ZA200105921B - Substituted 1-(4-piperidyl)-3-(aryl)isothioureas their preparation and therapeutic application. - Google Patents

Substituted 1-(4-piperidyl)-3-(aryl)isothioureas their preparation and therapeutic application. Download PDF

Info

Publication number: ZA200105921B
Authority: ZA; South Africa
Prior art keywords: piperidyl; benzothiazin; methyl; amine; hydrogen fumarate
Prior art date: 1999-01-22

Application number

ZA200105921A

Other languages

English (en)

Inventor

Jean-Pierre Rieu

Jean-Francois Patoiseau

Gareth John

Bruno Legrand

Yvan Verscheure

Original Assignee

Pf Medicament

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.)

1999-01-22

Filing date

2001-07-18

Publication date

2002-05-08

2001-07-18 Application filed by Pf Medicament filed Critical Pf Medicament

2002-05-08 Publication of ZA200105921B publication Critical patent/ZA200105921B/en

Links

238000002360 preparation method Methods 0.000 title abstract description 8
230000001225 therapeutic effect Effects 0.000 title abstract description 6
150000002541 isothioureas Chemical class 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 72
239000000203 mixture Substances 0.000 claims abstract description 27
-1 nitro, hydroxy Chemical group 0.000 claims abstract description 23
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 19
150000003839 salts Chemical class 0.000 claims abstract description 12
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 10
239000001257 hydrogen Substances 0.000 claims abstract description 10
229910052500 inorganic mineral Inorganic materials 0.000 claims abstract description 10
239000011707 mineral Substances 0.000 claims abstract description 10
229920006395 saturated elastomer Polymers 0.000 claims abstract description 8
241000534944 Thia Species 0.000 claims abstract description 4
229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
239000001301 oxygen Substances 0.000 claims abstract description 4
125000002252 acyl group Chemical group 0.000 claims abstract description 3
125000004423 acyloxy group Chemical group 0.000 claims abstract description 3
125000003545 alkoxy group Chemical group 0.000 claims abstract description 3
125000005843 halogen group Chemical group 0.000 claims abstract description 3
150000004677 hydrates Chemical class 0.000 claims abstract description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 3
125000004417 unsaturated alkyl group Chemical group 0.000 claims abstract description 3
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract 2
VZCYOOQTPOCHFL-OWOJBTEDSA-M fumarate(1-) Chemical compound OC(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-M 0.000 claims description 99
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 28
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 28
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 18
208000028867 ischemia Diseases 0.000 claims description 9
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 6
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 6
150000001412 amines Chemical class 0.000 claims description 6
229940126601 medicinal product Drugs 0.000 claims description 5
239000002904 solvent Substances 0.000 claims description 5
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 4
NBYQXBYMEUOBON-UHFFFAOYSA-N carbamothioyl chloride Chemical compound NC(Cl)=S NBYQXBYMEUOBON-UHFFFAOYSA-N 0.000 claims description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
VYFOAVADNIHPTR-UHFFFAOYSA-N isatoic anhydride Chemical compound NC1=CC=CC=C1CO VYFOAVADNIHPTR-UHFFFAOYSA-N 0.000 claims description 4
125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 4
206010019280 Heart failures Diseases 0.000 claims description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
208000019695 Migraine disease Diseases 0.000 claims description 3
208000002193 Pain Diseases 0.000 claims description 3
206010015037 epilepsy Diseases 0.000 claims description 3
150000002431 hydrogen Chemical class 0.000 claims description 3
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208000031225 myocardial ischemia Diseases 0.000 claims description 3
ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 claims description 3
125000005975 2-phenylethyloxy group Chemical group 0.000 claims description 2
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 2
206010020772 Hypertension Diseases 0.000 claims description 2
206010038563 Reocclusion Diseases 0.000 claims description 2
208000007718 Stable Angina Diseases 0.000 claims description 2
125000002102 aryl alkyloxo group Chemical group 0.000 claims description 2
125000004663 dialkyl amino group Chemical group 0.000 claims description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 2
229910052717 sulfur Inorganic materials 0.000 claims description 2
125000004434 sulfur atom Chemical group 0.000 claims description 2
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
239000008194 pharmaceutical composition Substances 0.000 claims 2
LNPWQGVVOPPMFG-UHFFFAOYSA-N C(C=CC(=O)O)(=O)O.N1=C(SCC2=C1C=CC=C2)N Chemical compound C(C=CC(=O)O)(=O)O.N1=C(SCC2=C1C=CC=C2)N LNPWQGVVOPPMFG-UHFFFAOYSA-N 0.000 claims 1
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230000002490 cerebral effect Effects 0.000 claims 1
201000010099 disease Diseases 0.000 claims 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
239000003814 drug Substances 0.000 claims 1
BLYDPDXBRDQGQJ-UHFFFAOYSA-N hydroxymethylsulfanylurea Chemical compound NC(=O)NSCO BLYDPDXBRDQGQJ-UHFFFAOYSA-N 0.000 claims 1
230000000302 ischemic effect Effects 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
DQVIJGNWWFOCMI-UHFFFAOYSA-N n-methyl-n-[1-[3-(2-phenylethoxy)propyl]piperidin-4-yl]-4h-3,1-benzothiazin-2-amine Chemical compound N=1C2=CC=CC=C2CSC=1N(C)C(CC1)CCN1CCCOCCC1=CC=CC=C1 DQVIJGNWWFOCMI-UHFFFAOYSA-N 0.000 claims 1
239000000546 pharmaceutical excipient Substances 0.000 claims 1
229940124531 pharmaceutical excipient Drugs 0.000 claims 1
230000000069 prophylactic effect Effects 0.000 claims 1
238000001953 recrystallisation Methods 0.000 claims 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract 1
125000003282 alkyl amino group Chemical group 0.000 abstract 1
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 93
239000013078 crystal Substances 0.000 description 41
238000002844 melting Methods 0.000 description 33
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238000000034 method Methods 0.000 description 32
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239000000243 solution Substances 0.000 description 25
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239000012230 colorless oil Substances 0.000 description 18
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238000009835 boiling Methods 0.000 description 14
238000003756 stirring Methods 0.000 description 13
239000002585 base Substances 0.000 description 12
238000006243 chemical reaction Methods 0.000 description 12
PVFOHMXILQEIHX-UHFFFAOYSA-N 8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9-[2-(2-bromophenyl)ethyl]purin-6-amine Chemical compound C=1C=2OCOC=2C=C(Br)C=1SC1=NC=2C(N)=NC=NC=2N1CCC1=CC=CC=C1Br PVFOHMXILQEIHX-UHFFFAOYSA-N 0.000 description 11
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125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 11
239000000843 powder Substances 0.000 description 10
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
239000012267 brine Substances 0.000 description 9
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
AUWDOZOUJWEPBA-UHFFFAOYSA-N 2-(4-methoxyphenyl)ethanol Chemical compound COC1=CC=C(CCO)C=C1 AUWDOZOUJWEPBA-UHFFFAOYSA-N 0.000 description 8
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SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 8
235000010755 mineral Nutrition 0.000 description 8
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ZPJVBXZAAXMKIO-WLHGVMLRSA-N (e)-but-2-enedioic acid;n-[1-[4-[(4-fluorophenyl)methoxy]butyl]piperidin-4-yl]-n-methyl-4h-3,1-benzothiazin-2-amine Chemical compound OC(=O)\C=C\C(O)=O.N=1C2=CC=CC=C2CSC=1N(C)C(CC1)CCN1CCCCOCC1=CC=C(F)C=C1 ZPJVBXZAAXMKIO-WLHGVMLRSA-N 0.000 description 7
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239000000706 filtrate Substances 0.000 description 7
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238000007126 N-alkylation reaction Methods 0.000 description 6
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150000004985 diamines Chemical class 0.000 description 3
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OHEDMAIVEXQCOZ-UHFFFAOYSA-N piperidine;dihydrochloride Chemical compound Cl.Cl.C1CCNCC1 OHEDMAIVEXQCOZ-UHFFFAOYSA-N 0.000 description 1
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XJVIPPHGDPEDJL-UHFFFAOYSA-N thiourea;hydrochloride Chemical compound Cl.NC(N)=S XJVIPPHGDPEDJL-UHFFFAOYSA-N 0.000 description 1
201000010875 transient cerebral ischemia Diseases 0.000 description 1
125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
- 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
- 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
- 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
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—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
- C07D417/02—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
- C07D417/12—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 chain containing hetero atoms as chain links

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Cardiology (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Heart & Thoracic Surgery (AREA)
Neurology (AREA)
Pain & Pain Management (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Hospice & Palliative Care (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Peptides Or Proteins (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)

ZA200105921A 1999-01-22 2001-07-18 Substituted 1-(4-piperidyl)-3-(aryl)isothioureas their preparation and therapeutic application. ZA200105921B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
FR9900706A FR2788775B1 (fr)	1999-01-22	1999-01-22	Nouvelles n-alcoyl-n-[1-(omega-(arylalcoyloxy)alcoyl] piperidin-4-yl]-4h-3,1-benzo(thia/oxa)zines-2-amines substituees, leur preparation et leur application en therapeutique

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Publication Number	Publication Date
ZA200105921B true ZA200105921B (en)	2002-05-08

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ZA200105921A ZA200105921B (en)	1999-01-22	2001-07-18	Substituted 1-(4-piperidyl)-3-(aryl)isothioureas their preparation and therapeutic application.

Country Status (15)

Country	Link
US (1)	US6531469B1 (es)
EP (1)	EP1144408B1 (es)
JP (1)	JP2002535329A (es)
CN (1)	CN1129599C (es)
AT (1)	ATE224892T1 (es)
AU (1)	AU767132B2 (es)
BR (1)	BR0007674A (es)
CA (1)	CA2359103A1 (es)
DE (1)	DE60000500T2 (es)
DK (1)	DK1144408T3 (es)
ES (1)	ES2182770T3 (es)
FR (1)	FR2788775B1 (es)
PT (1)	PT1144408E (es)
WO (1)	WO2000043391A1 (es)
ZA (1)	ZA200105921B (es)

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WO1990003118A1 (en) *	1988-09-29	1990-04-05	Meheco Proprietary Limited	Meat preservation
EP0982300A3 (en) *	1998-07-29	2000-03-08	Societe Civile Bioprojet	Non-imidazole alkylamines as histamine H3 - receptor ligands and their therapeutic applications
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1999
- 1999-01-22 FR FR9900706A patent/FR2788775B1/fr not_active Expired - Fee Related
2000
- 2000-01-21 WO PCT/FR2000/000137 patent/WO2000043391A1/fr active IP Right Grant
- 2000-01-21 US US09/889,805 patent/US6531469B1/en not_active Expired - Fee Related
- 2000-01-21 CA CA002359103A patent/CA2359103A1/fr not_active Abandoned
- 2000-01-21 ES ES00900639T patent/ES2182770T3/es not_active Expired - Lifetime
- 2000-01-21 CN CN00805327A patent/CN1129599C/zh not_active Expired - Fee Related
- 2000-01-21 AT AT00900639T patent/ATE224892T1/de not_active IP Right Cessation
- 2000-01-21 JP JP2000594807A patent/JP2002535329A/ja active Pending
- 2000-01-21 AU AU30581/00A patent/AU767132B2/en not_active Ceased
- 2000-01-21 DK DK00900639T patent/DK1144408T3/da active
- 2000-01-21 PT PT00900639T patent/PT1144408E/pt unknown
- 2000-01-21 EP EP00900639A patent/EP1144408B1/fr not_active Expired - Lifetime
- 2000-01-21 BR BR0007674-0A patent/BR0007674A/pt not_active Application Discontinuation
- 2000-01-21 DE DE60000500T patent/DE60000500T2/de not_active Expired - Fee Related
2001
- 2001-07-18 ZA ZA200105921A patent/ZA200105921B/en unknown

Also Published As

Publication number	Publication date
ES2182770T3 (es)	2003-03-16
US6531469B1 (en)	2003-03-11
DE60000500D1 (de)	2002-10-31
AU767132B2 (en)	2003-10-30
EP1144408A1 (fr)	2001-10-17
AU3058100A (en)	2000-08-07
JP2002535329A (ja)	2002-10-22
DK1144408T3 (da)	2003-02-03
WO2000043391A1 (fr)	2000-07-27
FR2788775A1 (fr)	2000-07-28
EP1144408B1 (fr)	2002-09-25
BR0007674A (pt)	2001-11-20
PT1144408E (pt)	2003-02-28
ATE224892T1 (de)	2002-10-15
CA2359103A1 (fr)	2000-07-27
FR2788775B1 (fr)	2001-04-13
DE60000500T2 (de)	2003-07-31
CN1344267A (zh)	2002-04-10
CN1129599C (zh)	2003-12-03

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