MX2015001899A - Inhibidores de la replicacion del virus de la inmunodeficiencia humana. - Google Patents
Inhibidores de la replicacion del virus de la inmunodeficiencia humana.Info
- Publication number
- MX2015001899A MX2015001899A MX2015001899A MX2015001899A MX2015001899A MX 2015001899 A MX2015001899 A MX 2015001899A MX 2015001899 A MX2015001899 A MX 2015001899A MX 2015001899 A MX2015001899 A MX 2015001899A MX 2015001899 A MX2015001899 A MX 2015001899A
- Authority
- MX
- Mexico
- Prior art keywords
- butoxy
- tert
- acetic
- dioxa
- tetraazahexacyclo
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title claims abstract description 66
- 241000725303 Human immunodeficiency virus Species 0.000 title abstract description 26
- 230000029812 viral genome replication Effects 0.000 title description 4
- 239000000203 mixture Substances 0.000 claims abstract description 232
- 150000001875 compounds Chemical class 0.000 claims abstract description 93
- 208000015181 infectious disease Diseases 0.000 claims abstract description 12
- 208000031886 HIV Infections Diseases 0.000 claims abstract description 9
- 208000037357 HIV infectious disease Diseases 0.000 claims abstract description 9
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims abstract description 9
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 394
- -1 homopiperidinyl Chemical group 0.000 claims description 180
- 239000002253 acid Substances 0.000 claims description 161
- 125000000217 alkyl group Chemical group 0.000 claims description 56
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 50
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 37
- 150000003839 salts Chemical class 0.000 claims description 33
- 125000005843 halogen group Chemical group 0.000 claims description 32
- 239000003795 chemical substances by application Substances 0.000 claims description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims description 28
- 239000001257 hydrogen Substances 0.000 claims description 28
- 125000001424 substituent group Chemical group 0.000 claims description 27
- 125000003545 alkoxy group Chemical group 0.000 claims description 26
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 25
- 125000001188 haloalkyl group Chemical group 0.000 claims description 25
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 24
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 22
- 208000030507 AIDS Diseases 0.000 claims description 15
- 239000002777 nucleoside Substances 0.000 claims description 14
- 125000003386 piperidinyl group Chemical group 0.000 claims description 14
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 12
- 108010078851 HIV Reverse Transcriptase Proteins 0.000 claims description 11
- 125000004450 alkenylene group Chemical group 0.000 claims description 11
- 125000002947 alkylene group Chemical group 0.000 claims description 11
- 125000005434 dihydrobenzoxazinyl group Chemical group O1N(CCC2=C1C=CC=C2)* 0.000 claims description 9
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 claims description 8
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 claims description 8
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 claims description 8
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 230000035800 maturation Effects 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 102100034343 Integrase Human genes 0.000 claims description 7
- 125000002393 azetidinyl group Chemical group 0.000 claims description 7
- 125000002757 morpholinyl group Chemical group 0.000 claims description 7
- 125000004193 piperazinyl group Chemical group 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 5
- 108010061833 Integrases Proteins 0.000 claims description 4
- 239000002835 hiv fusion inhibitor Substances 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
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- 239000004030 hiv protease inhibitor Substances 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- HBZVNWNSRNTWPS-UHFFFAOYSA-N 6-amino-4-hydroxynaphthalene-2-sulfonic acid Chemical compound C1=C(S(O)(=O)=O)C=C(O)C2=CC(N)=CC=C21 HBZVNWNSRNTWPS-UHFFFAOYSA-N 0.000 claims 2
- 241001124076 Aphididae Species 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 167
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- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 100
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 95
- 239000000543 intermediate Substances 0.000 description 93
- 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 description 92
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 87
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- RUZLIIJDZBWWSA-INIZCTEOSA-N methyl 2-[[(1s)-1-(7-methyl-2-morpholin-4-yl-4-oxopyrido[1,2-a]pyrimidin-9-yl)ethyl]amino]benzoate Chemical group COC(=O)C1=CC=CC=C1N[C@@H](C)C1=CC(C)=CN2C(=O)C=C(N3CCOCC3)N=C12 RUZLIIJDZBWWSA-INIZCTEOSA-N 0.000 description 68
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- 238000002953 preparative HPLC Methods 0.000 description 43
- 239000007832 Na2SO4 Substances 0.000 description 41
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 41
- 229910052938 sodium sulfate Inorganic materials 0.000 description 41
- 235000011152 sodium sulphate Nutrition 0.000 description 41
- 239000012267 brine Substances 0.000 description 40
- 239000012044 organic layer Substances 0.000 description 40
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 40
- 229920006395 saturated elastomer Polymers 0.000 description 34
- 230000002829 reductive effect Effects 0.000 description 33
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
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Classifications
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- 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
- A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/22—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed systems contains four or more hetero rings
-
- 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
- C07D487/12—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 three hetero rings
- C07D487/16—Peri-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
- C07D491/22—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 four or more hetero rings
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- 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
- C07D498/16—Peri-condensed 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
- C07D498/22—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 four or more hetero rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Communicable Diseases (AREA)
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- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| US201361818572P | 2013-05-02 | 2013-05-02 | |
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| PCT/US2013/054532 WO2014028384A1 (en) | 2012-08-16 | 2013-08-12 | Inhibitors of human immunodeficiency virus replication |
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| PH12013500011A1 (en) | 2010-07-02 | 2013-02-18 | Gilead Sciences Inc | Napht-2-ylacetic acid derivatives to treat aids |
| NZ604716A (en) | 2010-07-02 | 2014-12-24 | Gilead Sciences Inc | 2-quinolinyl-acetic acid derivatives as hiv antiviral compounds |
| JP5918848B2 (ja) | 2011-04-21 | 2016-05-18 | ギリアード サイエンシーズ， インコーポレイテッド | ベンゾチアゾール化合物およびその薬学的使用 |
| US9284323B2 (en) | 2012-01-04 | 2016-03-15 | Gilead Sciences, Inc. | Naphthalene acetic acid derivatives against HIV infection |
| US9376392B2 (en) | 2012-01-04 | 2016-06-28 | Gilead Sciences, Inc. | 2-(tert-butoxy)-2-(7-methylquinolin-6-yl) acetic acid derivatives for treating AIDS |
| US8987250B2 (en) | 2012-04-20 | 2015-03-24 | Gilead Sciences, Inc. | Therapeutic compounds |
| US8906929B2 (en) | 2012-08-16 | 2014-12-09 | Bristol-Myers Squibb Company | Inhibitors of human immunodeficiency virus replication |
| JP2016516692A (ja) * | 2013-03-13 | 2016-06-09 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | ヒト免疫不全ウイルス複製の阻害剤 |
| EP2970297A1 (en) * | 2013-03-14 | 2016-01-20 | Bristol-Myers Squibb Company | Inhibitors of human immunodeficiency virus replication |
| PT3105236T (pt) | 2014-02-12 | 2017-12-22 | Viiv Healthcare Uk (No 5) Ltd | Macrociclos de benzotiazole como inibidores da replicação do vírus da imunodeficiência humana |
| WO2015123182A1 (en) * | 2014-02-12 | 2015-08-20 | Bristol-Myers Squibb Company | Pyrazolopyrimidine macrocycles as inhibitors of human immunodeficiency virus replication |
| WO2015126758A1 (en) * | 2014-02-18 | 2015-08-27 | Bristol-Myers Squibb Company | Imidazopyrimidine macrocycles as inhibitors of human immunodeficiency virus replication |
| EP3152215A1 (en) * | 2014-02-18 | 2017-04-12 | ViiV Healthcare UK (No.5) Limited | Pyrazolopyrimidine macrocycles as inhibitors of human immunodeficiency virus replication |
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| WO2015126765A1 (en) | 2014-02-19 | 2015-08-27 | Bristol-Myers Squibb Company | Inhibitors of human immunodeficiency virus replication |
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| US10125148B2 (en) * | 2014-02-19 | 2018-11-13 | Viiv Healthcare Uk (No. 5) Limited | Pyrazolopyrimidine macrocycles as inhibitors of human immunodeficiency virus replication |
| EP3116880B1 (en) | 2014-02-20 | 2018-03-21 | VIIV Healthcare UK (No.5) Limited | Pyridin-3-yl acetic acid macrocycles as inhibitors of human immunodeficiency virus replication |
| WO2015174511A1 (ja) * | 2014-05-16 | 2015-11-19 | 塩野義製薬株式会社 | Ｈｉｖ複製阻害作用を有する３環性複素環誘導体 |
| TWI700284B (zh) | 2015-05-29 | 2020-08-01 | 日商塩野義製藥股份有限公司 | 具有ｈｉｖ複製抑制作用之含氮３環性衍生物 |
| EP3334741A1 (en) * | 2015-08-10 | 2018-06-20 | VIIV Healthcare UK (No.5) Limited | Imidazopyridine macrocycles as inhibitors of human immunodeficiency virus replication |
| CA3057261A1 (en) | 2017-04-06 | 2018-10-11 | Inventiva | New compounds inhibitors of the yap/taz-tead interaction and their use in the treatment of malignant mesothelioma |
| EP3632908A1 (en) | 2018-10-02 | 2020-04-08 | Inventiva | Inhibitors of the yap/taz-tead interaction and their use in the treatment of cancer |
| PL3938047T3 (pl) | 2019-03-22 | 2022-11-07 | Gilead Sciences, Inc. | Zmostkowane tricykliczne związki karbamoilopirydonowe i ich zastosowanie farmaceutyczne |
| CR20220418A (es) | 2020-02-24 | 2022-10-10 | Gilead Sciences Inc | Compuestos tetracíclicos para el tratamiento de infecciones por vih |
| US12421235B2 (en) | 2020-09-30 | 2025-09-23 | Gilead Sciences, Inc. | Bridged tricyclic carbamoylpyridone compounds and uses thereof |
| PL4196479T3 (pl) | 2021-01-19 | 2024-03-18 | Gilead Sciences, Inc. | Podstawione związki pirydotriazynowe i ich zastosowania |
| TW202446773A (zh) | 2022-04-06 | 2024-12-01 | 美商基利科學股份有限公司 | 橋聯三環胺甲醯基吡啶酮化合物及其用途 |
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| GB427857A (en) | 1934-08-02 | 1935-05-01 | Newsum Sons & Company Ltd H | A new or improved system of construction for skeleton structures, particularly vehicle body frames and door frames |
| US7939545B2 (en) | 2006-05-16 | 2011-05-10 | Boehringer Ingelheim International Gmbh | Inhibitors of human immunodeficiency virus replication |
| KR20100108337A (ko) | 2007-11-15 | 2010-10-06 | 베링거 인겔하임 인터내셔날 게엠베하 | 사람 면역결핍 바이러스 복제의 억제제 |
| US8377960B2 (en) | 2007-11-15 | 2013-02-19 | Gilead Sciences, Inc. | Inhibitors of human immunodeficiency virus replication |
| NZ585226A (en) | 2007-11-16 | 2012-08-31 | Gilead Sciences Inc | Inhibitors of human immunodeficiency virus replication |
| CA2705338A1 (en) | 2007-11-16 | 2009-05-22 | Boehringer Ingelheim International Gmbh | Inhibitors of human immunodeficiency virus replication |
| CN101970741B (zh) | 2007-11-23 | 2014-09-03 | 皇家飞利浦电子股份有限公司 | 隔间 |
| TW200942243A (en) * | 2008-03-05 | 2009-10-16 | Biocryst Pharm Inc | Antiviral therapeutic agents |
| US8129398B2 (en) * | 2008-03-19 | 2012-03-06 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
| GB0813980D0 (en) | 2008-07-31 | 2008-09-10 | Univ St Andrews | Control of relaxation oscillations in intracavity optical parametric oscillato rs |
| JP5331404B2 (ja) | 2008-08-01 | 2013-10-30 | 国立大学法人 東京医科歯科大学 | 先天性異常症の染色体欠失の検出方法 |
| GB0908394D0 (en) | 2009-05-15 | 2009-06-24 | Univ Leuven Kath | Novel viral replication inhibitors |
| US8338441B2 (en) | 2009-05-15 | 2012-12-25 | Gilead Sciences, Inc. | Inhibitors of human immunodeficiency virus replication |
| GB0913636D0 (en) | 2009-08-05 | 2009-09-16 | Univ Leuven Kath | Novel viral replication inhibitors |
| WO2011049988A2 (en) * | 2009-10-20 | 2011-04-28 | Eiger Biopharmaceuticals, Inc. | Indazoles to treat flaviviridae virus infection |
| JP2013515692A (ja) | 2009-12-23 | 2013-05-09 | カトリック・ユニベルシティト・ルーヴァン | 新規抗ウイルス化合物 |
| JP5739517B2 (ja) * | 2010-04-02 | 2015-06-24 | ヤンセン・アールアンドデイ・アイルランド | 大環状インテグラーゼ阻害剤 |
| NZ604716A (en) | 2010-07-02 | 2014-12-24 | Gilead Sciences Inc | 2-quinolinyl-acetic acid derivatives as hiv antiviral compounds |
| PH12013500011A1 (en) | 2010-07-02 | 2013-02-18 | Gilead Sciences Inc | Napht-2-ylacetic acid derivatives to treat aids |
| US8633200B2 (en) | 2010-09-08 | 2014-01-21 | Bristol-Myers Squibb Company | Inhibitors of human immunodeficiency virus replication |
| CN105330675A (zh) | 2010-11-15 | 2016-02-17 | Viiv保健英国有限公司 | Hiv复制的抑制剂 |
| EP2640705A2 (en) * | 2010-11-15 | 2013-09-25 | Katholieke Universiteit Leuven | Novel antiviral compounds |
| US8791108B2 (en) | 2011-08-18 | 2014-07-29 | Bristol-Myers Squibb Company | Inhibitors of human immunodeficiency virus replication |
| US8629276B2 (en) | 2012-02-15 | 2014-01-14 | Bristol-Myers Squibb Company | Inhibitors of human immunodeficiency virus replication |
| US9034882B2 (en) | 2012-03-05 | 2015-05-19 | Bristol-Myers Squibb Company | Inhibitors of human immunodeficiency virus replication |
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| US8906929B2 (en) | 2012-08-16 | 2014-12-09 | Bristol-Myers Squibb Company | Inhibitors of human immunodeficiency virus replication |
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| AU2013302873B2 (en) | 2017-02-02 |
| WO2014028384A1 (en) | 2014-02-20 |
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| US8906929B2 (en) | 2014-12-09 |
| EP2888266B1 (en) | 2017-01-11 |
| SG11201500887QA (en) | 2015-03-30 |
| CA2882077A1 (en) | 2014-02-20 |
| KR20150042830A (ko) | 2015-04-21 |
| ES2619960T3 (es) | 2017-06-27 |
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