ECSP034446A - Derivados de 4-fenil-piridon como antagonistas receptores de neuroquinina 1 - Google Patents

Derivados de 4-fenil-piridon como antagonistas receptores de neuroquinina 1

Info

Publication number
ECSP034446A
ECSP034446A EC2003004446A ECSP034446A ECSP034446A EC SP034446 A ECSP034446 A EC SP034446A EC 2003004446 A EC2003004446 A EC 2003004446A EC SP034446 A ECSP034446 A EC SP034446A EC SP034446 A ECSP034446 A EC SP034446A
Authority
EC
Ecuador
Prior art keywords
piridon
neuroquinina
antagonists
phenyl
derivatives
Prior art date
Application number
EC2003004446A
Other languages
English (en)
Inventor
Torsten Hoffmann
Original Assignee
Hoffmann La Roche
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.)
Filing date
Publication date
Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche
Publication of ECSP034446A publication Critical patent/ECSP034446A/es

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72Nitrogen atoms
    • C07D213/75Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/08Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/02Nasal agents, e.g. decongestants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/06Antiasthmatics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/02Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/06Antimigraine agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/14Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16Anti-Parkinson drugs
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/22Anxiolytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/24Antidepressants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/30Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/36Opioid-abuse
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81Amides; Imides
    • C07D213/82Amides; Imides in position 3
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D231/00Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D233/00Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/56Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D249/00Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/081,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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 two hetero rings
    • C07D401/04Heterocyclic 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 two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic 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
    • C07D413/04Heterocyclic 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 directly linked by a ring-member-to-ring-member bond

Abstract

El invento se refiere a compuestos de las fórmulas generales es donde R1 es o es -NH(CH2)2OH,-NR3C(O)-ciclopropilo; R2 es metilo o cloro; R3 es hidrógeno o metilo; R es hidrógeno o -(CH2)2OH; y n es 1 o 2 y sus sales de adición de ácido farmacéutica mente aceptables. Estos compuestos tienen buena afinidad al receptor de NK-1 y por tanto pueden utilizarse en el tratamiento o prevención de enfermedades relacionadas con este receptor.
EC2003004446A 2000-07-24 2003-01-23 Derivados de 4-fenil-piridon como antagonistas receptores de neuroquinina 1 ECSP034446A (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP00115846 2000-07-24

Publications (1)

Publication Number Publication Date
ECSP034446A true ECSP034446A (es) 2003-03-10

Family

ID=8169331

Family Applications (1)

Application Number Title Priority Date Filing Date
EC2003004446A ECSP034446A (es) 2000-07-24 2003-01-23 Derivados de 4-fenil-piridon como antagonistas receptores de neuroquinina 1

Country Status (38)

Country Link
US (2) US6576762B2 (es)
EP (1) EP1305319B1 (es)
JP (1) JP4118673B2 (es)
KR (1) KR100527214B1 (es)
CN (1) CN1192032C (es)
AR (1) AR029875A1 (es)
AT (1) ATE322496T1 (es)
AU (2) AU8200501A (es)
BR (1) BR0112695A (es)
CA (1) CA2416874C (es)
CY (1) CY1106113T1 (es)
CZ (1) CZ2003528A3 (es)
DE (1) DE60118569T2 (es)
DK (1) DK1305319T3 (es)
EC (1) ECSP034446A (es)
ES (1) ES2260265T3 (es)
GT (1) GT200100148A (es)
HK (1) HK1058360A1 (es)
HR (1) HRP20030031A2 (es)
HU (1) HU229231B1 (es)
IL (2) IL153837A0 (es)
JO (1) JO2321B1 (es)
MA (1) MA26933A1 (es)
MX (1) MXPA03000367A (es)
MY (1) MY129224A (es)
NO (1) NO20030353L (es)
NZ (1) NZ523452A (es)
PA (1) PA8522801A1 (es)
PE (1) PE20020258A1 (es)
PL (1) PL366173A1 (es)
PT (1) PT1305319E (es)
RU (1) RU2276139C2 (es)
SI (1) SI1305319T1 (es)
TW (1) TWI287003B (es)
UY (1) UY26851A1 (es)
WO (1) WO2002008232A1 (es)
YU (1) YU2803A (es)
ZA (1) ZA200300219B (es)

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DK1103545T3 (da) * 1999-11-29 2004-03-15 Hoffmann La Roche 2-(3,5-bis-trifluormethyl-phenyl)-N-methyl-N-(6-morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-isobutyramide
CA2483159C (en) 2002-04-26 2010-08-10 Eli Lilly And Company Triazole derivatives as tachykinin receptor antagonists
BR0309486A (pt) 2002-04-26 2005-02-09 Lilly Co Eli Composto ou um seu sal farmaceuticamente aceitável, composição farmacêutica, e, método para o tratamento de uma condição associada com um excesso de taquicininas
AU2003300018A1 (en) * 2002-10-11 2004-05-04 Bristol-Myers Squibb Company Process for the preparation of tri-nitrogen containing heteroaryl-diamine derivatives useful as pharmaceutical agents and methods of producing pharmaceutical agents
US20060160794A1 (en) * 2003-06-12 2006-07-20 Amegadzie Albert K Tachykinin receptor antagonists
EP1643998B1 (en) 2003-07-03 2007-08-29 F. Hoffmann-La Roche Ag Dual nk1/nk3 antagonists for treating schizophrenia
TWI280239B (en) 2003-07-15 2007-05-01 Hoffmann La Roche Process for preparation of pyridine derivatives
DE602005026669D1 (de) 2004-07-06 2011-04-14 Hoffmann La Roche Herstellungsverfahren für carboxamid-pyridin-derivate als zwischenprodukte bei der synthese von nk-1-rezeptor-antagonisten
US20060030600A1 (en) * 2004-08-06 2006-02-09 Patrick Schnider Dual NK1/NK3 receptor antagonists for the treatment of schizophrenia
US20080045610A1 (en) * 2004-09-23 2008-02-21 Alexander Michalow Methods for regulating neurotransmitter systems by inducing counteradaptations
CA2580694A1 (en) * 2004-09-23 2006-03-30 Alexander Michalow Methods for regulating neurotransmitter systems by inducing counteradaptations
UA90708C2 (ru) 2005-02-25 2010-05-25 Ф. Хоффманн-Ля Рош Аг Таблетки с улучшенной дисперсностью лекарственного вещества
US8067662B2 (en) 2009-04-01 2011-11-29 Aalnex, Inc. Systems and methods for wound protection and exudate management
US7816577B2 (en) 2006-02-13 2010-10-19 Aalnex, Inc. Wound shield
WO2007137954A1 (en) 2006-05-31 2007-12-06 F. Hoffmann-La Roche Ag Aryl-4-ethynyl-isoxazole derivatives
EP2129381A1 (en) 2007-01-24 2009-12-09 Glaxo Group Limited Pharmaceutical compositions comprising 3, 5-diamin0-6- (2, 3-dichl0phenyl) -l, 2, 4-triazine or r (-) -2, 4-diamino-5- (2, 3-dichlorophenyl) -6-fluoromethyl pyrimidine and an nk1
GB0808747D0 (en) 2008-05-14 2008-06-18 Glaxo Wellcome Mfg Pte Ltd Novel compounds
US8426450B1 (en) * 2011-11-29 2013-04-23 Helsinn Healthcare Sa Substituted 4-phenyl pyridines having anti-emetic effect
JP5806420B1 (ja) 2013-11-08 2015-11-10 キッセイ薬品工業株式会社 カルボキシメチルピペリジン誘導体
TWI649307B (zh) 2014-05-07 2019-02-01 日商橘生藥品工業股份有限公司 Cyclohexylpyridine derivative
US10538491B2 (en) 2015-03-16 2020-01-21 Vanderbilt University 4,5-substituted picolinamide and picolinonitrile metabotropic glutamate receptor 2 negative allosteric modulators
WO2017112792A1 (en) 2015-12-22 2017-06-29 Takeda Pharmaceutical Company Limited Tripartite modulators of endosomal g protein-coupled receptors
US20210015834A1 (en) 2018-02-26 2021-01-21 Ospedale San Raffaele S.R.L. Nk-1 antagonists for use in the treatment of ocular pain

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IL111960A (en) 1993-12-17 1999-12-22 Merck & Co Inc Morpholines and thiomorpholines their preparation and pharmaceutical compositions containing them
SK283070B6 (sk) 1993-12-29 2003-02-04 Merck Sharp & Dohme Limited Substituované morfolínové deriváty, spôsob ich výroby, farmaceutický prostriedok s ich obsahom a ich použitie
TW385308B (en) 1994-03-04 2000-03-21 Merck & Co Inc Prodrugs of morpholine tachykinin receptor antagonists
US5972938A (en) 1997-12-01 1999-10-26 Merck & Co., Inc. Method for treating or preventing psychoimmunological disorders
JPH11322748A (ja) * 1998-03-19 1999-11-24 Takeda Chem Ind Ltd 複素環化合物、その製造法および用途
ID25818A (id) 1998-03-19 2000-11-09 Takeda Chemical Industries Ltd Senyawa-senyawa heterosiklik, produksinya dan penggunaannya
DK1394150T3 (da) * 1999-02-24 2011-03-21 Hoffmann La Roche 4-phenylpyridinderivater og deres anvendelse som NK-1-receptorantagonister
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JP4068305B2 (ja) * 1999-02-24 2008-03-26 エフ.ホフマン−ラ ロシュ アーゲー 3−フェニルピリジン誘導体、およびそのnk−1受容体拮抗薬としての用途
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DK1103545T3 (da) * 1999-11-29 2004-03-15 Hoffmann La Roche 2-(3,5-bis-trifluormethyl-phenyl)-N-methyl-N-(6-morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-isobutyramide
US6303790B1 (en) * 1999-11-29 2001-10-16 Hoffman-La Roche Inc. Process for the preparation of pyridine derivatives
KR100501608B1 (ko) * 2000-07-14 2005-07-18 에프. 호프만-라 로슈 아게 4-페닐-피리딘 유도체의 nk1 수용체의 길항성선구약물로서의 n-산화물

Also Published As

Publication number Publication date
NZ523452A (en) 2004-07-30
YU2803A (sh) 2006-01-16
CY1106113T1 (el) 2011-06-08
ZA200300219B (en) 2004-04-08
NO20030353D0 (no) 2003-01-23
US20020038030A1 (en) 2002-03-28
GT200100148A (es) 2002-05-16
DE60118569D1 (de) 2006-05-18
US6624176B2 (en) 2003-09-23
US6576762B2 (en) 2003-06-10
HK1058360A1 (en) 2004-05-14
PA8522801A1 (es) 2002-09-30
TWI287003B (en) 2007-09-21
HU229231B1 (en) 2013-09-30
PE20020258A1 (es) 2002-04-02
HUP0301272A2 (hu) 2003-08-28
MXPA03000367A (es) 2003-05-27
KR20030015898A (ko) 2003-02-25
CN1192032C (zh) 2005-03-09
UY26851A1 (es) 2002-01-31
KR100527214B1 (ko) 2005-11-08
PT1305319E (pt) 2006-08-31
AR029875A1 (es) 2003-07-16
EP1305319B1 (en) 2006-04-05
IL153837A (en) 2008-06-05
US20030130508A1 (en) 2003-07-10
HRP20030031A2 (en) 2004-02-29
CA2416874A1 (en) 2002-01-31
AU2001282005B2 (en) 2006-10-19
NO20030353L (no) 2003-01-23
IL153837A0 (en) 2003-07-31
ATE322496T1 (de) 2006-04-15
CN1444589A (zh) 2003-09-24
ES2260265T3 (es) 2006-11-01
JO2321B1 (en) 2005-09-12
DE60118569T2 (de) 2007-02-15
PL366173A1 (en) 2005-01-24
RU2276139C2 (ru) 2006-05-10
CZ2003528A3 (cs) 2003-09-17
MY129224A (en) 2007-03-30
EP1305319A1 (en) 2003-05-02
SI1305319T1 (sl) 2006-08-31
BR0112695A (pt) 2003-04-22
AU8200501A (en) 2002-02-05
MA26933A1 (fr) 2004-12-20
WO2002008232A1 (en) 2002-01-31
DK1305319T3 (da) 2006-08-14
JP4118673B2 (ja) 2008-07-16
JP2004504400A (ja) 2004-02-12
CA2416874C (en) 2011-01-18

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