AR058002A1 - Hidroxamatos como inhibidores de la histona deacetilasa y formulaciones farmaceuticas que los contienen - Google Patents

Hidroxamatos como inhibidores de la histona deacetilasa y formulaciones farmaceuticas que los contienen

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Publication number
AR058002A1
AR058002A1 ARP060100977A ARP060100977A AR058002A1 AR 058002 A1 AR058002 A1 AR 058002A1 AR P060100977 A ARP060100977 A AR P060100977A AR P060100977 A ARP060100977 A AR P060100977A AR 058002 A1 AR058002 A1 AR 058002A1
Authority
AR
Argentina
Prior art keywords
phenyl
group
alkyl
independently
pyrrolidino
Prior art date
Application number
ARP060100977A
Other languages
English (en)
Inventor
Cristina Rossi
Marina Porcelloni
Andrea Piero D
Daniela Fattori
Elena Marastoni
Original Assignee
Menarini Internat Operation Lu
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Filing date
Publication date
Application filed by Menarini Internat Operation Lu filed Critical Menarini Internat Operation Lu
Publication of AR058002A1 publication Critical patent/AR058002A1/es

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    • 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
    • C07D405/02—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 two hetero rings
    • C07D405/06—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 two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • 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
    • A61P37/02—Immunomodulators
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/92—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with a hetero atom directly attached to the ring nitrogen atom
    • C07D211/96—Sulfur atom
    • 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
    • C07D401/06—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 carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • 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
    • C07D413/06—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 carbon chain containing only aliphatic carbon atoms
    • 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
    • C07D417/06—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 carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/11—Compounds covalently bound to a solid support

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Immunology (AREA)
  • Obesity (AREA)
  • Oncology (AREA)
  • Rheumatology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pain & Pain Management (AREA)
  • Pulmonology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Hydrogenated Pyridines (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Reivindicacion 1: Es particularmente objeto de la presente, un compuesto que tiene una formula general (1) donde v = 0, 1, 2; B es una union, o bien es seleccionado en el grupo -O-, -NR5-, -CO-, -NR5-CO-, -O-CO-, -SO2-, -NR5-SO2-, o bien representa una de las estructuras de formula (2) o (3), donde n = 0, 1, 2; donde R5 es un H o alquilo C1-3; R1 representa un H, o bien es seleccionado en el grupo alquilo C1-3, acilo C1-3 o un acilo derivado de uno de los siguientes ácidos: benzoico, fenil acético, benzotiofen-carboxílico, indol-carboxílico; R2 representa un H o alquilo C1-3; o bien R1 y R2 conjuntamente representan con el átomo de N, un heterociclo de 5 o 6 miembros seleccionado entre pirrolidino, piperidino, piperazino, morfolino, tiomorfolino; R3 representa H o bien es seleccionado en el grupo alquilo C1-6, alquilona C1-6-W, o bien W es seleccionado entre -OR5, -SR5, -CONR7R8, -NR7R8, -OCOR6-NR5COR6, guanidina, y R7 y R8 independientemente representan un grupo H o un alquilo C1-3 o bien R7 y R8 conjuntamente al átomo de N un heterociclo de 5 o 6 miembros seleccionado entre pirrolidino, piperidino, piperazino, morfolino, tiomorfolino; y R6 es seleccionado en el grupo H, alquilo c1-3, Ar1 o bien Ar1 es un grupo aromático seleccionado entre fenilo, naftilo, piridino, quinolino, indol, benzofurano, benzotiofeno y puede ser eventualmente sustituido con hasta 3 grupos independientemente seleccionados entre alquilo C1-3, OR9, SR9, NR9R10, N(R9)COR10, NO2, CN, F, Cl, Br, - CF3, COOR9, CONR9R10, CH2NR9R10, N(R9)SO2R10, CH2OR9, SOH, CH2SO3H, donde R9 es un grupo seleccionado entre H, alquilo C1-3, -(CH2)q-NR10R11, pirrolidino; R10 y R11 son independientemente un grupo seleccionado entre H y alquilo C1-3, q puede asumir los valores 2 o 3; R4 es un grupo seleccionado entre H y alquilo C1-3; o bien R4 y R3 conjuntamente con el átomo de N representan un heterociclo seleccionado entre pirrolidino o piperidino; L1 es seleccionado en el grupo alquilideno del tipo -(CH2)m- , eventualmente sustituido sobre cada C con uno o dos grupos metilo, y donde m puede asumir los valores 1, 2, 3; L2 indica una union o bien un grupo seleccionado entre -(CH2)p-, -(CH2)p-CH=CH-, -(CH2)p-T-(CH2)z-, -(CH2)p-CO-, -(CH2)p-CH=CH-CO-, -CO- T-(CH2)z-, -(CH2)p-T-CO-, cada grupo eventualmente sustituido sobre C con 1 o 2 grupos metilos y en el cual p y z independientemente pueden asumir los valores 0, 1, 2, 3 o 4 y T es seleccionado entre -O-, -S-, -NR5-; Ar representa un grupo derivado de los siguientes sistemas aromáticos: fenilo, piridilo, furilo, pirimidilo, pirazilo, piperazilo, triazolilo, tetrazolilo, bifenilo, imidazolilo, naftilo, quinolilo, isoquinolilo, difenil-metilo, benzofurilo, dihidrobenzofurilo, benzotienilo, indolilo, benzotiazolilo, benzoxazolilo, benzoisoxazolilo, oxazolil-fenilo, tiodiazolil-fenilo, piridil-fenilo, pirazolil-fenilo, tiazolil-fenilo, furil-fenilo, tienil-fenilo, benciloxi-fenilo, tetrazolil-fenilo, fenil-oxazolilo, fenil-pirazolilo, fenil-tiazolilo, fenil-tiadiazolilo, fenil-isotiazolilo, fenil-oxadiazolilo, fenil-isoxazolilo, fenil-imidazolilo, fenil-triazolilo, fenil-furilo, fenil-tiofenilo, fenil-pirrolilo, fenil-pirrolidilo, indanilo, fluorenilo, benzopiranilo, dihidrobenzopiranilo, benzodioxolilo, fenoxi-fenilo, benzoxazinilo, dihidrobenzoxazinilo donde cada grupo puede ser eventualmente sustituido con hasta tres grupos independientemente seleccionados entre alquilo C1-3, OR9, SR9, NR9R10, N(R9)COR10, NO2, CN, F, Cl, Br, -CF3, SCF3, COOR9, CONR9R10, -(CH2)q-NR9R10, N(R9)SO2R10, CH2OR9, SOH, CH2SO3H, donde R9 es un grupo seleccionado entre H, alquilo C1-4, -(CH2)q-NR10R11, pirrolidino; R10 y R11 son independientemente un grupo seleccionado entre H y alquilo C1-3, q puede asumir los valores 1, 2 o 3; o bien Ar-L2-B- conjuntamente pueden ser seleccionados del grupo constituido por las formulas (4), donde el grupo R12 representa un H, alquilo C1-3 o acilo C1-3; el grupo Ar2 es un aromático seleccionado entre bencilo o un grupo acilo derivado de los ácidos benzoico, fenilacético o benzotiofencarboxílico, la parte aromática puede ser sustituida hasta 3 grupos independientemente seleccionados entre alquilo C1-3, OR9, SR9, NR9R10, N(R9)COR10, NO2, CN, F, Cl, Br, -CF3, -SCF3, COOR9, CONR9R10, -(CH2)q-NR9R10, N(R9)SO2R10, CH2OR9, SOH, CH2SO3H, donde R9 es un grupo seleccionado entre H, alquilo C1-4, -(CH2)q-NR10R11, pirrolidino; R10 y R11 son independientemente un grupo seleccionado entre H y alquilo C1-3, q puede asumir los valores 1, 2 o 3; los relativos prodrogas de formula general (5) y (6) donde Rx puede ser Ac, COEt, CO-nPr, CO-iPr, CO-tBu, benzoilo, pNO2benzoilo, CH3, Et, nPr, iPr, tBu, bencilo, tetrahidropiranilo; Ry y Rz independientemente entre ellos indican un grupo H o bien un alquilo C1-3 con la exclusion de los productos donde se encuentre: B seleccionado entre -NR5-CO- o bien -NR5-SO2- y contemporáneamente L3 seleccionado entre - (CH2)p-CO- o bien -(CH2)p-CH=CH-CO-; los posibles isomeros opticos, como enantiomeros y/o diastereoisomeros, sus mezclas, ya sea como racematos, que como las distintas relaciones entre ellos, y su sales de ácidos inorgánicos y orgánicos.
ARP060100977A 2005-03-15 2006-03-14 Hidroxamatos como inhibidores de la histona deacetilasa y formulaciones farmaceuticas que los contienen AR058002A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IT000041A ITFI20050041A1 (it) 2005-03-15 2005-03-15 Idrossammati come inibitori dell'istone deacelitasi, loro preparazione e formulazioni farmaceutiche che li contengono
IT000239A ITFI20050239A1 (it) 2005-03-15 2005-11-21 Idrossammati come inibitori dell'istone deacetilasi e formulazioni farmaceutiche che li contegono

Publications (1)

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AR058002A1 true AR058002A1 (es) 2008-01-23

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ARP060100977A AR058002A1 (es) 2005-03-15 2006-03-14 Hidroxamatos como inhibidores de la histona deacetilasa y formulaciones farmaceuticas que los contienen

Country Status (22)

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US (1) US20080207694A1 (es)
EP (1) EP1868997A1 (es)
JP (1) JP2008533091A (es)
KR (1) KR20070112240A (es)
CN (1) CN101155780A (es)
AP (1) AP2007004188A0 (es)
AR (1) AR058002A1 (es)
AU (1) AU2006224624A1 (es)
BR (1) BRPI0606290A2 (es)
CA (1) CA2600528A1 (es)
CO (1) CO6321134A2 (es)
CR (1) CR9431A (es)
EA (1) EA012909B1 (es)
IL (1) IL185882A0 (es)
IT (2) ITFI20050041A1 (es)
MA (1) MA29389B1 (es)
MX (1) MX2007011072A (es)
NO (1) NO20075281L (es)
SA (1) SA06270135B1 (es)
TW (1) TW200724529A (es)
WO (1) WO2006097460A1 (es)
ZA (1) ZA200708749B (es)

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KR20080054417A (ko) * 2005-09-27 2008-06-17 노파르티스 아게 카르복시아민 화합물 및 ｈｄａｃ 의존성 질환의 치료에있어서의 그의 용도
GB0523040D0 (en) * 2005-11-11 2005-12-21 Cyclacel Ltd Combination
US20100261710A1 (en) * 2007-08-21 2010-10-14 Arqule, Inc. HDAC Inhibitors
CN102775368B (zh) * 2011-05-10 2016-08-17 上海驺虞医药科技有限公司 一类噻唑类化合物及其制备方法和用途
KR20180098593A (ko) * 2015-12-22 2018-09-04 칸세라 아베 포유류의 히스톤 탈아세틸화효소 활성에 대한 저해제로서 유용한 바이사이클릭 하이드록사믹산
KR102264012B1 (ko) * 2015-12-31 2021-06-10 히트젠 주식회사 술폰아마이드 유도체 및 그 제조방법과 응용
CN112325620B (zh) * 2020-11-13 2022-04-19 南阳中联水泥有限公司 一种水泥生产高效烘干设备
CN112516142B (zh) * 2020-12-11 2021-10-15 北京华氏精恒医药科技有限公司 一种具有hdac抑制活性的药物组合物、制备方法及其用途
WO2023003468A1 (en) * 2021-07-23 2023-01-26 Rijksuniversiteit Groningen Novel inhibitors of histone deacetylase (hdac), and methods, compositions and uses related thereto.

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AU2003218735B2 (en) * 2002-03-13 2009-03-12 Janssen Pharmaceutica N.V. Piperazinyl-, piperidinyl- and morpholinyl-derivatives as novel inhibitors of histone deacetylase
US7629343B2 (en) * 2002-04-03 2009-12-08 Topotarget Uk Limited Carbamic acid compounds comprising a piperazine linkage as HDAC inhibitors
US20040072802A1 (en) * 2002-10-09 2004-04-15 Jingwu Duan Beta-amino acid derivatives as inhibitors of matrix metalloproteases and TNF-alpha
US7723376B2 (en) * 2003-07-15 2010-05-25 Korea Research Institute Of Bioscience And Biotechnology 2-oxo-heterocyclic compounds and pharmaceutical compositions
EP1685094A4 (en) * 2003-10-27 2007-08-22 S Bio Pte Ltd HYDROXAMATES CONNECTED TO ACYLUREE AND SULFONYLUREE

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CR9431A (es) 2008-07-31
EA012909B1 (ru) 2010-02-26
ITFI20050041A1 (it) 2006-09-16
MA29389B1 (fr) 2008-04-01
WO2006097460A8 (en) 2007-11-01
BRPI0606290A2 (pt) 2009-06-09
AP2007004188A0 (en) 2007-10-31
CO6321134A2 (es) 2011-09-20
EA200701970A1 (ru) 2008-02-28
TW200724529A (en) 2007-07-01
WO2006097460A1 (en) 2006-09-21
ZA200708749B (en) 2009-08-26
SA06270135B1 (ar) 2009-07-19
IL185882A0 (en) 2008-01-06
EP1868997A1 (en) 2007-12-26
CN101155780A (zh) 2008-04-02
US20080207694A1 (en) 2008-08-28
KR20070112240A (ko) 2007-11-22
JP2008533091A (ja) 2008-08-21
AU2006224624A1 (en) 2006-09-21
MX2007011072A (es) 2007-10-08
CA2600528A1 (en) 2006-09-21
NO20075281L (no) 2007-10-15
ITFI20050239A1 (it) 2007-05-22

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