HRP20160713T1 - Postupak i intermedijarni proizvodi za pripravu agomelatina - Google Patents
Postupak i intermedijarni proizvodi za pripravu agomelatina Download PDFInfo
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- HRP20160713T1 HRP20160713T1 HRP20160713TT HRP20160713T HRP20160713T1 HR P20160713 T1 HRP20160713 T1 HR P20160713T1 HR P20160713T T HRP20160713T T HR P20160713TT HR P20160713 T HRP20160713 T HR P20160713T HR P20160713 T1 HRP20160713 T1 HR P20160713T1
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- 238000000034 method Methods 0.000 title claims 15
- YJYPHIXNFHFHND-UHFFFAOYSA-N agomelatine Chemical compound C1=CC=C(CCNC(C)=O)C2=CC(OC)=CC=C21 YJYPHIXNFHFHND-UHFFFAOYSA-N 0.000 title claims 5
- 229960002629 agomelatine Drugs 0.000 title claims 5
- 239000000543 intermediate Substances 0.000 title 1
- 230000002194 synthesizing effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 41
- 230000015572 biosynthetic process Effects 0.000 claims 18
- 238000003786 synthesis reaction Methods 0.000 claims 18
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims 9
- 238000006243 chemical reaction Methods 0.000 claims 4
- 238000007363 ring formation reaction Methods 0.000 claims 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 3
- 239000007868 Raney catalyst Substances 0.000 claims 3
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims 3
- 229910000564 Raney nickel Inorganic materials 0.000 claims 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 3
- 238000005899 aromatization reaction Methods 0.000 claims 3
- 229910052739 hydrogen Inorganic materials 0.000 claims 3
- 239000001257 hydrogen Substances 0.000 claims 3
- 150000003254 radicals Chemical class 0.000 claims 3
- 239000007787 solid Substances 0.000 claims 3
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 claims 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 2
- SJNALLRHIVGIBI-UHFFFAOYSA-N allyl cyanide Chemical compound C=CCC#N SJNALLRHIVGIBI-UHFFFAOYSA-N 0.000 claims 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims 2
- 239000003999 initiator Substances 0.000 claims 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- YIVJZNGAASQVEM-UHFFFAOYSA-N Lauroyl peroxide Chemical compound CCCCCCCCCCCC(=O)OOC(=O)CCCCCCCCCCC YIVJZNGAASQVEM-UHFFFAOYSA-N 0.000 claims 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims 1
- SMZOGRDCAXLAAR-UHFFFAOYSA-N aluminium isopropoxide Chemical compound [Al+3].CC(C)[O-].CC(C)[O-].CC(C)[O-] SMZOGRDCAXLAAR-UHFFFAOYSA-N 0.000 claims 1
- ZXVOCOLRQJZVBW-UHFFFAOYSA-N azane;ethanol Chemical compound N.CCO ZXVOCOLRQJZVBW-UHFFFAOYSA-N 0.000 claims 1
- 230000003197 catalytic effect Effects 0.000 claims 1
- 238000006297 dehydration reaction Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 238000007348 radical reaction Methods 0.000 claims 1
- 238000010992 reflux Methods 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 239000001632 sodium acetate Substances 0.000 claims 1
- 235000017281 sodium acetate Nutrition 0.000 claims 1
- UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 claims 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/06—Preparation of carboxylic acid amides from nitriles by transformation of cyano groups into carboxamide groups
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/18—Feminine contraceptives
-
- 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
- A61P25/06—Antimigraine agents
-
- 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
- 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
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/16—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
- C07C233/17—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/18—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
- C07C255/37—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by etherified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
- C07C255/40—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by doubly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Cardiology (AREA)
- Endocrinology (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Gynecology & Obstetrics (AREA)
- Heart & Thoracic Surgery (AREA)
- Reproductive Health (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Inorganic Compounds Of Heavy Metals (AREA)
- Catalysts (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Claims (18)
1. Postupak za industrijsku sintezu spoja formule (I):
[image]
naznačen time, da alil cijanid formule (II):
[image]
reagira, u nazočnosti pokretača slobodnih radikala, sa spojem formule (III):
[image]
pri čemu Xa predstavlja skupinu -S-C(S)-OR u kojoj R predstavlja ravnu ili razgrananu (C1-C6)alkilnu skupinu, kako bi se dobio spoj formule (IV):
[image]
gdje je Xa gore definiran,
pri čemu se ovaj potonji spoj po izboru može izolirati te se potom podvrgava cikliranju u nazočnosti pokretača slobodnog radikala kako bi se dobio spoj formule (V):
[image]
koji spoj formule (V) također po izboru može biti izoliran,
pri čemu je izložen reakciji redukcije-dehidracije kako bi se dobio spoj formule (VI):
[image]
koji se potom izlaže reakciji aromatizacije kako bi se dobio spoj formule (VII):
[image]
koji se izlaže redukciji uporabom hidrogena u nazočnosti Raney nikla u polarnom protonskom mediju te reakciji s octenim anhidridom kako bi se dobio spoj formule (I), koji je izoliran u obliku krutine.
2. Postupak za sintezu spoja formule (I) u skladu s patentnim zahtjevom 1, naznačen time, da se spoj formule (VII) potom izlaže redukciji uporabom hidrogena u nazočnosti Raney nikla u mediju amonij-etanola te se onda pretvara u sol uporabom klorovodične kiseline kako bi se dobio spoj formule (VIII):
[image]
koji je sukcesivno podvrgnut djelovanju natrijevog acetata a potom octenog anhidrida kako bi se dobio spoj formule (I), koji je izoliran u obliku krutine.
3. Postupak za sintezu spoja formule (I) u skladu s patentnim zahtjevom 1, naznačen time, da se spoj formule (VII) izložen redukciji uporabom hidrogena u nazočnosti Raney nikla u mediju koji se sastoji od octenog anhidrida u polarnom protonskom mediju kako bi se dobio spoj formule (I) koji je izoliran u obliku krutine.
4. Postupak za sintezu spoja formule (I) u skladu s patentnim zahtjevom 1, naznačen time, da skupina Xa = -S- C(S)-OC2H5.
5. Postupak za sintezu spoja formule (I) u skladu s patentnim zahtjevom 1, naznačen time, da su reakcije slobodnih radikala izazvane toplinskim sredstvima pri temperaturi od 50 do 140°C.
6. Postupak za sintezu spoja formule (I) u skladu s patentnim zahtjevom 1, naznačen time, da se cikliranje spoja formule (IV) izvodi pri temperaturi od 130 do 135°C.
7. Postupak za sintezu spoja formule (I) u skladu s patentnim zahtjevom 1, naznačen time, da se korak dodavanja spoja formule (II) spoju formule (III) te cikliranje spoja formule (IV) pokreće u nazočnosti dilauroil peroksida.
8. Postupak za sintezu spoja formule (I) u skladu s patentnim zahtjevom 1, naznačen time, da se korak dodavanja spoja formule (II) spoju formule (III) izvodi u klorobenzenu.
9. Postupak za sintezu spoja formule (I) u skladu s patentnim zahtjevom 1, naznačen time, da se korak cikliranja adukta formule (IV) kako bi nastao spoj formule (V) izvodi u etil acetatu.
10. Postupak sinteze u skladu s patentnim zahtjevom 1, naznačen time, da je pretvaranje spoja formule (V) u spoj formule (VI) izvedeno u nazočnosti aluminijevog izopropoksida.
11. Postupak sinteze u skladu s patentnim zahtjevom 1, naznačen time, da je pretvaranje spoja formule (V) u spoj formule (VI) izvedeno u izopropanolu.
12. Postupak sinteze u skladu s patentnim zahtjevom 1, naznačen time, da je katalitička količina p- toluenesulfonske kiseline dodana u smjesu na kraju pretvaranja spoja formule (V) u spoj formule (VI).
13. Postupak sinteze u skladu s patentnim zahtjevom 1, naznačen time, da se aromatizacija spoja formule (VI) izvodi u nazočnosti kinona.
14. Postupak sinteze u skladu s patentnim zahtjevom 1, naznačen time, da se aromatizacija spoja formule (VI) izvodi u nazočnosti tetraklorobenzokinona TCQ na refluksu toluena.
15. Spoj formule (V) u skladu s patentnim zahtjevom 1, naznačen time, da se koristi kao posrednik u sintezi agomelatina formule (I) u skladu s patentnim zahtjevom 1.
16. Uporaba spoja formule (V) u skladu s patentnim zahtjevom 15, naznačena time, da se koristi u sintezi agomelatina formule (I) u skladu s patentnim zahtjevom 1.
17. Spoj formule (VI) u skladu s patentnim zahtjevom 1, naznačen time, da se koristi kao posrednik u sintezi agomelatina formule (I) u skladu s patentnim zahtjevom 1.
18. Uporaba spoja formule (VI) u skladu s patentnim zahtjevom 17, naznačena time, da se koristi u sintezi agomelatina formule (I) u skladu s patentnim zahtjevom 1.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR1100024A FR2970000B1 (fr) | 2011-01-05 | 2011-01-05 | Nouveau procede de synthese de l'agomelatine |
| PCT/FR2012/000005 WO2012113999A1 (fr) | 2011-01-05 | 2012-01-04 | Procede et intermediaires de synthese de l ' agomelatine |
| EP12703858.6A EP2661422B9 (fr) | 2011-01-05 | 2012-01-04 | Procédé et intermédiaires de synthèse de l'agomélatine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20160713T1 true HRP20160713T1 (hr) | 2016-07-29 |
Family
ID=44088993
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20160713TT HRP20160713T1 (hr) | 2011-01-05 | 2016-06-21 | Postupak i intermedijarni proizvodi za pripravu agomelatina |
Country Status (43)
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103058879B (zh) * | 2012-12-20 | 2015-09-09 | 安徽悦康凯悦制药有限公司 | 阿戈美拉汀的制备方法 |
| CN104803882B (zh) * | 2014-01-26 | 2017-02-01 | 江西同和药业股份有限公司 | 一种化合物及其制备方法和应用 |
| CN107353229B (zh) * | 2017-08-08 | 2019-04-30 | 许昌恒生制药有限公司 | 一种阿戈美拉汀中间体的制备方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2658818B1 (fr) * | 1990-02-27 | 1993-12-31 | Adir Cie | Nouveaux derives a structure naphtalenique, leur procede de preparation et les compositions pharmaceutiques qui les contiennent. |
| FR2866334B1 (fr) | 2004-02-13 | 2006-05-26 | Servier Lab | Nouveau procede de synthese du (7-methoxy-1-naphtyl) acetonitrile et application a la synthese de l'agomelatine |
| FR2866335B1 (fr) * | 2004-02-13 | 2006-05-26 | Servier Lab | Nouveau procede de synthese de l'agomelatine |
| CN101486665B (zh) | 2009-03-03 | 2013-04-17 | 上海医药工业研究院 | 阿戈美拉汀中间体2-(7-甲氧基-1-萘基)乙酰胺的制备方法 |
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2011
- 2011-01-05 FR FR1100024A patent/FR2970000B1/fr not_active Expired - Fee Related
- 2011-12-20 JO JOP/2011/0392A patent/JO3200B1/ar active
- 2011-12-30 UY UY0001033845A patent/UY33845A/es unknown
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2012
- 2012-01-03 SA SA112330134A patent/SA112330134B1/ar unknown
- 2012-01-04 EA EA201300794A patent/EA022077B1/ru unknown
- 2012-01-04 CA CA2823587A patent/CA2823587C/fr active Active
- 2012-01-04 PL PL12703858.6T patent/PL2661422T3/pl unknown
- 2012-01-04 AR ARP120100020A patent/AR084780A1/es unknown
- 2012-01-04 GE GEAP201213180A patent/GEP20156365B/en unknown
- 2012-01-04 DK DK12703858.6T patent/DK2661422T3/en active
- 2012-01-04 US US13/977,799 patent/US8853449B2/en not_active Ceased
- 2012-01-04 SG SG2013046370A patent/SG191733A1/en unknown
- 2012-01-04 CU CUP2013000092A patent/CU24289B1/xx unknown
- 2012-01-04 AU AU2012220474A patent/AU2012220474B2/en not_active Ceased
- 2012-01-04 EP EP12703858.6A patent/EP2661422B9/fr active Active
- 2012-01-04 RU RU2013136344/04A patent/RU2550812C2/ru not_active IP Right Cessation
- 2012-01-04 ES ES12703858.6T patent/ES2583682T3/es active Active
- 2012-01-04 BR BR112013017307A patent/BR112013017307A2/pt not_active IP Right Cessation
- 2012-01-04 CN CN201280004746.9A patent/CN103313965B/zh not_active Expired - Fee Related
- 2012-01-04 US US14/619,284 patent/USRE46218E1/en active Active
- 2012-01-04 JP JP2013547894A patent/JP5837616B2/ja not_active Expired - Fee Related
- 2012-01-04 PE PE2013001435A patent/PE20140037A1/es active IP Right Grant
- 2012-01-04 KR KR1020137020469A patent/KR101543432B1/ko active IP Right Grant
- 2012-01-04 TW TW101100368A patent/TWI438180B/zh not_active IP Right Cessation
- 2012-01-04 HU HUE12703858A patent/HUE028471T2/en unknown
- 2012-01-04 RS RS20160320A patent/RS54753B9/sr unknown
- 2012-01-04 WO PCT/FR2012/000005 patent/WO2012113999A1/fr active Application Filing
- 2012-01-04 SI SI201230629A patent/SI2661422T1/sl unknown
- 2012-01-04 MX MX2013007837A patent/MX2013007837A/es active IP Right Grant
- 2012-01-04 MY MYPI2013701043A patent/MY162977A/en unknown
- 2012-01-04 AP AP2013007022A patent/AP3609A/xx active
- 2012-01-04 ME MEP-2016-99A patent/ME02408B/me unknown
- 2012-04-01 UA UAA201309590A patent/UA104122C2/uk unknown
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2013
- 2013-06-19 CR CR20130301A patent/CR20130301A/es unknown
- 2013-06-25 CL CL2013001882A patent/CL2013001882A1/es unknown
- 2013-06-25 TN TNP2013000274A patent/TN2013000274A1/fr unknown
- 2013-07-01 IL IL227281A patent/IL227281A/en active IP Right Grant
- 2013-07-03 CO CO13156552A patent/CO6731101A2/es unknown
- 2013-07-03 NI NI201300062A patent/NI201300062A/es unknown
- 2013-07-04 ZA ZA2013/05027A patent/ZA201305027B/en unknown
- 2013-07-05 EC ECSP13012735 patent/ECSP13012735A/es unknown
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2014
- 2014-03-17 HK HK14102651.0A patent/HK1189571A1/xx not_active IP Right Cessation
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2016
- 2016-06-21 HR HRP20160713TT patent/HRP20160713T1/hr unknown
- 2016-07-11 CY CY20161100655T patent/CY1117774T1/el unknown
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