AR037863A1 - DERIVATIVES OF TETRAHYDROCARBAZOL AS LIGANDS FOR RECEPTORS (GPCR) COUPLED THROUGH PROTEIN G - Google Patents

DERIVATIVES OF TETRAHYDROCARBAZOL AS LIGANDS FOR RECEPTORS (GPCR) COUPLED THROUGH PROTEIN G

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Publication number
AR037863A1
AR037863A1 ARP020104893A ARP020104893A AR037863A1 AR 037863 A1 AR037863 A1 AR 037863A1 AR P020104893 A ARP020104893 A AR P020104893A AR P020104893 A ARP020104893 A AR P020104893A AR 037863 A1 AR037863 A1 AR 037863A1
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AR
Argentina
Prior art keywords
radical
group
atom
aryl
substituted
Prior art date
Application number
ARP020104893A
Other languages
Spanish (es)
Inventor
Koppitz Marcus Dr
Muhn Hans-Peter Dr
Shaw Ken Dr
Hess-Stumpp Holger Dr
Paulini Klaus Dr
Original Assignee
Zentaris 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.)
Filing date
Publication date
Priority claimed from DE10164564A external-priority patent/DE10164564B4/en
Application filed by Zentaris Ag filed Critical Zentaris Ag
Publication of AR037863A1 publication Critical patent/AR037863A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
    • C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/16—Masculine contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/18—Feminine contraceptives
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/56—Ring systems containing three or more rings
    • C07D209/80—[b, c]- or [b, d]-condensed
    • C07D209/82—Carbazoles; Hydrogenated carbazoles
    • C07D209/86—Carbazoles; Hydrogenated carbazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the ring system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/56—Ring systems containing three or more rings
    • C07D209/80—[b, c]- or [b, d]-condensed
    • C07D209/82—Carbazoles; Hydrogenated carbazoles
    • C07D209/88—Carbazoles; Hydrogenated carbazoles 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 carbon atoms of the ring system
    • 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
    • C07D401/02—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 two hetero rings
    • C07D401/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Gynecology & Obstetrics (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pregnancy & Childbirth (AREA)
  • Diabetes (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Indole Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Derivados de tetrahidrocarbazol que actúan como ligandos para receptores (GPCR) acoplados a través de la proteína G, especialmente como antagonistas de la hormona liberadora de la gonadotropina (GnRH). Además, una composición farmacéutica que contiene estos derivados de tetrahidrocarbazol, así como un método para preparar los nuevos derivados de tetrahidrocarbazol. La presente se refiere además a la administración de derivados de tetrahidrocarbazol para el tratamiento de estados patológicos mediados por el GPCR, sobre todo para inhibir la GnRH en mamíferos, especialmente en humanos que requieren de una administración semejante, así como al uso de derivados de tetrahidrocarbazol para preparar un agente farmacéutico para el tratamiento de estados patológicos mediados por el GPCR, en especial para inhibir la GnRH. Reivindicación 1: Compuesto caracterizado porque responde a la fórmula general (1) donde el radical R1 es un átomo de H, un radical alquenilo C2-6 o un radical alquilo C1-6, y puede estar opcionalmente sustituido por un radical arilo, un radical hetarilo o el grupo -COOR11, donde el radical arilo o hetarilo puede ser sustituido por hasta tres sustituyentes seleccionados independientemente entre sí del grupo formado por -NO2, -CH3, -CF3, -OCH3 -OCF3 y átomos de halógeno, y el radical R11 es un átomo de H, un radical alquilo C1-12, un radical aralquilo C1-12, un radical arilo, un radical hetarilo o el grupo -COCH3 y opcionalmente puede ser sustituido por un sustituyente seleccionado del grupo -CONH2, -COCH3, -COOCH3, -SO2CH3 y radicales arilo; los radicales R2, R3, R4 y R5 son, independientemente entre sí, un átomo de H, un átomo de halógeno, el grupo COOH, -CONH2, -CF3, -OCF3, -NO2, -CN, un radical alquilo C1-6, un radical alquenilo C1-6, un radical alcoxi C1-6, un radical aralquilo C1-12, un radical arilo o un radical hetarilo; el radical R6 es el grupo -CONR8R9, -COOR8, -CH2NR8R9, -CH2R8, -CH2OR8 o un radical alquenilo C1-12, que puede estar sustituido por los radicales R8 y R9, donde los radicales R8 y R9 son, independientemente entre sí, un átomo de H, un radical alquilo C1-12, un radical aralquilo C1-12, un radical hetaralquilo C1-12, un radical arilo o un radical hetarilo, los cuales pueden estar sustituidos por uno o varios sustituyentes seleccionados del grupo integrado por -OH, -NH2, -CONHR10, COOR10, -NH-C-(=NH)-NH2 y átomos de halógeno, donde el radical R10 es un átomo de H, un radical alquilo C1-12, un radical aralquilo C1-12, un radical arilo o un radical hetarilo y que puede estar sustituido por el grupo -CON(R11)2, o donde los radicales R8 y R9 pueden formar juntos una estructura cíclica que está compuesta exclusivamente por átomos de carbono o por una mezcla de átomos de carbono y heteroátomos; el radical R7 es un átomo de H, un radical alquilo C1-12, un radical alquenilo C1-12, un radical aralquilo C1-12, un radical arilo o un radical hetarilo, el grupo NR12R13, -NHCOR14, NHCONHR14, NHCOOR14 o NHSO2R14 y opcionalmente puede estar sustituido por uno o varios sustituyentes seleccionados del grupo integrado por -OH, -NH2, -CONH2, -COOH y átomos de halógeno, los radicales R12 y R13 son, independientemente entre sí, un átomo de H, un radical alquenilo C2-6 o un radical alquilo C1-12 y pueden estar opcionalmente sustituidos por uno o varios radicales arilo o hetarilo, los cuales a su vez, pueden estar sustituidos por hasta tres sustituyentes seleccionados independientemente entre sí del grupo formado por -NO2, -CH3, -CF3, -OCH3, -OCF3 y átomos de halógeno, y el radical R14 es un átomo de H, un radical alquilo C1-12, un radical alquenilo C1-12, un radical aralquilo C1-12, un radical arilo o un radical hetarilo, que puede estar opcionalmente sustituido por uno o varios sustituyentes seleccionados del grupo integrado por -NO2, -CH3, -OR11, -CF3, -OCF3, -OH, -N(R11)2, -OCOR11, -COOH, -CONH2, -NHCONHR11, -NHCOOR11 y átomos de halógeno; y los radicales Ra, Rb, Rc, Rd, Re y Rf son, independientemente entre sí, un átomo de H, un átomo de halógeno, el grupo -COOH, -CONH2, -CF3, -OCF3, -NO2, -CN, un radical alquilo C1-6, un radical alcoxi C1-6, un radical arilo o un radical hetarilo; con la condición de que el compuesto de la fórmula general (1) no se seleccione del grupo integrado por ácido 3-amino-1,2,3,4-tetrahidrocarbazol-3-carboxílico, ácido 3-amino-6-metoxi-1,2,3,4-tetrahidrocarbazol-3-carboxílico, ácido 3-amino-6-benciloxi-1,2,3,4-tetrahidrocarbazol-3-carboxílico, ácido 3-acetamido-1,2,3,4-tetrahidrocarbazol-3-carboxílico, metil-3-acetamido-1,2,3,4-tetrahidrocarbazol-3-carboxilato, (-)-metil-3-acetamido-1,2,3,4-tetrahidrocarbazol-3-carboxilato o ácido 3-ter-butoxicarbonil-amino-1,2,3,4-tetrahidrocarbazol-3-carboxílico.Tetrahydrocarbazole derivatives that act as ligands for receptors (GPCRs) coupled through the G protein, especially as gonadotropin-releasing hormone (GnRH) antagonists. In addition, a pharmaceutical composition containing these tetrahydrocarbazole derivatives, as well as a method for preparing the new tetrahydrocarbazole derivatives. This also relates to the administration of tetrahydrocarbazole derivatives for the treatment of pathological conditions mediated by GPCR, especially to inhibit GnRH in mammals, especially in humans that require similar administration, as well as the use of tetrahydrocarbazole derivatives. to prepare a pharmaceutical agent for the treatment of pathological conditions mediated by GPCR, especially to inhibit GnRH. Claim 1: Compound characterized in that it responds to the general formula (1) wherein the radical R1 is an H atom, a C2-6 alkenyl radical or a C1-6 alkyl radical, and may be optionally substituted by an aryl radical, a radical hetaryl or the group -COOR11, where the aryl or hetaryl radical can be substituted by up to three substituents independently selected from each other from the group consisting of -NO2, -CH3, -CF3, -OCH3 -OCF3 and halogen atoms, and the radical R11 it is an H atom, a C1-12 alkyl radical, a C1-12 aralkyl radical, an aryl radical, a heteroaryl radical or the group -COCH3 and can optionally be substituted by a substituent selected from the group -CONH2, -COCH3, - COOCH3, -SO2CH3 and aryl radicals; the radicals R2, R3, R4 and R5 are, independently of each other, an H atom, a halogen atom, the COOH group, -CONH2, -CF3, -OCF3, -NO2, -CN, a C1-6 alkyl radical , a C1-6 alkenyl radical, a C1-6 alkoxy radical, a C1-12 aralkyl radical, an aryl radical or a heteroaryl radical; the radical R6 is the group -CONR8R9, -COOR8, -CH2NR8R9, -CH2R8, -CH2OR8 or a C1-12 alkenyl radical, which may be substituted by radicals R8 and R9, where radicals R8 and R9 are, independently of each other , an H atom, a C1-12 alkyl radical, a C1-12 aralkyl radical, a C1-12 hetaralkyl radical, an aryl radical or a heteroaryl radical, which may be substituted by one or more substituents selected from the group consisting of -OH, -NH2, -CONHR10, COOR10, -NH-C - (= NH) -NH2 and halogen atoms, where the R10 radical is an H atom, a C1-12 alkyl radical, a C1-12 aralkyl radical , an aryl radical or a heteroaryl radical and which may be substituted by the group -CON (R11) 2, or where the radicals R8 and R9 can together form a cyclic structure that is composed exclusively of carbon atoms or a mixture of atoms carbon and heteroatoms; the radical R7 is an atom of H, a C1-12 alkyl radical, a C1-12 alkenyl radical, a C1-12 aralkyl radical, an aryl radical or a heteroaryl radical, the group NR12R13, -NHCOR14, NHCONHR14, NHCOOR14 or NHSO2R14 and optionally it may be substituted by one or more substituents selected from the group consisting of -OH, -NH2, -CONH2, -COOH and halogen atoms, the radicals R12 and R13 are, independently of each other, an H atom, an alkenyl radical C2-6 or a C1-12 alkyl radical and may be optionally substituted by one or more aryl or hetaryl radicals, which in turn may be substituted by up to three substituents independently selected from the group consisting of -NO2, -CH3 , -CF3, -OCH3, -OCF3 and halogen atoms, and the radical R14 is an H atom, a C1-12 alkyl radical, a C1-12 alkenyl radical, a C1-12 aralkyl radical, an aryl radical or a heteroaryl radical, which may be optionally substituted by one or more substitutes Ituents selected from the group consisting of -NO2, -CH3, -OR11, -CF3, -OCF3, -OH, -N (R11) 2, -OCOR11, -COOH, -CONH2, -NHCONHR11, -NHCOOR11 and halogen atoms; and the radicals Ra, Rb, Rc, Rd, Re and Rf are, independently from each other, an H atom, a halogen atom, the group -COOH, -CONH2, -CF3, -OCF3, -NO2, -CN, a C1-6 alkyl radical, a C1-6 alkoxy radical, an aryl radical or a heteroaryl radical; with the proviso that the compound of the general formula (1) is not selected from the group consisting of 3-amino-1,2,3,4-tetrahydrocarbazol-3-carboxylic acid, 3-amino-6-methoxy-1 acid , 2,3,4-tetrahydrocarbazol-3-carboxylic acid, 3-amino-6-benzyloxy-1,2,3,4-tetrahydrocarbazol-3-carboxylic acid, 3-acetamido-1,2,3,4-tetrahydrocarbazole -3-carboxylic, methyl-3-acetamido-1,2,3,4-tetrahydrocarbazol-3-carboxylate, (-) - methyl-3-acetamido-1,2,3,4-tetrahydrocarbazol-3-carboxylate or acid 3-tert-butoxycarbonyl-amino-1,2,3,4-tetrahydrocarbazol-3-carboxylic acid.

ARP020104893A 2001-12-14 2002-12-17 DERIVATIVES OF TETRAHYDROCARBAZOL AS LIGANDS FOR RECEPTORS (GPCR) COUPLED THROUGH PROTEIN G AR037863A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10164564A DE10164564B4 (en) 2001-12-14 2001-12-14 Tetrahydrocarbazole derivatives as ligands for G-protein coupled receptors (GPCR)
US34187801P 2001-12-21 2001-12-21

Publications (1)

Publication Number Publication Date
AR037863A1 true AR037863A1 (en) 2004-12-09

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ARP020104893A AR037863A1 (en) 2001-12-14 2002-12-17 DERIVATIVES OF TETRAHYDROCARBAZOL AS LIGANDS FOR RECEPTORS (GPCR) COUPLED THROUGH PROTEIN G

Country Status (17)

Country Link
EP (1) EP1453803A2 (en)
JP (1) JP2005518375A (en)
CN (1) CN100500654C (en)
AR (1) AR037863A1 (en)
AU (1) AU2002361430B2 (en)
BR (1) BR0214958A (en)
CA (1) CA2468880A1 (en)
HR (1) HRP20040609A2 (en)
HU (1) HUP0500014A3 (en)
IL (2) IL161626A0 (en)
MX (1) MXPA04005768A (en)
NO (1) NO326692B1 (en)
NZ (1) NZ533430A (en)
PL (1) PL373400A1 (en)
RU (1) RU2319692C2 (en)
TW (1) TWI246423B (en)
WO (1) WO2003051837A2 (en)

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SI1638551T1 (en) * 2003-05-19 2012-04-30 Irm Llc Immunosuppressant compounds and compositions
ES2314446T3 (en) * 2003-06-10 2009-03-16 Smithkline Beecham Corporation DERIVATIVES OF TETRAHYDROCARBAZOL AND ITS PHARMACEUTICAL USE.
US20060074124A1 (en) 2003-09-12 2006-04-06 Andrew Napper Methods of treating a disorder
US20050209300A1 (en) * 2003-09-12 2005-09-22 Andrew Napper Methods of treating a disorder
DE102004033902A1 (en) 2004-07-14 2006-02-16 Zentaris Gmbh New tetrahydrocarbazole compounds are neurokinin-1 receptor antagonists useful to treat or prevent e.g. pubertas praecox, hirsutism, polycystic ovary syndrome, hormone dependent neoplastic diseases and Alzheimer's disease
PT1833791E (en) * 2004-12-27 2011-10-19 Actelion Pharmaceuticals Ltd 2,3,4,9-tetrahydro-1h-carbazole derivatives as crth2 receptor antagonists
BRPI0611705A2 (en) * 2005-06-24 2016-11-16 Lilly Co Eli compound or a pharmaceutically acceptable salt thereof, pharmaceutical composition, and use of compound
KR101411820B1 (en) * 2006-08-07 2014-06-24 액테리온 파마슈티칼 리미티드 (3-amino-1,2,3,4-tetrahydro-9h-carbazol-9-yl)-acetic acid derivatives
EP1967202A1 (en) * 2007-03-05 2008-09-10 AEterna Zentaris GmbH Use of LHRH Antagonists for the Treatment of Lower Urinary Tract Symptoms, in particular Overactive Bladder and/or Detrusor Overactivity
EP1988098A1 (en) * 2007-04-27 2008-11-05 AEterna Zentaris GmbH Novel Tetrahydrocarbazole Derivatives as Ligands of G-protein Coupled Receptors
EP2095818A1 (en) 2008-02-29 2009-09-02 AEterna Zentaris GmbH Use of LHRH antagonists at non-castrating doses
BR112012024114B1 (en) 2010-03-22 2021-02-09 Idorsia Pharmaceuticals Ltd COMPOUNDS DERIVED FROM 3- (HETEROARYLAMINE) -1,2,3,4-TETRAHYDRO-9H-CARBAZOLE, USE OF THE SAME, AND, PHARMACEUTICAL COMPOSITION
CN103459389B (en) 2011-04-14 2016-03-30 埃科特莱茵药品有限公司 7-(heteroaryl-amino)-6,7,8,9-tetrahydropyridine is [1,2-a] ethychlozate derivative and its purposes as prostaglandin D 2 receptor conditioning agent also
PE20161177A1 (en) 2014-03-17 2016-11-18 Actelion Pharmaceuticals Ltd DERIVATIVES OF AZAINDOL ACETIC ACID AND THEIR USE AS MODULATORS OF THE PROSTAGLANDIN D2 RECEPTOR
US9850241B2 (en) 2014-03-18 2017-12-26 Idorsia Pharmaceuticals Ltd Azaindole acetic acid derivatives and their use as prostaglandin D2 receptor modulators
TWI711616B (en) 2015-09-15 2020-12-01 瑞士商愛杜西亞製藥有限公司 Crystalline forms

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EP0239306B1 (en) * 1986-03-27 1993-06-02 Merck Frosst Canada Inc. Tetrahydrocarbazole esters
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EP0986385A4 (en) * 1997-06-05 2001-05-16 Merck & Co Inc Antagonists of gonadotropin releasing hormone

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JP2005518375A (en) 2005-06-23
CA2468880A1 (en) 2003-06-26
RU2004121776A (en) 2005-05-10
WO2003051837A2 (en) 2003-06-26
AU2002361430B2 (en) 2007-09-13
IL161626A0 (en) 2004-09-27
CN1599720A (en) 2005-03-23
MXPA04005768A (en) 2004-09-10
HUP0500014A2 (en) 2005-04-28
RU2319692C2 (en) 2008-03-20
TW200305405A (en) 2003-11-01
WO2003051837A8 (en) 2004-05-06
NO20042198L (en) 2004-07-09
WO2003051837A3 (en) 2004-02-26
AU2002361430A1 (en) 2003-06-30
BR0214958A (en) 2004-12-28
HRP20040609A2 (en) 2005-06-30
CN100500654C (en) 2009-06-17
NZ533430A (en) 2005-12-23
EP1453803A2 (en) 2004-09-08
NO326692B1 (en) 2009-02-02
TWI246423B (en) 2006-01-01
PL373400A1 (en) 2005-08-22
HUP0500014A3 (en) 2010-06-28
IL192991A0 (en) 2011-08-01

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