EA023824B1 - ПРОИЗВОДНЫЕ 3,4-ДИГИДРОПИРРОЛО[1,2-a]ПИРАЗИН-1-ИЛАМИНА, ПРИГОДНЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ БЕТА-СЕКРЕТАЗЫ (BACE) - Google Patents
ПРОИЗВОДНЫЕ 3,4-ДИГИДРОПИРРОЛО[1,2-a]ПИРАЗИН-1-ИЛАМИНА, ПРИГОДНЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ БЕТА-СЕКРЕТАЗЫ (BACE) Download PDFInfo
- Publication number
- EA023824B1 EA023824B1 EA201391296A EA201391296A EA023824B1 EA 023824 B1 EA023824 B1 EA 023824B1 EA 201391296 A EA201391296 A EA 201391296A EA 201391296 A EA201391296 A EA 201391296A EA 023824 B1 EA023824 B1 EA 023824B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- group
- dementia
- alkyl
- compound according
- heteroaryl
- Prior art date
Links
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 title abstract description 5
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 title abstract description 5
- 239000003112 inhibitor Substances 0.000 title abstract 2
- MBVCQKKUMUXAMH-UHFFFAOYSA-N 3,4-dihydropyrrolo[1,2-a]pyrazin-1-amine Chemical class NC1=NCCN2C=CC=C12 MBVCQKKUMUXAMH-UHFFFAOYSA-N 0.000 title description 2
- 206010012289 Dementia Diseases 0.000 claims abstract description 19
- 150000001875 compounds Chemical class 0.000 claims abstract description 14
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- 201000010374 Down Syndrome Diseases 0.000 claims abstract description 4
- 208000018737 Parkinson disease Diseases 0.000 claims abstract description 4
- 208000010877 cognitive disease Diseases 0.000 claims abstract description 4
- 208000027061 mild cognitive impairment Diseases 0.000 claims abstract description 4
- 102000013455 Amyloid beta-Peptides Human genes 0.000 claims abstract description 3
- 108010090849 Amyloid beta-Peptides Proteins 0.000 claims abstract description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 3
- 208000035475 disorder Diseases 0.000 claims abstract description 3
- 230000002265 prevention Effects 0.000 claims abstract description 3
- 230000008033 biological extinction Effects 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims 8
- 125000003118 aryl group Chemical group 0.000 claims 6
- -1 chloro, fluoro, cyano, methyl Chemical group 0.000 claims 6
- 229910052736 halogen Inorganic materials 0.000 claims 6
- 150000002367 halogens Chemical class 0.000 claims 6
- 125000001072 heteroaryl group Chemical group 0.000 claims 6
- 229910052739 hydrogen Inorganic materials 0.000 claims 6
- 239000001257 hydrogen Substances 0.000 claims 6
- 125000001424 substituent group Chemical group 0.000 claims 5
- 125000003545 alkoxy group Chemical group 0.000 claims 4
- 150000002431 hydrogen Chemical class 0.000 claims 4
- 150000003839 salts Chemical class 0.000 claims 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 3
- 125000004076 pyridyl group Chemical group 0.000 claims 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- 239000013256 coordination polymer Substances 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 239000000460 chlorine Substances 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims 1
- 229910052731 fluorine Inorganic materials 0.000 claims 1
- 239000011737 fluorine Substances 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 125000003226 pyrazolyl group Chemical group 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- 102100021257 Beta-secretase 1 Human genes 0.000 abstract description 6
- 101000894895 Homo sapiens Beta-secretase 1 Proteins 0.000 abstract description 4
- 239000000203 mixture Substances 0.000 abstract description 4
- 108090000790 Enzymes Proteins 0.000 abstract description 2
- 102000004190 Enzymes Human genes 0.000 abstract description 2
- IXHBTMCLRNMKHZ-LBPRGKRZSA-N levobunolol Chemical compound O=C1CCCC2=C1C=CC=C2OC[C@@H](O)CNC(C)(C)C IXHBTMCLRNMKHZ-LBPRGKRZSA-N 0.000 abstract description 2
- 101710150192 Beta-secretase 1 Proteins 0.000 abstract 2
- 206010067889 Dementia with Lewy bodies Diseases 0.000 abstract 1
- 201000002832 Lewy body dementia Diseases 0.000 abstract 1
- 206010039966 Senile dementia Diseases 0.000 abstract 1
- 206010044688 Trisomy 21 Diseases 0.000 abstract 1
- 239000002439 beta secretase inhibitor Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
Classifications
-
- 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
-
- 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
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- 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
- A61P25/28—Drugs 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
-
- 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
Landscapes
- 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)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11157418 | 2011-03-09 | ||
| PCT/EP2012/053863 WO2012120023A1 (en) | 2011-03-09 | 2012-03-07 | 3,4-DIHYDRO-PYRROLO[1,2-a]PYRAZIN-1-YLAMINE DERIVATIVES USEFUL AS INHIBITORS OF BETA-SECRETASE (BACE) |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201391296A1 EA201391296A1 (ru) | 2014-01-30 |
| EA023824B1 true EA023824B1 (ru) | 2016-07-29 |
Family
ID=43833325
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201391296A EA023824B1 (ru) | 2011-03-09 | 2012-03-07 | ПРОИЗВОДНЫЕ 3,4-ДИГИДРОПИРРОЛО[1,2-a]ПИРАЗИН-1-ИЛАМИНА, ПРИГОДНЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ БЕТА-СЕКРЕТАЗЫ (BACE) |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US9845326B2 (enExample) |
| EP (1) | EP2683721B1 (enExample) |
| JP (1) | JP5853035B2 (enExample) |
| KR (1) | KR102012675B1 (enExample) |
| CN (1) | CN103415521B (enExample) |
| AU (1) | AU2012224632B2 (enExample) |
| BR (1) | BR112013022917A2 (enExample) |
| CA (1) | CA2825620C (enExample) |
| CL (1) | CL2013002511A1 (enExample) |
| CO (1) | CO6751283A2 (enExample) |
| EA (1) | EA023824B1 (enExample) |
| ES (1) | ES2534973T3 (enExample) |
| IL (1) | IL228239A (enExample) |
| MX (1) | MX340031B (enExample) |
| MY (1) | MY163346A (enExample) |
| PH (1) | PH12013501805A1 (enExample) |
| SG (1) | SG193342A1 (enExample) |
| UA (1) | UA109687C2 (enExample) |
| WO (1) | WO2012120023A1 (enExample) |
| ZA (1) | ZA201306719B (enExample) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2006307314C1 (en) | 2005-10-25 | 2011-08-25 | Shionogi & Co., Ltd. | Aminodihydrothiazine derivative |
| JP5383483B2 (ja) | 2007-04-24 | 2014-01-08 | 塩野義製薬株式会社 | アルツハイマー症治療用医薬組成物 |
| ES2476605T3 (es) | 2007-04-24 | 2014-07-15 | Shionogi & Co., Ltd. | Derivados de aminohidrotiazina sustituidos con grupos cíclicos |
| AU2009258496B8 (en) | 2008-06-13 | 2014-06-26 | Shionogi & Co., Ltd. | Sulfur-containing heterocyclic derivative having beta-secretase-inhibiting activity |
| WO2010047372A1 (ja) | 2008-10-22 | 2010-04-29 | 塩野義製薬株式会社 | Bace1阻害活性を有する2-アミノピリミジン-4-オンおよび2-アミノピリジン誘導体 |
| UA110467C2 (uk) | 2009-12-11 | 2016-01-12 | Шионогі Енд Ко., Лтд. | Похідні оксазину |
| PH12012502377A1 (en) | 2010-06-09 | 2014-10-14 | Janssen Pharmaceutica Nv | 5,6-dihydro-2h-[1,4]oxazin-3-yl-amine derivatives useful as inhibitors of beta-secretase (bace) |
| CN103261199A (zh) | 2010-10-29 | 2013-08-21 | 盐野义制药株式会社 | 萘啶衍生物 |
| JP5766198B2 (ja) | 2010-10-29 | 2015-08-19 | 塩野義製薬株式会社 | 縮合アミノジヒドロピリミジン誘導体 |
| NZ610948A (en) | 2010-12-22 | 2014-06-27 | Janssen Pharmaceutica Nv | 5,6-dihydro-imidazo[1,2-a]pyrazin-8-ylamine derivatives useful as inhibitors of beta-secretase (bace) |
| JP5853033B2 (ja) | 2011-03-01 | 2016-02-09 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプJanssen Pharmaceutica Naamloze Vennootschap | β−セクレターゼ(BACE)の阻害剤として有用な6,7−ジヒドロ−ピラゾロ[1,5−a]ピラジン−4−イルアミン誘導体 |
| BR112013022917A2 (pt) | 2011-03-09 | 2016-12-06 | Janssen Pharmaceutica Nv | derivados 3,4-dihidro-pirrolo[1,2-a]pirazino-1-ilamina úteis como inibidores de beta-secretase (bace) |
| CN103608345A (zh) | 2011-04-26 | 2014-02-26 | 盐野义制药株式会社 | 噁嗪衍生物和含有该噁嗪衍生物的bace1抑制剂 |
| EP2912035A4 (en) | 2012-10-24 | 2016-06-15 | Shionogi & Co | DERIVATIVES OF DIHYDROOXAZINE OR OXAZEPINE HAVING BACE1 INHIBITING ACTIVITY |
| KR102243133B1 (ko) * | 2013-06-12 | 2021-04-22 | 얀센 파마슈티카 엔.브이. | 베타-세크레타제(bace) 저해제로서의 4-아미노-6-페닐-6,7-디하이드로[1,2,3]트리아졸로[1,5-a]피라진 유도체 |
| JP6325092B2 (ja) * | 2013-06-12 | 2018-05-16 | ヤンセン ファーマシューティカ エヌ.ベー. | βーセクレターゼ(BACE)の阻害剤としての4−アミノ−6−フェニル−5,6−ジヒドロイミダゾ[1,5−A]ピラジン誘導体 |
| KR102243135B1 (ko) * | 2013-06-12 | 2021-04-22 | 얀센 파마슈티카 엔.브이. | 베타-세크레타제(bace) 저해제로서의 4-아미노-6-페닐-5,6-디하이드로이미다조[1,5-a]피라진-3(2h)-온 유도체 |
| RU2572076C2 (ru) * | 2014-03-26 | 2015-12-27 | Федеральное государственное бюджетное научное учреждение "Научно-исследовательский институт фармакологии имени В.В. Закусова" | 1-арилпирроло[1,2-a]пиразин-3-карбоксамиды с нейропсихотропной активностью |
| EP3233834B1 (en) | 2014-12-18 | 2019-11-13 | Janssen Pharmaceutica NV | 2,3,4,5-tetrahydropyridin-6-amine and 3,4-dihydro-2h-pyrrol-5-amine derivatives useful as inhibitors of beta-secretase |
| WO2018165520A1 (en) | 2017-03-10 | 2018-09-13 | Vps-3, Inc. | Metalloenzyme inhibitor compounds |
| CN117471007B (zh) * | 2023-10-31 | 2024-08-09 | 广东省中医院(广州中医药大学第二附属医院、广州中医药大学第二临床医学院、广东省中医药科学院) | 一种血浆β-淀粉样蛋白检测方法 |
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| WO2009022961A1 (en) * | 2007-05-15 | 2009-02-19 | Astrazeneca Ab | Pyrrolopyridine derivatives and their use as bace inhibitors |
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| US9242943B2 (en) | 2011-01-18 | 2016-01-26 | Siena Biotech S.P.A. | 1,4 oxazines as BACE1 and/or BACE2 inhibitors |
| JP5853033B2 (ja) | 2011-03-01 | 2016-02-09 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプJanssen Pharmaceutica Naamloze Vennootschap | β−セクレターゼ(BACE)の阻害剤として有用な6,7−ジヒドロ−ピラゾロ[1,5−a]ピラジン−4−イルアミン誘導体 |
| BR112013022917A2 (pt) * | 2011-03-09 | 2016-12-06 | Janssen Pharmaceutica Nv | derivados 3,4-dihidro-pirrolo[1,2-a]pirazino-1-ilamina úteis como inibidores de beta-secretase (bace) |
| CN103608345A (zh) | 2011-04-26 | 2014-02-26 | 盐野义制药株式会社 | 噁嗪衍生物和含有该噁嗪衍生物的bace1抑制剂 |
| IN2014DN03206A (enExample) | 2011-10-13 | 2015-05-22 | Novartis Ag | |
| UA111749C2 (uk) | 2011-12-05 | 2016-06-10 | Янссен Фармацевтика Нв | Похідні 6-дифторметил-5,6-дигідро-2h-[1,4]оксазин-3-аміну |
| JP5989130B2 (ja) | 2011-12-06 | 2016-09-07 | ヤンセン ファーマシューティカ エヌ.ベー. | 5−(3−アミノフェニル)−5−アルキル−5,6−ジヒドロ−2h−[1,4]オキサジン−3−アミン誘導体 |
| AU2013363151A1 (en) | 2012-12-20 | 2015-06-04 | Merck Sharp & Dohme Corp. | C5, C6 oxacyclic-fused iminothiazine dioxide compounds as BACE inhibitors |
| JP6325092B2 (ja) | 2013-06-12 | 2018-05-16 | ヤンセン ファーマシューティカ エヌ.ベー. | βーセクレターゼ(BACE)の阻害剤としての4−アミノ−6−フェニル−5,6−ジヒドロイミダゾ[1,5−A]ピラジン誘導体 |
| KR102243133B1 (ko) | 2013-06-12 | 2021-04-22 | 얀센 파마슈티카 엔.브이. | 베타-세크레타제(bace) 저해제로서의 4-아미노-6-페닐-6,7-디하이드로[1,2,3]트리아졸로[1,5-a]피라진 유도체 |
| KR102243135B1 (ko) | 2013-06-12 | 2021-04-22 | 얀센 파마슈티카 엔.브이. | 베타-세크레타제(bace) 저해제로서의 4-아미노-6-페닐-5,6-디하이드로이미다조[1,5-a]피라진-3(2h)-온 유도체 |
| EP3233834B1 (en) | 2014-12-18 | 2019-11-13 | Janssen Pharmaceutica NV | 2,3,4,5-tetrahydropyridin-6-amine and 3,4-dihydro-2h-pyrrol-5-amine derivatives useful as inhibitors of beta-secretase |
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2012
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- 2012-03-07 JP JP2013557074A patent/JP5853035B2/ja not_active Expired - Fee Related
- 2012-03-07 MY MYPI2013003278A patent/MY163346A/en unknown
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- 2012-03-07 EA EA201391296A patent/EA023824B1/ru not_active IP Right Cessation
- 2012-03-07 PH PH1/2013/501805A patent/PH12013501805A1/en unknown
- 2012-03-07 MX MX2013010280A patent/MX340031B/es active IP Right Grant
- 2012-03-07 WO PCT/EP2012/053863 patent/WO2012120023A1/en not_active Ceased
- 2012-03-07 EP EP12707319.5A patent/EP2683721B1/en not_active Not-in-force
- 2012-03-07 KR KR1020137022396A patent/KR102012675B1/ko not_active Expired - Fee Related
- 2012-03-07 SG SG2013067210A patent/SG193342A1/en unknown
- 2012-03-07 US US14/003,901 patent/US9845326B2/en active Active
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- 2012-03-07 ES ES12707319.5T patent/ES2534973T3/es active Active
- 2012-03-07 AU AU2012224632A patent/AU2012224632B2/en not_active Ceased
- 2012-07-03 UA UAA201308782A patent/UA109687C2/ru unknown
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- 2013-08-30 CL CL2013002511A patent/CL2013002511A1/es unknown
- 2013-09-02 IL IL228239A patent/IL228239A/en active IP Right Grant
- 2013-09-06 ZA ZA2013/06719A patent/ZA201306719B/en unknown
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| WO2006076284A2 (en) * | 2005-01-14 | 2006-07-20 | Wyeth | AMINO-IMIDAZOLONES FOR THE INHIBITION OF ß-SECRETASE |
| WO2009022961A1 (en) * | 2007-05-15 | 2009-02-19 | Astrazeneca Ab | Pyrrolopyridine derivatives and their use as bace inhibitors |
Also Published As
| Publication number | Publication date |
|---|---|
| MY163346A (en) | 2017-09-15 |
| JP5853035B2 (ja) | 2016-02-09 |
| CA2825620A1 (en) | 2012-09-13 |
| JP2014507455A (ja) | 2014-03-27 |
| NZ615720A (en) | 2014-08-29 |
| AU2012224632B2 (en) | 2016-06-16 |
| WO2012120023A1 (en) | 2012-09-13 |
| MX2013010280A (es) | 2013-10-01 |
| CA2825620C (en) | 2019-04-23 |
| KR102012675B1 (ko) | 2019-08-21 |
| PH12013501805A1 (en) | 2013-11-18 |
| BR112013022917A2 (pt) | 2016-12-06 |
| ZA201306719B (en) | 2015-04-29 |
| UA109687C2 (xx) | 2015-09-25 |
| IL228239A (en) | 2016-06-30 |
| CN103415521B (zh) | 2016-01-06 |
| IL228239A0 (en) | 2013-11-25 |
| SG193342A1 (en) | 2013-10-30 |
| MX340031B (es) | 2016-06-21 |
| KR20140019332A (ko) | 2014-02-14 |
| EP2683721B1 (en) | 2015-01-28 |
| US20130345228A1 (en) | 2013-12-26 |
| EA201391296A1 (ru) | 2014-01-30 |
| ES2534973T3 (es) | 2015-04-30 |
| HK1189223A1 (zh) | 2014-05-30 |
| US9845326B2 (en) | 2017-12-19 |
| CN103415521A (zh) | 2013-11-27 |
| EP2683721A1 (en) | 2014-01-15 |
| AU2012224632A1 (en) | 2013-08-01 |
| CL2013002511A1 (es) | 2014-01-24 |
| CO6751283A2 (es) | 2013-09-16 |
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