CA2519475A1 - Bicyclic anilide spirohydantoin cgrp receptor antagonists - Google Patents
Bicyclic anilide spirohydantoin cgrp receptor antagonists Download PDFInfo
- Publication number
- CA2519475A1 CA2519475A1 CA002519475A CA2519475A CA2519475A1 CA 2519475 A1 CA2519475 A1 CA 2519475A1 CA 002519475 A CA002519475 A CA 002519475A CA 2519475 A CA2519475 A CA 2519475A CA 2519475 A1 CA2519475 A1 CA 2519475A1
- Authority
- CA
- Canada
- Prior art keywords
- substituents
- unsubstituted
- substituted
- 6alkyl
- independently selected
- 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.)
- Abandoned
Links
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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members 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 to ring carbon atoms
- C07D233/72—Two oxygen atoms, e.g. hydantoin
- C07D233/76—Two oxygen atoms, e.g. hydantoin with substituted hydrocarbon radicals attached to the third ring carbon atom
-
- 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
-
- 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
-
- 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
- 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
- C07D403/14—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 three or more hetero rings
-
- 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
- C07D405/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- 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
- C07D471/02—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 system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
- C07D471/02—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 system contains two hetero rings
- C07D471/10—Spiro-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US45560903P | 2003-03-14 | 2003-03-14 | |
| US60/455,609 | 2003-03-14 | ||
| US48664203P | 2003-07-11 | 2003-07-11 | |
| US60/486,642 | 2003-07-11 | ||
| PCT/US2004/007289 WO2004082605A2 (en) | 2003-03-14 | 2004-03-10 | Bicyclic anilide spirohydantoin cgrp receptor antagonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2519475A1 true CA2519475A1 (en) | 2004-09-30 |
Family
ID=33032696
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002519475A Abandoned CA2519475A1 (en) | 2003-03-14 | 2004-03-10 | Bicyclic anilide spirohydantoin cgrp receptor antagonists |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US7202251B2 (enExample) |
| EP (1) | EP1608627B1 (enExample) |
| JP (1) | JP4673294B2 (enExample) |
| AT (1) | ATE394400T1 (enExample) |
| AU (1) | AU2004222383B2 (enExample) |
| CA (1) | CA2519475A1 (enExample) |
| DE (1) | DE602004013563D1 (enExample) |
| WO (1) | WO2004082605A2 (enExample) |
Families Citing this family (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7842808B2 (en) | 2002-06-05 | 2010-11-30 | Bristol-Myers Squibb Company | Anti-migraine spirocycles |
| US7220862B2 (en) | 2002-06-05 | 2007-05-22 | Bristol-Myers Squibb Company | Calcitonin gene related peptide receptor antagonists |
| JP4584914B2 (ja) * | 2003-03-14 | 2010-11-24 | メルク・シャープ・エンド・ドーム・コーポレイション | ベノジアゼピンスピロヒダントインcgrp受容体拮抗物質 |
| US7189722B2 (en) * | 2003-03-14 | 2007-03-13 | Merck & Co., Inc. | Aryl spirohydantoin CGRP receptor antagonists |
| TW200508197A (en) * | 2003-03-31 | 2005-03-01 | Ucb Sa | Indolone-acetamide derivatives, processes for preparing them and their uses |
| US7569578B2 (en) | 2003-12-05 | 2009-08-04 | Bristol-Meyers Squibb Company | Heterocyclic anti-migraine agents |
| TW200533398A (en) | 2004-03-29 | 2005-10-16 | Bristol Myers Squibb Co | Novel therapeutic agents for the treatment of migraine |
| CN101014602B (zh) * | 2004-09-08 | 2011-08-10 | 默沙东公司 | 单环酰苯胺螺环内酰胺cgrp受体拮抗剂 |
| WO2006031513A2 (en) | 2004-09-09 | 2006-03-23 | Merck & Co., Inc. | Aryl spirolactam cgrp receptor antagonists |
| CN101076527B (zh) * | 2004-09-13 | 2011-11-30 | 默沙东公司 | 三环酰苯胺螺乙内酰脲cgrp受体拮抗剂 |
| JP2008512481A (ja) | 2004-09-13 | 2008-04-24 | メルク エンド カムパニー インコーポレーテッド | 二環式アニリドスピロラクタムcgrp受容体拮抗薬 |
| US7384930B2 (en) | 2004-11-03 | 2008-06-10 | Bristol-Myers Squibb Company | Constrained compounds as CGRP-receptor antagonists |
| US7384931B2 (en) | 2004-11-03 | 2008-06-10 | Bristol-Myers Squibb Company | Constrained compounds as CGRP-receptor antagonists |
| US7449586B2 (en) | 2004-12-03 | 2008-11-11 | Bristol-Myers Squibb Company | Processes for the preparation of CGRP-receptor antagonists and intermediates thereof |
| US7834007B2 (en) | 2005-08-25 | 2010-11-16 | Bristol-Myers Squibb Company | CGRP antagonists |
| DK3045182T3 (en) | 2005-11-14 | 2018-03-19 | Teva Pharmaceuticals Int Gmbh | ANTAGONIST ANTIBODIES AGAINST CALCITONIN GEN-RELATED PEPTIDE TO TREAT HEAT |
| CA2629454A1 (en) * | 2005-11-18 | 2007-05-31 | Merck & Co., Inc. | Bicyclic spirohydantoin cgrp receptor antagonists |
| US8071770B2 (en) | 2005-11-18 | 2011-12-06 | Merck Sharp & Dohme Corp. | Spirohydantoin aryl CGRP receptor antagonists |
| EP1951042B1 (en) | 2005-11-18 | 2012-10-10 | Merck Sharp & Dohme Corp. | Spirolactam tricyclic cgrp receptor antagonists |
| CA2629421A1 (en) * | 2005-11-18 | 2007-05-31 | Merck & Co., Inc. | Spirohydantoin tricyclic cgrp receptor antagonists |
| US8071772B2 (en) | 2005-11-18 | 2011-12-06 | Merck Sharp & Dohme Corp. | Spirolactam bicyclic CGRP receptor antagonists |
| EP1954135B1 (en) * | 2005-11-18 | 2012-10-10 | Merck Sharp & Dohme Corp. | Spirolactam aryl cgrp receptor antagonists |
| CN101443323A (zh) | 2006-05-09 | 2009-05-27 | 默克公司 | 取代的螺环cgrp受体拮抗剂 |
| EP2049532B1 (en) * | 2006-07-21 | 2010-06-02 | Vertex Pharmaceuticals, Inc. | Cgrp receptor antagonists |
| US7951795B2 (en) * | 2006-12-08 | 2011-05-31 | Merck Sharp & Dohme Corp. | Constrained spirocyclic compounds as CGRP receptor antagonists |
| US8148390B2 (en) | 2007-03-12 | 2012-04-03 | Merck, Sharp & Dohme, Corp. | Monocyclic anilide spirolactam CGRP receptor antagonists |
| GB0706914D0 (en) | 2007-04-10 | 2007-05-16 | Isis Innovation | Novel adenovirus vectors |
| CA2683581A1 (en) * | 2007-04-11 | 2008-10-23 | Merck & Co., Inc. | Cgrp receptor antagonists with tertiary amide, sulfonamide, carbamate and urea end groups |
| AU2008241488A1 (en) | 2007-04-16 | 2008-10-30 | Merck Sharp & Dohme Corp. | Bicyclic anilide heterocyclic CGRP receptor antagonists |
| US8143266B2 (en) | 2007-04-16 | 2012-03-27 | Merck, Sharp & Dohme Corp | Aryl heterocyclic CGRP receptor antagonists |
| WO2008147697A1 (en) | 2007-05-22 | 2008-12-04 | Boehringer Ingelheim International Gmbh | Benzimidazolone chymase inhibitors |
| ES2504565T3 (es) * | 2007-06-05 | 2014-10-08 | Merck Sharp & Dohme Corp. | Antagonistas del receptor CGRP de carboxamida heterocíclica |
| EP2166842A4 (en) * | 2007-06-07 | 2012-01-25 | Merck Sharp & Dohme | TRICYCLIC ANILIDHETEROCYCLES AS CGRP RECEPTOR ANTAGONISTS |
| WO2009109911A1 (en) | 2008-03-04 | 2009-09-11 | Pfizer Limited | Methods of treating chronic pain |
| CA2735821A1 (en) * | 2008-09-08 | 2010-03-11 | Merck Sharp & Dohme Corp. | Monocyclic amide cgrp receptor antagonists |
| WO2010033421A1 (en) * | 2008-09-18 | 2010-03-25 | Merck Sharp & Dohme Corp. | Bicyclic dihydroimidazolone cgrp receptor antagonists |
| AU2009302712A1 (en) * | 2008-10-10 | 2010-04-15 | Merck Sharp & Dohme Corp. | CGRP receptor antagonists |
| JP2012512248A (ja) * | 2008-12-17 | 2012-05-31 | メルク・シャープ・エンド・ドーム・コーポレイション | Cgrp受容体アンタゴニストとしてのイミダゾリノン誘導体 |
| IN2012DN02521A (enExample) | 2009-08-28 | 2015-08-28 | Rinat Neuroscience Corp | |
| TR201904088T4 (tr) | 2011-05-20 | 2019-05-21 | Alderbio Holdings Llc | Anti-CGRP bileşimleri ve bunların kullanımları. |
| BR112013029951B1 (pt) | 2011-05-20 | 2020-10-20 | Alderbio Holdings Llc | composição farmacêutica e uso de anticorpos ou fragmentos de anticorpos anti-cgrp para tratar ou prevenir formas de diarreia crônicas e agudas |
| AU2012258980B8 (en) | 2011-05-20 | 2017-06-15 | H. Lundbeck A/S | Use of anti-CGRP antibodies and antibody fragments to prevent or inhibit photophobia or light aversion in subjects in need thereof, especially migraine sufferers |
| AR095883A1 (es) | 2013-04-18 | 2015-11-18 | Astellas Pharma Inc | Compuestos de acetamida heterocíclica |
| US20170114122A1 (en) | 2015-10-23 | 2017-04-27 | Alderbio Holdings Llc | Regulation of glucose metabolism using anti-cgrp antibodies |
| US9896502B2 (en) | 2014-03-21 | 2018-02-20 | Teva Pharmaceuticals International Gmbh | Antagonist antibodies directed against calcitonin gene-related peptide and methods using same |
| US10556945B2 (en) | 2014-03-21 | 2020-02-11 | Teva Pharmaceuticals International Gmbh | Antagonist antibodies directed against calcitonin gene-related peptide and methods using same |
| GB201519195D0 (en) * | 2015-10-30 | 2015-12-16 | Heptares Therapeutics Ltd | CGRP Receptor Antagonists |
| JP6990657B2 (ja) * | 2016-02-08 | 2022-01-13 | エフ・ホフマン-ラ・ロシュ・アクチェンゲゼルシャフト | Ddr1阻害剤としてのスピロインドリノン |
| WO2018055574A1 (en) | 2016-09-23 | 2018-03-29 | Teva Pharmaceuticals International Gmbh | Treating refractory migraine |
| EP3366286A1 (en) | 2017-02-22 | 2018-08-29 | Johannes Keller | Compounds for treating sepsis |
| MA54704A (fr) | 2019-01-08 | 2022-04-13 | H Lundbeck As | Traitement aigu et traitement rapide de maux de tête à l'aide d'anticorps anti-cgrp |
| SG10202003296VA (en) | 2020-04-06 | 2021-11-29 | H Lundbeck As | Treatment of most bothersome symptom (mbs) associated with migraine using anti-cgrp antibodies |
| CN113402467B (zh) * | 2021-06-18 | 2022-05-13 | 山东汇海医药化工有限公司 | 一种氟班色林的合成方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4772632A (en) * | 1987-02-24 | 1988-09-20 | The United States Of America As Represented By The Department Of Health And Human Services | Antineoplastic, system - L specific amino acid nitrogen mustards |
| AUPN449295A0 (en) | 1995-07-28 | 1995-08-24 | Inner And Eastern Health Care Network, The | Radioprotectors |
| JP3449084B2 (ja) * | 1995-12-25 | 2003-09-22 | 富士レビオ株式会社 | ヒダントイン誘導体 |
| EP1606264B1 (en) * | 2003-03-14 | 2012-05-02 | Merck Sharp & Dohme Corp. | Monocyclic anilide spirohydantoin cgrp receptor antagonists |
-
2004
- 2004-03-10 AT AT04719222T patent/ATE394400T1/de not_active IP Right Cessation
- 2004-03-10 US US10/549,338 patent/US7202251B2/en not_active Expired - Lifetime
- 2004-03-10 DE DE602004013563T patent/DE602004013563D1/de not_active Expired - Lifetime
- 2004-03-10 CA CA002519475A patent/CA2519475A1/en not_active Abandoned
- 2004-03-10 AU AU2004222383A patent/AU2004222383B2/en not_active Ceased
- 2004-03-10 JP JP2006507033A patent/JP4673294B2/ja not_active Expired - Fee Related
- 2004-03-10 EP EP04719222A patent/EP1608627B1/en not_active Expired - Lifetime
- 2004-03-10 WO PCT/US2004/007289 patent/WO2004082605A2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| EP1608627B1 (en) | 2008-05-07 |
| DE602004013563D1 (de) | 2008-06-19 |
| US7202251B2 (en) | 2007-04-10 |
| AU2004222383A1 (en) | 2004-09-30 |
| US20060211712A1 (en) | 2006-09-21 |
| EP1608627A4 (en) | 2007-08-01 |
| EP1608627A2 (en) | 2005-12-28 |
| AU2004222383B2 (en) | 2009-10-01 |
| ATE394400T1 (de) | 2008-05-15 |
| WO2004082605A2 (en) | 2004-09-30 |
| WO2004082605A3 (en) | 2004-11-18 |
| JP4673294B2 (ja) | 2011-04-20 |
| JP2006520383A (ja) | 2006-09-07 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20121102 |