエルシー	Ｍｔｏｒ阻害剤を使用する強化された治療レジメン
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MX371119B (es)	2012-04-03	2020-01-17	Novartis Ag	Productos de combinacion con los inhibidores de cinasa de tirosina y su uso.
US9073921B2 (en)	2013-03-01	2015-07-07	Novartis Ag	Salt forms of bicyclic heterocyclic derivatives
JP2016512835A (ja)	2013-03-15	2016-05-09	インテリカイン，エルエルシー	キナーゼ阻害剤の組み合わせ及びそれらの使用
TW201605450A (zh)	2013-12-03	2016-02-16	諾華公司	Ｍｄｍ２抑制劑與ＢＲＡＦ抑制劑之組合及其用途
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2003
- 2003-08-06 EP EP03792267A patent/EP1556049A1/fr not_active Withdrawn
- 2003-08-06 CA CA002494634A patent/CA2494634A1/fr not_active Abandoned
- 2003-08-06 RS YUP-2005/0112A patent/RS51445B/en unknown
- 2003-08-06 AT AT03792257T patent/ATE360627T1/de active
- 2003-08-06 AU AU2003260376A patent/AU2003260376A1/en not_active Abandoned
- 2003-08-06 WO PCT/EP2003/008724 patent/WO2004017974A1/fr not_active Application Discontinuation
- 2003-08-06 JP JP2004530086A patent/JP4555684B2/ja not_active Expired - Fee Related
- 2003-08-06 CN CNA038185202A patent/CN1671695A/zh active Pending
- 2003-08-06 AU AU2003258576A patent/AU2003258576B2/en not_active Ceased
- 2003-08-06 US US10/523,111 patent/US20060094710A1/en not_active Abandoned
- 2003-08-06 PL PL03372926A patent/PL372926A1/xx not_active Application Discontinuation
- 2003-08-06 ES ES03792257T patent/ES2286491T3/es not_active Expired - Lifetime
- 2003-08-06 DE DE60313472T patent/DE60313472T2/de not_active Expired - Lifetime
- 2003-08-06 KR KR1020057001920A patent/KR101131684B1/ko not_active IP Right Cessation
- 2003-08-06 PL PL373645A patent/PL214701B1/pl unknown
- 2003-08-06 US US10/523,412 patent/US7220746B2/en not_active Expired - Fee Related
- 2003-08-06 WO PCT/EP2003/008675 patent/WO2004018457A1/fr active IP Right Grant
- 2003-08-06 CA CA2494613A patent/CA2494613C/fr not_active Expired - Fee Related
- 2003-08-06 MX MXPA05001354A patent/MXPA05001354A/es active IP Right Grant
- 2003-08-06 JP JP2004530096A patent/JP2005538140A/ja active Pending
- 2003-08-06 EP EP03792257A patent/EP1537100B1/fr not_active Expired - Lifetime
- 2003-08-06 BR BR0313330-3A patent/BR0313330A/pt not_active Application Discontinuation
2005
- 2005-01-13 IL IL166271A patent/IL166271A/en not_active IP Right Cessation
- 2005-02-28 IS IS7718A patent/IS2416B/is unknown
- 2005-03-01 HR HR20050198A patent/HRP20050198A2/hr not_active Application Discontinuation
- 2005-03-01 IS IS7721A patent/IS7721A/is unknown

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Publication number	Publication date
WO2004018457A1 (fr)	2004-03-04
ATE360627T1 (de)	2007-05-15
JP2006500370A (ja)	2006-01-05
EP1537100A1 (fr)	2005-06-08
EP1556049A1 (fr)	2005-07-27
MXPA05001354A (es)	2005-04-28
KR101131684B1 (ko)	2012-03-28
IL166271A0 (en)	2006-01-15
BR0313330A (pt)	2005-06-14
ES2286491T3 (es)	2007-12-01
DE60313472D1 (de)	2007-06-06
AU2003258576B2 (en)	2009-07-30
IL166271A (en)	2011-02-28
IS7721A (is)	2005-03-01
DE60313472T2 (de)	2008-01-24
CA2494613C (fr)	2011-06-28
PL214701B1 (pl)	2013-09-30
CA2494634A1 (fr)	2004-03-04
CN1671695A (zh)	2005-09-21
KR20050026568A (ko)	2005-03-15
PL372926A1 (en)	2005-08-08
EP1537100B1 (fr)	2007-04-25
RS20050112A (en)	2007-06-04
PL373645A1 (en)	2005-09-05
AU2003258576A1 (en)	2004-03-11
IS7718A (is)	2005-02-28
RS51445B (en)	2011-04-30
JP4555684B2 (ja)	2010-10-06
US20060094710A1 (en)	2006-05-04
WO2004018457A8 (fr)	2004-05-06
WO2004017974A1 (fr)	2004-03-04
JP2005538140A (ja)	2005-12-15
IS2416B (is)	2008-10-15
AU2003260376A1 (en)	2004-03-11
US7220746B2 (en)	2007-05-22
CA2494613A1 (fr)	2004-03-04
US20060160813A1 (en)	2006-07-20

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