CA2649822C - Inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 - Google Patents
Inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 Download PDFInfo
- Publication number
- CA2649822C CA2649822C CA2649822A CA2649822A CA2649822C CA 2649822 C CA2649822 C CA 2649822C CA 2649822 A CA2649822 A CA 2649822A CA 2649822 A CA2649822 A CA 2649822A CA 2649822 C CA2649822 C CA 2649822C
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- halogens
- optionally substituted
- compound
- pharmaceutically acceptable
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired - Fee Related
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- 239000003112 inhibitor Substances 0.000 title description 15
- 102100036506 11-beta-hydroxysteroid dehydrogenase 1 Human genes 0.000 title 1
- 101710186107 11-beta-hydroxysteroid dehydrogenase 1 Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 124
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 26
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 105
- 150000002367 halogens Chemical class 0.000 claims description 84
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 37
- 150000003839 salts Chemical class 0.000 claims description 35
- 238000002360 preparation method Methods 0.000 claims description 27
- 238000011282 treatment Methods 0.000 claims description 18
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 13
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 9
- 239000000460 chlorine Substances 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 2
- HRQZDRUQNIYJCT-NRFANRHFSA-N (3r)-3-[[2,6-dichloro-4-[4-(4-hydroxypiperidine-1-carbonyl)phenyl]phenyl]methyl]-1-piperidin-1-ylpyrrolidin-2-one Chemical group C1CC(O)CCN1C(=O)C1=CC=C(C=2C=C(Cl)C(C[C@H]3C(N(N4CCCCC4)CC3)=O)=C(Cl)C=2)C=C1 HRQZDRUQNIYJCT-NRFANRHFSA-N 0.000 claims 1
- RSMPMNOURSAYDL-NRFANRHFSA-N (3r)-3-[[2,6-dichloro-4-[4-[4-(trifluoromethyl)piperidine-1-carbonyl]phenyl]phenyl]methyl]-1-piperidin-1-ylpyrrolidin-2-one Chemical group C1CC(C(F)(F)F)CCN1C(=O)C1=CC=C(C=2C=C(Cl)C(C[C@H]3C(N(N4CCCCC4)CC3)=O)=C(Cl)C=2)C=C1 RSMPMNOURSAYDL-NRFANRHFSA-N 0.000 claims 1
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- LWMPFIOTEAXAGV-UHFFFAOYSA-N piperidin-1-amine Chemical compound NN1CCCCC1 LWMPFIOTEAXAGV-UHFFFAOYSA-N 0.000 description 1
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical class O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 1
- 229960002797 pitavastatin Drugs 0.000 description 1
- VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 description 1
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- FYPMFJGVHOHGLL-UHFFFAOYSA-N probucol Chemical compound C=1C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=1SC(C)(C)SC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 FYPMFJGVHOHGLL-UHFFFAOYSA-N 0.000 description 1
- 229960003912 probucol Drugs 0.000 description 1
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- 238000011321 prophylaxis Methods 0.000 description 1
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- 102000004169 proteins and genes Human genes 0.000 description 1
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- 238000011160 research Methods 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- XMSXOLDPMGMWTH-UHFFFAOYSA-N rivoglitazone Chemical compound CN1C2=CC(OC)=CC=C2N=C1COC(C=C1)=CC=C1CC1SC(=O)NC1=O XMSXOLDPMGMWTH-UHFFFAOYSA-N 0.000 description 1
- 229960004586 rosiglitazone Drugs 0.000 description 1
- 229960000672 rosuvastatin Drugs 0.000 description 1
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
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- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
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- ZAADRXMXROEPIU-UHFFFAOYSA-N tert-butyl(2-chloropropan-2-yloxy)silane Chemical compound CC(C)(C)[SiH2]OC(C)(C)Cl ZAADRXMXROEPIU-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- 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
- C07D401/14—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 three or more hetero rings
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- General Chemical & Material Sciences (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Endocrinology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US74556506P | 2006-04-25 | 2006-04-25 | |
| US60/745,565 | 2006-04-25 | ||
| PCT/US2007/067353 WO2007127765A1 (en) | 2006-04-25 | 2007-04-25 | Inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2649822A1 CA2649822A1 (en) | 2007-11-08 |
| CA2649822C true CA2649822C (en) | 2013-08-13 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2649822A Expired - Fee Related CA2649822C (en) | 2006-04-25 | 2007-04-25 | Inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US8148534B2 (https=) |
| EP (1) | EP2016071B1 (https=) |
| JP (1) | JP5101602B2 (https=) |
| CN (1) | CN101432277B (https=) |
| AU (1) | AU2007244863B2 (https=) |
| BR (1) | BRPI0710875A2 (https=) |
| CA (1) | CA2649822C (https=) |
| EA (1) | EA016360B1 (https=) |
| ES (1) | ES2429570T3 (https=) |
| MX (1) | MX2008013656A (https=) |
| WO (1) | WO2007127765A1 (https=) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| AU2007240550B2 (en) | 2006-04-21 | 2012-02-23 | Eli Lilly And Company | Cyclohexylpyrazole-lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| ES2422165T3 (es) | 2006-04-21 | 2013-09-09 | Lilly Co Eli | Derivados de ciclohexilimidazol lactama como inhibidores de 11-beta-hidroxiesteroide deshidrogenasa 1 |
| EA014718B1 (ru) | 2006-04-21 | 2011-02-28 | Эли Лилли Энд Компани | Производные бифениламидлактама в качестве ингибиторов 11-бета-гидроксистероиддегидрогеназы 1 |
| EP2049475B1 (en) | 2006-04-24 | 2012-02-01 | Eli Lilly & Company | Cyclohexyl substituted pyrrolidinones as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| EP2021336B1 (en) * | 2006-04-24 | 2010-06-30 | Eli Lilly And Company | Inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| EA016959B1 (ru) | 2006-04-24 | 2012-08-30 | Эли Лилли Энд Компани | Замещенные пирролидиноны в качестве ингибиторов 11-бета-гидроксистероиддегидрогеназы 1 типа |
| ATE455110T1 (de) | 2006-04-25 | 2010-01-15 | Lilly Co Eli | 11-beta-hydroxysteroid-dehydrogenase-1-hemmer |
| ATE471311T1 (de) | 2006-04-25 | 2010-07-15 | Lilly Co Eli | Inhibitoren von11-beta- hydroxysteroiddehydrogenase 1 |
| CN101448816B (zh) * | 2006-04-28 | 2013-08-07 | 伊莱利利公司 | 作为11-β-羟类固醇脱氢酶1的抑制剂的哌啶基取代的吡咯烷酮类 |
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| US8507493B2 (en) | 2009-04-20 | 2013-08-13 | Abbvie Inc. | Amide and amidine derivatives and uses thereof |
| WO2011068927A2 (en) * | 2009-12-04 | 2011-06-09 | Abbott Laboratories | 11-β-HYDROXYSTEROID DEHYDROGENASE TYPE 1 (11B-HSD1) INHIBITORS AND USES THEREOF |
| WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| WO2011157827A1 (de) | 2010-06-18 | 2011-12-22 | Sanofi | Azolopyridin-3-on-derivate als inhibitoren von lipasen und phospholipasen |
| US8530413B2 (en) | 2010-06-21 | 2013-09-10 | Sanofi | Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments |
| TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
| TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
| TW201215387A (en) | 2010-07-05 | 2012-04-16 | Sanofi Aventis | Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament |
| US8871758B2 (en) | 2011-03-08 | 2014-10-28 | Sanofi | Tetrasubstituted oxathiazine derivatives, method for producing them, their use as medicine and drug containing said derivatives and the use thereof |
| EP2683705B1 (de) | 2011-03-08 | 2015-04-22 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| US8828995B2 (en) | 2011-03-08 | 2014-09-09 | Sanofi | Branched oxathiazine derivatives, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof |
| WO2012120052A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| EP2683699B1 (de) | 2011-03-08 | 2015-06-24 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| WO2013037390A1 (en) | 2011-09-12 | 2013-03-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| EP2760862B1 (en) | 2011-09-27 | 2015-10-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| EP3880655A1 (en) * | 2018-11-16 | 2021-09-22 | Bristol-Myers Squibb Company | Synthetic processes for the production of 1-((3s,4r)-4-(2,6-difluoro-4-methoxyphenyl)-2-oxopyrrolidin-3-yl)-3-phenylurea |
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| WO2004056744A1 (en) | 2002-12-23 | 2004-07-08 | Janssen Pharmaceutica N.V. | Adamantyl acetamides as hydroxysteroid dehydrogenase inhibitors |
| NZ551076A (en) * | 2004-05-07 | 2009-05-31 | Janssen Pharmaceutica Nv | Adamantyl pyrrolidin-2-one derivatives as 11-beta hydroxysteroid dehydrogenase inhibitors |
| NZ551077A (en) | 2004-05-07 | 2009-05-31 | Janssen Pharmaceutica Nv | Pyrrolidin-2-one and piperidin-2-one derivatives as 11-beta hydroxysteroid dehydrogenase inhibitors |
| WO2006040329A1 (en) | 2004-10-12 | 2006-04-20 | Novo Nordisk A/S | 1 ibeta- hydroxysteroid dehydrogenase type 1 active spiro compounds |
| US7713979B2 (en) | 2004-10-29 | 2010-05-11 | Eli Lilly And Company | Cycloalkyl lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| CA2585797C (en) | 2004-11-10 | 2015-01-06 | Incyte Corporation | Lactam compounds and their use as pharmaceuticals |
| ATE399546T1 (de) | 2004-12-20 | 2008-07-15 | Lilly Co Eli | Cycloalkyl-lactam-derivate als inhibitoren von 11-beta-hydroxysteroiddehydrogenase 1 |
| ATE401073T1 (de) | 2004-12-21 | 2008-08-15 | Lilly Co Eli | Cycloalkyl-lactam-derivate als inhibitoren von 11-beta-hydroxysteroiddehydrogenase 1 |
| US20090264650A1 (en) | 2005-03-31 | 2009-10-22 | Nobuo Cho | Prophylactic/Therapeutic Agent for Diabetes |
| WO2007084314A2 (en) | 2006-01-12 | 2007-07-26 | Incyte Corporation | MODULATORS OF 11-ß HYDROXYL STEROID DEHYDROGENASE TYPE 1, PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS OF USING THE SAME |
| AU2007240550B2 (en) | 2006-04-21 | 2012-02-23 | Eli Lilly And Company | Cyclohexylpyrazole-lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| ES2422165T3 (es) | 2006-04-21 | 2013-09-09 | Lilly Co Eli | Derivados de ciclohexilimidazol lactama como inhibidores de 11-beta-hidroxiesteroide deshidrogenasa 1 |
| EA014718B1 (ru) * | 2006-04-21 | 2011-02-28 | Эли Лилли Энд Компани | Производные бифениламидлактама в качестве ингибиторов 11-бета-гидроксистероиддегидрогеназы 1 |
| EP2021336B1 (en) | 2006-04-24 | 2010-06-30 | Eli Lilly And Company | Inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| EA016959B1 (ru) * | 2006-04-24 | 2012-08-30 | Эли Лилли Энд Компани | Замещенные пирролидиноны в качестве ингибиторов 11-бета-гидроксистероиддегидрогеназы 1 типа |
| EP2049475B1 (en) | 2006-04-24 | 2012-02-01 | Eli Lilly & Company | Cyclohexyl substituted pyrrolidinones as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| ATE471311T1 (de) | 2006-04-25 | 2010-07-15 | Lilly Co Eli | Inhibitoren von11-beta- hydroxysteroiddehydrogenase 1 |
| ATE455110T1 (de) | 2006-04-25 | 2010-01-15 | Lilly Co Eli | 11-beta-hydroxysteroid-dehydrogenase-1-hemmer |
| CN101448816B (zh) | 2006-04-28 | 2013-08-07 | 伊莱利利公司 | 作为11-β-羟类固醇脱氢酶1的抑制剂的哌啶基取代的吡咯烷酮类 |
| CL2008001839A1 (es) | 2007-06-21 | 2009-01-16 | Incyte Holdings Corp | Compuestos derivados de 2,7-diazaespirociclos, inhibidores de 11-beta hidroxil esteroide deshidrogenasa tipo 1; composicion farmaceutica que comprende a dichos compuestos; utiles para tratar la obesidad, diabetes, intolerancia a la glucosa, diabetes tipo ii, entre otras enfermedades. |
| WO2011068927A2 (en) * | 2009-12-04 | 2011-06-09 | Abbott Laboratories | 11-β-HYDROXYSTEROID DEHYDROGENASE TYPE 1 (11B-HSD1) INHIBITORS AND USES THEREOF |
-
2007
- 2007-04-25 ES ES07761237T patent/ES2429570T3/es active Active
- 2007-04-25 JP JP2009507937A patent/JP5101602B2/ja not_active Expired - Fee Related
- 2007-04-25 CA CA2649822A patent/CA2649822C/en not_active Expired - Fee Related
- 2007-04-25 EP EP07761237.2A patent/EP2016071B1/en not_active Not-in-force
- 2007-04-25 US US12/297,910 patent/US8148534B2/en not_active Expired - Fee Related
- 2007-04-25 WO PCT/US2007/067353 patent/WO2007127765A1/en not_active Ceased
- 2007-04-25 MX MX2008013656A patent/MX2008013656A/es active IP Right Grant
- 2007-04-25 BR BRPI0710875-3A patent/BRPI0710875A2/pt not_active IP Right Cessation
- 2007-04-25 CN CN200780014900XA patent/CN101432277B/zh not_active Expired - Fee Related
- 2007-04-25 AU AU2007244863A patent/AU2007244863B2/en not_active Ceased
- 2007-04-25 EA EA200870476A patent/EA016360B1/ru not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| CA2649822A1 (en) | 2007-11-08 |
| WO2007127765A1 (en) | 2007-11-08 |
| AU2007244863B2 (en) | 2012-01-19 |
| AU2007244863A1 (en) | 2007-11-08 |
| CN101432277A (zh) | 2009-05-13 |
| JP5101602B2 (ja) | 2012-12-19 |
| CN101432277B (zh) | 2013-12-25 |
| US8148534B2 (en) | 2012-04-03 |
| US20090275613A1 (en) | 2009-11-05 |
| EA016360B1 (ru) | 2012-04-30 |
| EP2016071B1 (en) | 2013-07-24 |
| JP2009535358A (ja) | 2009-10-01 |
| MX2008013656A (es) | 2008-11-10 |
| ES2429570T3 (es) | 2013-11-15 |
| EP2016071A1 (en) | 2009-01-21 |
| BRPI0710875A2 (pt) | 2012-01-10 |
| EA200870476A1 (ru) | 2009-04-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20190425 |