MX356644B - Derivados de 2-fenilaminopirimidina como moduladores de proteina cinasa 2 rica en unidades repetitivas de leucina (lrrk2) para el tratamiento de la enfermedad de parkinson. - Google Patents

Derivados de 2-fenilaminopirimidina como moduladores de proteina cinasa 2 rica en unidades repetitivas de leucina (lrrk2) para el tratamiento de la enfermedad de parkinson.

Info

Publication number
MX356644B
MX356644B MX2014006027A MX2014006027A MX356644B MX 356644 B MX356644 B MX 356644B MX 2014006027 A MX2014006027 A MX 2014006027A MX 2014006027 A MX2014006027 A MX 2014006027A MX 356644 B MX356644 B MX 356644B
Authority
MX
Mexico
Prior art keywords
parkinson
disease
treatment
phenylaminopyrimidine derivatives
lrrk2 modulators
Prior art date
Application number
MX2014006027A
Other languages
English (en)
Other versions
MX2014006027A (es
Inventor
Wang Shumei
Chen Huifen
Baker-Glenn Charles
Chambers Mark
K Chan Bryan
Estrada Anthony
Sweeney Zachary
Jon Burdick Daniel
Gunzner-Toste Janet
Shore Daniel
Zhao Guiling
Original Assignee
Genentech Inc
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 Genentech Inc filed Critical Genentech Inc
Publication of MX2014006027A publication Critical patent/MX2014006027A/es
Publication of MX356644B publication Critical patent/MX356644B/es

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/48—Two nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D498/18—Bridged systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • 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
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • 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
    • C07D405/12—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 chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • 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
    • C07D405/14—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 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
    • C07D413/12—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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/10—Spiro-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biomedical Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Neurosurgery (AREA)
  • Epidemiology (AREA)
  • Psychology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Abstract

La presente invención se refiere a compuestos específicos de la fórmula I: (Ver Fórmula) o sales farmacéuticamente aceptables de los mismos, en donde m, X, R1, R2, R3, R5, R6 y R7 tienen los significados aquí definidos. Se describen también método de preparación de los compuestos y de utilización de los compuestos para el tratamiento de enfermedades asociadas con el receptor de la LRRK2, por ejemplo la enfermedad de Parkinson.
MX2014006027A 2011-11-29 2012-11-28 Derivados de 2-fenilaminopirimidina como moduladores de proteina cinasa 2 rica en unidades repetitivas de leucina (lrrk2) para el tratamiento de la enfermedad de parkinson. MX356644B (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201161564760P 2011-11-29 2011-11-29
PCT/EP2012/073762 WO2013079494A1 (en) 2011-11-29 2012-11-28 2-phenylaminopyrimidine derivatives as kinase lrrk2 modulators for the treatment of parkinson's disease

Publications (2)

Publication Number Publication Date
MX2014006027A MX2014006027A (es) 2014-06-04
MX356644B true MX356644B (es) 2018-06-07

Family

ID=47257804

Family Applications (1)

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MX2014006027A MX356644B (es) 2011-11-29 2012-11-28 Derivados de 2-fenilaminopirimidina como moduladores de proteina cinasa 2 rica en unidades repetitivas de leucina (lrrk2) para el tratamiento de la enfermedad de parkinson.

Country Status (14)

Country Link
US (1) US8809331B2 (es)
EP (1) EP2785699B1 (es)
JP (1) JP6104268B2 (es)
KR (1) KR102088072B1 (es)
CN (2) CN103987698B (es)
AR (1) AR089182A1 (es)
BR (1) BR112014012217B1 (es)
CA (1) CA2850593C (es)
ES (1) ES2644566T3 (es)
HK (1) HK1195309A1 (es)
MX (1) MX356644B (es)
RU (1) RU2661197C2 (es)
TW (1) TW201329051A (es)
WO (1) WO2013079494A1 (es)

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LT3124483T (lt) * 2010-11-10 2019-09-25 Genentech, Inc. Pirazolo aminopirimidino dariniai, kaip lrrk2 moduliatoriai
US20140228384A1 (en) * 2011-11-29 2014-08-14 Genentech, Inc. Assays and biomarkers for lrrk2
US8796296B2 (en) * 2011-11-29 2014-08-05 Genentech, Inc. Aminopyrimidine derivatives as LRRK2 modulators
WO2013079495A1 (en) * 2011-11-29 2013-06-06 F. Hoffmann-La Roche Ag 2-(phenyl or pyrid-3-yl) aminopyrimidine derivatives as kinase lrrk2 modulators for the treatment of parkinson's disease
WO2013164323A1 (en) * 2012-05-03 2013-11-07 F. Hoffmann-La Roche Ag Pyrazole aminopyrimidine derivatives as lrrk2 modulators for use in the treatment of parkinson's disease
AR099376A1 (es) 2013-12-20 2016-07-20 Signal Pharm Llc Compuestos de diaminopirimidilo sustituidos, sus composiciones y métodos de tratamiento con aquellos
WO2015176010A1 (en) 2014-05-15 2015-11-19 The United States Of America, As Represented By The Secretary, Departmentof Health & Human Services Treatment or prevention of an intestinal disease or disorder
EP3166637B1 (en) 2014-07-10 2020-01-29 The J. David Gladstone Institutes Compositions and methods for treating dengue virus infection
WO2017087905A1 (en) 2015-11-20 2017-05-26 Denali Therapeutics Inc. Compound, compositions, and methods
US11028080B2 (en) 2016-03-11 2021-06-08 Denali Therapeutics Inc. Substituted pyrimidines as LRKK2 inhibitors
HRP20211923T1 (hr) 2016-06-16 2022-03-04 Denali Therapeutics Inc. Pirimidin-2-ilamino-1h-pirazoli kao inhibitori lrrk2 za uporabu u liječenju neurodegenerativnih poremećaja
EP3475263B1 (en) 2016-06-27 2022-12-28 Rigel Pharmaceuticals, Inc. 2,4-diamino-pyrimidine compounds and their use as irak4 inhibitors
MA51222A (fr) 2017-11-21 2020-10-07 Denali Therapeutics Inc Polymorphes et formes solides d'un composé de pyrimidinylamino-pyrazole, et procédés de production
JP7284172B2 (ja) 2017-12-20 2023-05-30 デナリ セラピューティクス インコーポレイテッド ピリミジニル－４－アミノピラゾール化合物の調製方法
KR102063155B1 (ko) 2018-04-11 2020-01-08 한국과학기술연구원 우수한 카이네이즈 저해 활성을 보이는 다양한 치환기를 갖는 피리미딘 유도체
US20210361774A1 (en) * 2018-10-16 2021-11-25 Dana-Farber Cancer Institute, Inc. Degraders of wild-type and mutant forms of lrrk2
CN111732548B (zh) * 2020-06-11 2022-06-17 浙江大学 N2-氨甲酰芳环-2-氨基嘧啶类衍生物及其医药用途
CN116685325A (zh) 2020-10-20 2023-09-01 豪夫迈·罗氏有限公司 Pd-1轴结合拮抗剂和lrrk2抑制剂的组合疗法
WO2022216097A1 (ko) * 2021-04-08 2022-10-13 주식회사 스탠다임 신규한 lrrk2 억제제
US20240174647A1 (en) * 2022-09-30 2024-05-30 Neuron23, Inc. Kinase modulators and methods of use thereof
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WO2024112746A1 (en) 2022-11-22 2024-05-30 Denali Therapeutics Inc. Processes and intermediates for the preparation of a pyrimidine aminopyrazole compound

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LT3124483T (lt) 2010-11-10 2019-09-25 Genentech, Inc. Pirazolo aminopirimidino dariniai, kaip lrrk2 moduliatoriai
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WO2013079495A1 (en) * 2011-11-29 2013-06-06 F. Hoffmann-La Roche Ag 2-(phenyl or pyrid-3-yl) aminopyrimidine derivatives as kinase lrrk2 modulators for the treatment of parkinson's disease
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Also Published As

Publication number Publication date
TW201329051A (zh) 2013-07-16
JP2015501810A (ja) 2015-01-19
US8809331B2 (en) 2014-08-19
US20130157999A1 (en) 2013-06-20
CN105801493A (zh) 2016-07-27
CN105801493B (zh) 2018-09-21
EP2785699A1 (en) 2014-10-08
EP2785699B1 (en) 2017-09-06
AR089182A1 (es) 2014-08-06
RU2014124950A (ru) 2016-01-27
ES2644566T3 (es) 2017-11-29
KR20140097496A (ko) 2014-08-06
KR102088072B1 (ko) 2020-03-11
CA2850593A1 (en) 2013-06-06
RU2661197C2 (ru) 2018-07-13
CN103987698B (zh) 2016-04-20
CA2850593C (en) 2020-03-10
WO2013079494A1 (en) 2013-06-06
BR112014012217A2 (pt) 2017-05-30
BR112014012217B1 (pt) 2022-06-21
CN103987698A (zh) 2014-08-13
JP6104268B2 (ja) 2017-03-29
HK1195309A1 (zh) 2014-11-07
MX2014006027A (es) 2014-06-04

Similar Documents

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