EA201290840A1 - Антагонисты ванилоидного рецептора trpv1 с бициклической частью - Google Patents
Антагонисты ванилоидного рецептора trpv1 с бициклической частьюInfo
- Publication number
- EA201290840A1 EA201290840A1 EA201290840A EA201290840A EA201290840A1 EA 201290840 A1 EA201290840 A1 EA 201290840A1 EA 201290840 A EA201290840 A EA 201290840A EA 201290840 A EA201290840 A EA 201290840A EA 201290840 A1 EA201290840 A1 EA 201290840A1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- antagonists
- trpv1
- receptor trpv1
- bicyclic part
- vaniloid receptor
- Prior art date
Links
- 102000003566 TRPV1 Human genes 0.000 title abstract 3
- 101150016206 Trpv1 gene Proteins 0.000 title abstract 3
- 239000005557 antagonist Substances 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 abstract 2
- 102000011040 TRPV Cation Channels Human genes 0.000 abstract 1
- 108010062740 TRPV Cation Channels Proteins 0.000 abstract 1
- 239000004480 active ingredient Substances 0.000 abstract 1
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/26—Oxygen atoms
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/34—Oxygen atoms in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/58—Benzoxazoles; Hydrogenated benzoxazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/34—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
- C07D265/36—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings condensed with one six-membered ring
-
- 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
- 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
-
- 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
- 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
- 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Ophthalmology & Optometry (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Dermatology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
В изобретении раскрыты соединения формулы (I)где Y представляет группу формул А, В, С, D или Еи W, Q, n, R, R, R, U-U, J и K имеют значения, данные в описании. Соединения формулы (I) являются антагонистами TRPV1 и полезны в качестве активных ингредиентов фармацевтических композиций при лечении боли и других состояний, улучшаемых при ингибировании ванилоидного рецептора TRPV1.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP10158292A EP2377850A1 (en) | 2010-03-30 | 2010-03-30 | TRPV1 vanilloid receptor antagonists with a bicyclic portion |
PCT/EP2010/070538 WO2011120604A1 (en) | 2010-03-30 | 2010-12-22 | "trpv1 vanilloid receptor antagonists with a bicyclic portion" |
Publications (1)
Publication Number | Publication Date |
---|---|
EA201290840A1 true EA201290840A1 (ru) | 2013-04-30 |
Family
ID=42320777
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EA201290840A EA201290840A1 (ru) | 2010-03-30 | 2010-12-22 | Антагонисты ванилоидного рецептора trpv1 с бициклической частью |
Country Status (11)
Country | Link |
---|---|
US (3) | US9216975B2 (ru) |
EP (2) | EP2377850A1 (ru) |
JP (1) | JP5927174B2 (ru) |
KR (1) | KR20130065634A (ru) |
CN (1) | CN102858742B (ru) |
BR (1) | BR112012024712A2 (ru) |
CA (1) | CA2794773A1 (ru) |
EA (1) | EA201290840A1 (ru) |
IL (1) | IL222153A0 (ru) |
MX (1) | MX2012011244A (ru) |
WO (1) | WO2011120604A1 (ru) |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
RU2641648C1 (ru) | 2009-12-04 | 2018-01-19 | Суновион Фармасьютикалз, Инк. | Полициклические соединения и способы их применения |
AU2013355220B2 (en) * | 2012-12-06 | 2018-08-02 | Baruch S. Blumberg Institute | Functionalized benzamide derivatives as antiviral agents against HBV infection |
CN107108593B (zh) * | 2014-11-24 | 2020-03-24 | 美迪福伦Dbt有限公司 | 作为类香草素受体配体ii的基于取代的恶唑和噻唑的羧酰胺和脲衍生物 |
MA45857A (fr) | 2016-07-29 | 2021-05-19 | Sunovion Pharmaceuticals Inc | Composés et compositions, et utilisations associées |
AU2017301767A1 (en) | 2016-07-29 | 2019-02-14 | Pgi Drug Discovery Llc | Compounds and compositions and uses thereof |
JP7146782B2 (ja) | 2017-02-16 | 2022-10-04 | サノビオン ファーマシューティカルズ インク | 統合失調症を処置する方法 |
AU2018312559B2 (en) | 2017-08-02 | 2022-06-02 | Pgi Drug Discovery Llc | Isochroman compounds and uses thereof |
EA202091945A1 (ru) | 2018-02-16 | 2021-01-18 | Суновион Фармасьютикалз Инк. | Соли, кристаллические формы и способы их получения |
JP6994061B2 (ja) | 2019-02-15 | 2022-01-14 | ノバルティス アーゲー | 4-(7-ヒドロキシ-2-イソプロピル-4-オキソ-4h-キナゾリン-3-イル)-ベンゾニトリルの製剤 |
MX2021009702A (es) | 2019-02-15 | 2021-09-14 | Novartis Ag | Metodos para tratar el dolor de la superficie ocular. |
US11136304B2 (en) | 2019-03-14 | 2021-10-05 | Sunovion Pharmaceuticals Inc. | Salts of a heterocyclic compound and crystalline forms, processes for preparing, therapeutic uses, and pharmaceutical compositions thereof |
CN114585357A (zh) * | 2019-10-04 | 2022-06-03 | 千寿制药株式会社 | 含有杂环亚基乙酰胺衍生物的药物 |
CN111362878B (zh) * | 2020-03-18 | 2023-09-19 | 湖南复瑞生物医药技术有限责任公司 | 一种4-氨基-1,3-二氢-苯并咪唑-2-酮的制备方法 |
JP2023523569A (ja) | 2020-04-14 | 2023-06-06 | サノビオン ファーマシューティカルズ インク | 神経学的および精神障害の治療方法 |
KR102334947B1 (ko) | 2020-04-22 | 2021-12-06 | 주식회사 제이맥켐 | Trpv1 길항제로서 벤즈이미다졸론계 시남아마이드 유도체 및 이를 유효성분으로 함유하는 통증의 치료 또는 예방용 약학적 조성물 |
Family Cites Families (26)
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US3975531A (en) * | 1973-10-02 | 1976-08-17 | A. H. Robins Company, Incorporated | 4-(5- And 7-)benzoylindolin-2-ones and pharmaceutical uses thereof |
CH577461A5 (ru) * | 1975-08-13 | 1976-07-15 | Robins Co Inc A H | |
US4503073A (en) * | 1981-01-07 | 1985-03-05 | A. H. Robins Company, Incorporated | 2-Amino-3-(alkylthiobenzoyl)-phenylacetic acids |
US4582909A (en) * | 1984-02-02 | 1986-04-15 | Warner-Lambert Company | Benzobicyclic lactam acids and derivatives as cognition activators |
US4644005A (en) * | 1984-10-31 | 1987-02-17 | Pfizer Inc. | Oxindole antiinflammatory agents |
CO5190696A1 (es) * | 1999-06-16 | 2002-08-29 | Smithkline Beecham Corp | Antagonistas de los receptores il-8 |
EP1294688A2 (en) * | 2000-06-02 | 2003-03-26 | Sugen, Inc. | Indolinone derivatives as protein kinase/phosphatase inhibitors |
DE60208630T2 (de) | 2001-05-11 | 2006-08-17 | Pfizer Products Inc., Groton | Thiazolderivate und ihre Verwendung als cdk-Inhibitoren |
JP2003192587A (ja) * | 2001-12-26 | 2003-07-09 | Bayer Ag | 尿素誘導体 |
GB0206876D0 (en) * | 2002-03-22 | 2002-05-01 | Merck Sharp & Dohme | Therapeutic agents |
SE0302546D0 (sv) * | 2003-09-24 | 2003-09-24 | Astrazeneca Ab | New compounds |
US6933311B2 (en) * | 2003-02-11 | 2005-08-23 | Abbott Laboratories | Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor |
EP1628661A2 (en) * | 2003-06-05 | 2006-03-01 | Vertex Pharmaceuticals Incorporated | Modulators of vr1 receptor |
KR20060027338A (ko) * | 2003-06-12 | 2006-03-27 | 아스텔라스세이야쿠 가부시키가이샤 | 벤즈 아미드 유도체 또는 그 염 |
GB0322016D0 (en) * | 2003-09-19 | 2003-10-22 | Merck Sharp & Dohme | New compounds |
WO2005040100A1 (en) * | 2003-10-15 | 2005-05-06 | Bayer Healthcare Ag | Tetrahydro-naphthalene and urea derivatives |
US7683076B2 (en) * | 2003-11-08 | 2010-03-23 | Bayer Schering Pharma Aktiengesellschaft | Tetrahydro-quinolinylurea derivatives |
SE0303280D0 (sv) | 2003-12-05 | 2003-12-05 | Astrazeneca Ab | Novel compounds |
CA2563494A1 (en) * | 2004-04-20 | 2005-11-03 | Bayer Healthcare Ag | Urea derivatives as antagonists of the vanilloid receptor (vr1) |
CA2566332A1 (en) | 2004-05-14 | 2005-11-24 | Pfizer Products Inc. | Pyrimidine derivatives for the treatment of abnormal cell growth |
CA2583828A1 (en) | 2004-10-12 | 2006-04-27 | Decode Genetics, Inc. | Carboxylic acid peri-substituted bicyclics for occlusive artery disease |
US7423040B2 (en) | 2005-02-18 | 2008-09-09 | Irene Eijgendaal | Stable crystalline form of bifeprunox mesylate, dosage forms thereof and methods for using same |
CA2680173A1 (en) * | 2007-03-07 | 2008-09-12 | Alantos Pharmaceuticals Holding, Inc. | Metalloprotease inhibitors containing a heterocyclic moiety |
CL2008001003A1 (es) * | 2007-04-11 | 2008-10-17 | Actelion Pharmaceuticals Ltd | Compuestos derivados de oxazolidinona; composicion farmaceutica que comprende a dichos compuestos; y su uso para preparar un medicamento para tratar una infeccion bacteriana. |
EP2181108A2 (en) * | 2007-06-12 | 2010-05-05 | Boehringer Ingelheim International GmbH | 3-hetrocyclylidene-indolinone derivatives as inhibitors of specific cell cycle kinases |
US8969342B2 (en) | 2009-03-20 | 2015-03-03 | Brandeis University | Compounds and methods for treating mammalian gastrointestinal microbial infections |
-
2010
- 2010-03-30 EP EP10158292A patent/EP2377850A1/en not_active Withdrawn
- 2010-12-22 BR BR112012024712A patent/BR112012024712A2/pt not_active Application Discontinuation
- 2010-12-22 CN CN201080065940.9A patent/CN102858742B/zh not_active Expired - Fee Related
- 2010-12-22 EP EP10799032.7A patent/EP2552888B1/en active Active
- 2010-12-22 KR KR1020127025495A patent/KR20130065634A/ko not_active Application Discontinuation
- 2010-12-22 US US13/636,898 patent/US9216975B2/en active Active
- 2010-12-22 CA CA2794773A patent/CA2794773A1/en not_active Abandoned
- 2010-12-22 EA EA201290840A patent/EA201290840A1/ru unknown
- 2010-12-22 JP JP2013501648A patent/JP5927174B2/ja not_active Expired - Fee Related
- 2010-12-22 WO PCT/EP2010/070538 patent/WO2011120604A1/en active Application Filing
- 2010-12-22 MX MX2012011244A patent/MX2012011244A/es not_active Application Discontinuation
-
2012
- 2012-09-27 IL IL222153A patent/IL222153A0/en unknown
-
2015
- 2015-12-21 US US14/976,882 patent/US20160289199A1/en not_active Abandoned
-
2017
- 2017-02-13 US US15/431,265 patent/US10233177B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
MX2012011244A (es) | 2013-02-07 |
CN102858742A (zh) | 2013-01-02 |
CA2794773A1 (en) | 2011-10-06 |
JP5927174B2 (ja) | 2016-06-01 |
EP2552888B1 (en) | 2018-09-26 |
EP2552888A1 (en) | 2013-02-06 |
US9216975B2 (en) | 2015-12-22 |
US20170152252A1 (en) | 2017-06-01 |
KR20130065634A (ko) | 2013-06-19 |
WO2011120604A1 (en) | 2011-10-06 |
JP2013523663A (ja) | 2013-06-17 |
US10233177B2 (en) | 2019-03-19 |
US20130079339A1 (en) | 2013-03-28 |
US20160289199A1 (en) | 2016-10-06 |
IL222153A0 (en) | 2012-12-02 |
CN102858742B (zh) | 2015-05-27 |
EP2377850A1 (en) | 2011-10-19 |
BR112012024712A2 (pt) | 2016-06-07 |
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