PE02112007A1 - Macrocyclic compounds as inhibitors of hepatitis C virus - Google Patents

Macrocyclic compounds as inhibitors of hepatitis C virus

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Publication number
PE02112007A1
PE02112007A1 PE2006000910A PE0009102006A PE02112007A1 PE 02112007 A1 PE02112007 A1 PE 02112007A1 PE 2006000910 A PE2006000910 A PE 2006000910A PE 0009102006 A PE0009102006 A PE 0009102006A PE 02112007 A1 PE02112007 A1 PE 02112007A1
Authority
PE
Peru
Prior art keywords
c6
c1
methyl
hepatitis
diazatricyclo
Prior art date
Application number
PE2006000910A
Other languages
Spanish (es)
Inventor
Kenneth Alan Simmen
Kock Herman Augustinus De
Sandrine Marie Helene Vendeville
Abdellah Tahri
Karl Magnus Nilsson
Bengt Bertil Samuelsson
Asa Annica Kristina Rosenquist
Vladimir Ivanov
Michael Pelcman
Anna Karin Gertrud Belfrage
Per-Ola Mikael Johansson
Pierre Jean-Marie Raboisson
Lili Hu
Dominique Louis Nestor Ghislain Surleraux
Original Assignee
Medivir Ab
Tibotec Pharm Ltd
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
Family has litigation
Priority to EP05107074 priority Critical
Priority to EP05107417 priority
Priority to EP06101280 priority
Application filed by Medivir Ab, Tibotec Pharm Ltd filed Critical Medivir Ab
Publication of PE02112007A1 publication Critical patent/PE02112007A1/en
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=37067620&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=PE02112007(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04Ortho-condensed systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425Thiazoles
    • A61K31/427Thiazoles not condensed and containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47Quinolines; Isoquinolines
    • A61K31/4709Non-condensed quinolines and containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/7056Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/04Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/05Dipeptides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/21Interferons [IFN]
    • A61K38/212IFN-alpha
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/14Antivirals for RNA viruses
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D245/00Heterocyclic compounds containing rings of more than seven members having two nitrogen atoms as the only ring hetero atoms
    • C07D245/04Heterocyclic compounds containing rings of more than seven members having two nitrogen atoms as the only ring hetero atoms condensed with carbocyclic rings or ring systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D277/00Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
    • C07D277/56Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • 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
    • C07D401/14Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic 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
    • C07D417/02Heterocyclic 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
    • C07D417/04Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic 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
    • C07D417/14Heterocyclic 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 three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06Dipeptides
    • C07K5/06139Dipeptides with the first amino acid being heterocyclic
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
    • Y02A50/38Medical treatment of vector-borne diseases characterised by the agent
    • Y02A50/381Medical treatment of vector-borne diseases characterised by the agent the vector-borne disease being caused by a virus
    • Y02A50/384Medical treatment of vector-borne diseases characterised by the agent the vector-borne disease being caused by a virus of the genus Flavivirus
    • Y02A50/385Medical treatment of vector-borne diseases characterised by the agent the vector-borne disease being caused by a virus of the genus Flavivirus the disease being Dengue
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
    • Y02A50/38Medical treatment of vector-borne diseases characterised by the agent
    • Y02A50/381Medical treatment of vector-borne diseases characterised by the agent the vector-borne disease being caused by a virus
    • Y02A50/384Medical treatment of vector-borne diseases characterised by the agent the vector-borne disease being caused by a virus of the genus Flavivirus
    • Y02A50/387Medical treatment of vector-borne diseases characterised by the agent the vector-borne disease being caused by a virus of the genus Flavivirus the disease being Yellow fever, i.e. Ochropyra
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
    • Y02A50/38Medical treatment of vector-borne diseases characterised by the agent
    • Y02A50/381Medical treatment of vector-borne diseases characterised by the agent the vector-borne disease being caused by a virus
    • Y02A50/384Medical treatment of vector-borne diseases characterised by the agent the vector-borne disease being caused by a virus of the genus Flavivirus
    • Y02A50/389Medical treatment of vector-borne diseases characterised by the agent the vector-borne disease being caused by a virus of the genus Flavivirus the disease being Japanese encephalitis
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
    • Y02A50/38Medical treatment of vector-borne diseases characterised by the agent
    • Y02A50/381Medical treatment of vector-borne diseases characterised by the agent the vector-borne disease being caused by a virus
    • Y02A50/384Medical treatment of vector-borne diseases characterised by the agent the vector-borne disease being caused by a virus of the genus Flavivirus
    • Y02A50/393Medical treatment of vector-borne diseases characterised by the agent the vector-borne disease being caused by a virus of the genus Flavivirus the disease being West Nile fever

Abstract

SE REFIERE A COMPUESTOS MACROCICLICOS DE FORMULA (I) DONDE LA LINEA DE PUNTOS ES UN DOBLE ENLACE OPCIONAL; CONCERNS macrocyclic compounds of formula (I) wherein the dotted line is a double bond OPTIONAL; X ES N, CH Y CUANDO X POSEE UN DOBLE ENLACE ES C; X is N, CH and where X has a double ES C; R1 ES OR7 O -NH-SO2R8; R1 is OR7 or -NH-SO2R8; R2 ES HY CUANDO X ES CO CH, R2 TAMBIEN PUEDE SER ALQUILO(C1-C6); R2 IS HY when X is CO CH, R2 may also be (C1-C6); R3 ES H, ALQUILO(C1-C6), CICLOALQUILO(C3-C7) O ALCOXI(C1-C6)-ALQUILO(C1-C6); R3 is H, alkyl (C1-C6), cycloalkyl (C3-C7) alkyl or (C1-C6) cycloalkyl- (C1-C6); R4 ES ARILO O HET, DONDE HET ES HETEROCICLICO DE 5 O 6 MIEMBROS DE 1 A 4 HETEROATOMOS SELECCIONADOS DE N, OUS, OPCIONALMENTE SUSTITUIDO; R4 is aryl or HET, wherein Het is a 5- or 6-membered 1 to 4 heteroatoms selected from N, OUS, optionally substituted; R5 ES HALO, ALQUILO(C1-C6), HIDROXI, ALCOXI(C1-C6), ENTRE OTROS; R5 is halo, (C1-C6), hydroxy, (C1-C6), among others; R6 ES ALCOXI(C1-C6) O DIMETILAMINO; R6 is alkoxy (C1-C6) or dimethylamino; n ES DE 3 A 6. SON PREFERIDOS: ACIDO 17-[7-METOXI-8-METIL-2-(TIAZOL-2-IL)QUINOLIN-4-ILOXI]-13-METIL-2,14-DIOXO-3,13-DIAZATRICICLO[13.3.0.0(4,6)]OCTADEC-7-EN-4-CARBOXILICO, N-[17-[7-METOXI-8-METIL-2-(TIAZOL-2-IL)QUINOLIN-4-ILOXI]-13-METIL-2,14-DIOXO-3,13-DIAZATRICICLO[13.3.0.0(4,6)]OCTADEC-7-EN-4-CARBONIL]-(CICLOPROPIL)SULFONAMIDA, ENTRE OTROS. n is 3 to 6. Preferred: 17- [7-methoxy-8-methyl-2- (thiazol-2-yl) quinolin-4-yloxy] -13-methyl-2,14-DIOXO-3, 13-diazatricyclo [13.3.0.0 (4,6)] octadec-7-en-4-carboxylic acid, N- [17- [7-methoxy-8-methyl-2- (thiazol-2yl) quinolin-4- yloxy] -13-methyl-2,14-Dioxo-3,13-diazatricyclo [13.3.0.0 (4,6)] octadec-7-en-4-carbonyl] - (cyclopropyl) sulfonamide, among others. SE REFIERE TAMBIEN A UNA COMPOSICION FARMACEUTICA QUE ADEMAS PUEDE COMPRENDER OTRO AGENTE ACTIVO TAL COMO RITONAVIR YA UN PROCEDIMIENTO DE PREPARACION. SE also relates to a pharmaceutical composition which also may comprise another active agent AS ritonavir and method of preparation. ESTOS COMPUESTOS TIENEN ACTIVIDAD INHIBITORIA SOBRE LA REPLICACION DEL VIRUS DE LA HEPATITIS C SIENDO UTILES EN EL TRATAMIENTO DE LA HEPATITIS C These compounds have INHIBITORY ACTIVITY ON THE replication Hepatitis C virus REMAIN IN THE TREATMENT OF USEFUL HEPATITIS C
PE2006000910A 2005-07-29 2006-07-26 Macrocyclic compounds as inhibitors of hepatitis C virus PE02112007A1 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP05107074 2005-07-29
EP05107417 2005-08-11
EP06101280 2006-02-03

Publications (1)

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PE02112007A1 true PE02112007A1 (en) 2007-05-12

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ID=37067620

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PE2006000910A PE02112007A1 (en) 2005-07-29 2006-07-26 Macrocyclic compounds as inhibitors of hepatitis C virus

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US (9) US8148399B2 (en)
EP (3) EP2937339A1 (en)
JP (1) JP4797067B2 (en)
KR (1) KR101059419B1 (en)
CN (3) CN101228169B (en)
AP (1) AP2406A (en)
AR (1) AR055359A1 (en)
AT (1) AT494288T (en)
AU (1) AU2006274865B2 (en)
BR (1) BRPI0614654B1 (en)
CA (1) CA2616580C (en)
CR (1) CR9783A (en)
CY (2) CY1112006T1 (en)
DE (1) DE602006019439D1 (en)
DK (2) DK2322516T3 (en)
EA (1) EA015131B1 (en)
EC (1) ECSP088150A (en)
ES (1) ES2555230T3 (en)
GT (1) GT200600339A (en)
HK (2) HK1116771A1 (en)
HN (1) HN2008000134A (en)
HR (2) HRP20110237T1 (en)
HU (2) HUE027156T2 (en)
IL (2) IL188227A (en)
LU (1) LU92568I2 (en)
ME (2) ME02415B (en)
MY (1) MY144217A (en)
NO (1) NO342393B1 (en)
NZ (1) NZ564550A (en)
PE (1) PE02112007A1 (en)
PL (1) PL1912999T3 (en)
PT (2) PT1912999E (en)
RS (2) RS54473B1 (en)
SG (1) SG163617A1 (en)
SI (2) SI1912999T1 (en)
SV (1) SV2008002642A (en)
TW (1) TWI358411B (en)
UY (1) UY29703A1 (en)
WO (1) WO2007014926A1 (en)
ZA (1) ZA200800857B (en)

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