GB0812648D0 - Compounds - Google Patents
CompoundsInfo
- Publication number
- GB0812648D0 GB0812648D0 GBGB0812648.4A GB0812648A GB0812648D0 GB 0812648 D0 GB0812648 D0 GB 0812648D0 GB 0812648 A GB0812648 A GB 0812648A GB 0812648 D0 GB0812648 D0 GB 0812648D0
- Authority
- GB
- United Kingdom
- Prior art keywords
- compounds
- 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.)
- Ceased
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
- C07D401/02—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
-
- 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
-
- 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
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
- A61P3/06—Antihyperlipidemics
-
- 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
-
- 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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/205—Radicals derived from carbonic acid
-
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- 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
- C07D413/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Cardiology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Heart & Thoracic Surgery (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0812648.4A GB0812648D0 (en) | 2008-07-10 | 2008-07-10 | Compounds |
| EP09785308A EP2328867A1 (en) | 2008-07-10 | 2009-07-10 | Heterocyclic gpcr agonists |
| PCT/GB2009/050830 WO2010004347A1 (en) | 2008-07-10 | 2009-07-10 | Heterocyclic gpcr agonists |
| CN2009801269489A CN102131778A (zh) | 2008-07-10 | 2009-07-10 | 杂环gpcr激动剂 |
| JP2011517248A JP2011527334A (ja) | 2008-07-10 | 2009-07-10 | ヘテロ環式ｇｐｃｒ作動薬 |
| US13/003,571 US20110212939A1 (en) | 2008-07-10 | 2009-07-10 | Heterocyclic GPCR Agonists |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0812648.4A GB0812648D0 (en) | 2008-07-10 | 2008-07-10 | Compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB0812648D0 true GB0812648D0 (en) | 2008-08-20 |
Family
ID=39722073
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GBGB0812648.4A Ceased GB0812648D0 (en) | 2008-07-10 | 2008-07-10 | Compounds |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US20110212939A1 (https=) |
| EP (1) | EP2328867A1 (https=) |
| JP (1) | JP2011527334A (https=) |
| CN (1) | CN102131778A (https=) |
| GB (1) | GB0812648D0 (https=) |
| WO (1) | WO2010004347A1 (https=) |
Families Citing this family (54)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110230507A1 (en) * | 2008-07-10 | 2011-09-22 | Prosidion Limited | Piperidine GPCR Agonists |
| GB0904285D0 (en) | 2009-03-12 | 2009-04-22 | Prosidion Ltd | Compounds for the treatment of metabolic disorders |
| GB0904284D0 (en) | 2009-03-12 | 2009-04-22 | Prosidion Ltd | Compounds for the treatment of metabolic disorders |
| GB0904287D0 (en) | 2009-03-12 | 2009-04-22 | Prosidion Ltd | Compounds for the treatment of metabolic disorders |
| WO2010114907A1 (en) | 2009-03-31 | 2010-10-07 | Vanderbilt University | Sulfonyl-azetidin-3-yl-methylamine amide analogs as glyt1 inhibitors, methods for making same, and use of same in treating psychiatric disorders |
| AR077214A1 (es) | 2009-06-24 | 2011-08-10 | Neurocrine Biosciences Inc | Heterociclos nitrogenados y composiciones farmaceuticas que los contienen |
| AU2010264720A1 (en) | 2009-06-24 | 2011-12-08 | Boehringer Ingelheim International Gmbh | New compounds, pharmaceutical composition and methods relating thereto |
| EP2547339A1 (en) | 2010-03-18 | 2013-01-23 | Boehringer Ingelheim International GmbH | Combination of a gpr119 agonist and the dpp-iv inhibitor linagliptin for use in the treatment of diabetes and related conditions |
| GB201006167D0 (en) | 2010-04-14 | 2010-05-26 | Prosidion Ltd | Compounds for the treatment of metabolic disorders |
| GB201006166D0 (en) | 2010-04-14 | 2010-05-26 | Prosidion Ltd | Compounds for the treatment of metabolic disorders |
| GB2488360A (en) * | 2011-02-25 | 2012-08-29 | Prosidion Ltd | Heterocyclic GPCR agonists |
| TW201209054A (en) | 2010-05-28 | 2012-03-01 | Prosidion Ltd | Novel compounds |
| ITMI20100984A1 (it) * | 2010-05-31 | 2011-12-01 | Dipharma Francis Srl | Procedimento per la preparazione di ossadiazoli |
| 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 |
| 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 |
| TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
| WO2012066077A1 (en) | 2010-11-18 | 2012-05-24 | Prosidion Limited | 1,4 di substituted pyrrolidine - 3 - yl -amine derivatives and their use for the treatment of metabolic disorders |
| GB201114389D0 (en) | 2011-08-22 | 2011-10-05 | Prosidion Ltd | Novel compounds |
| JP5935154B2 (ja) * | 2011-03-14 | 2016-06-15 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｇｐｒ１１９モジュレーターとしてのｎ−シクロプロピル−ｎ−ピペリジニルベンズアミド |
| US8957062B2 (en) | 2011-04-08 | 2015-02-17 | Merck Sharp & Dohme Corp. | Substituted cyclopropyl compounds, compositions containing such compounds and methods of treatment |
| JP6094578B2 (ja) | 2011-06-09 | 2017-03-15 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 代謝性障害の治療のためのｇｐｒ１１９モジュレーターとしての置換ピペリジン |
| CA2836487A1 (en) | 2011-06-09 | 2012-12-13 | Rhizen Pharmaceuticals Sa | Novel compounds as modulators of gpr-119 |
| EP2720544B1 (en) | 2011-06-16 | 2016-12-21 | Merck Sharp & Dohme Corp. | Substituted cyclopropyl compounds, compositions containing such compounds, and methods of treatment |
| 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 |
| WO2013045413A1 (en) | 2011-09-27 | 2013-04-04 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| EP2760855B1 (en) | 2011-09-30 | 2017-03-15 | Merck Sharp & Dohme Corp. | Substituted cyclopropyl compounds, compositions containing such compounds as well as their use in treating type-2 diabetes |
| EP2771000B1 (en) | 2011-10-24 | 2016-05-04 | Merck Sharp & Dohme Corp. | Substituted piperidinyl compounds useful as gpr119 agonists |
| WO2013074388A1 (en) * | 2011-11-15 | 2013-05-23 | Merck Sharp & Dohme Corp. | Substituted cyclopropyl compounds useful as gpr119 agonists |
| GB2498976A (en) * | 2012-02-01 | 2013-08-07 | Prosidion Ltd | GPR119 agonists useful in the treatment of type II diabetes |
| HK1210825A1 (en) | 2012-07-11 | 2016-05-06 | Elcelyx Therapeutics, Inc. | Compositions comprising statins, biguanides and further agents for reducing cardiometabolic risk |
| KR20150118158A (ko) | 2013-02-22 | 2015-10-21 | 머크 샤프 앤드 돔 코포레이션 | 항당뇨병 비시클릭 화합물 |
| WO2014184104A1 (en) | 2013-05-17 | 2014-11-20 | Boehringer Ingelheim International Gmbh | Pyrrolidine derivatives, pharmaceutical compositions and uses thereof |
| CA2914525C (en) | 2013-06-28 | 2021-07-27 | Evotec International Gmbh | Sulfoximine substituted quinazolines for pharmaceutical compositions |
| KR101984281B1 (ko) * | 2013-08-08 | 2019-05-31 | 동아에스티 주식회사 | Gpr119 작용 활성을 갖는 신규 화합물, 이의 제조방법 및 이를 유효성분으로 함유하는 약제학적 조성물 |
| EP3068768B1 (en) | 2013-11-15 | 2019-07-31 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| WO2015176267A1 (en) | 2014-05-22 | 2015-11-26 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| WO2016022446A1 (en) | 2014-08-08 | 2016-02-11 | Merck Sharp & Dohme Corp. | [5,6]-fused bicyclic antidiabetic compounds |
| US10662171B2 (en) | 2014-08-08 | 2020-05-26 | Merck Sharp & Dohme Corp. | Antidiabetic bicyclic compounds |
| WO2016022742A1 (en) | 2014-08-08 | 2016-02-11 | Merck Sharp & Dohme Corp. | Antidiabetic bicyclic compounds |
| WO2016019587A1 (en) | 2014-08-08 | 2016-02-11 | Merck Sharp & Dohme Corp. | [7, 6]-fused bicyclic antidiabetic compounds |
| TWI687409B (zh) * | 2014-08-28 | 2020-03-11 | 日商大塚製藥股份有限公司 | 稠合雜環化合物 |
| KR101726819B1 (ko) * | 2014-10-27 | 2017-04-13 | 동아에스티 주식회사 | Gpr119 작용 활성을 갖는 화합물, 이의 제조방법 및 이를 유효성분으로 함유하는 약제학적 조성물 |
| WO2016068453A1 (en) * | 2014-10-27 | 2016-05-06 | Dong-A St Co., Ltd. | Compound having gpr119 agonistic activity, method for preparing the same, and pharmaceutical composition including the same as effective component |
| JP6976691B2 (ja) * | 2016-02-10 | 2021-12-08 | 大塚製薬株式会社 | 医薬組成物 |
| US10676458B2 (en) | 2016-03-29 | 2020-06-09 | Merch Sharp & Dohne Corp. Rahway | Antidiabetic bicyclic compounds |
| US11072602B2 (en) | 2016-12-06 | 2021-07-27 | Merck Sharp & Dohme Corp. | Antidiabetic heterocyclic compounds |
| EP3558298B1 (en) | 2016-12-20 | 2026-03-11 | Merck Sharp & Dohme LLC | Antidiabetic spirochroman compounds |
| US11225471B2 (en) | 2017-11-16 | 2022-01-18 | Merck Sharp & Dohme Corp. | Antidiabetic bicyclic compounds |
| HUE071580T2 (hu) | 2018-09-12 | 2025-09-28 | Dong A St Co Ltd | Hatóanyagként GPR119 ligandumot tartalmazó gyógyszerkészítmény nem alkoholos zsírmájbetegség megelõzésében vagy kezelésében történõ alkalmazásra |
| CA3121202A1 (en) | 2018-11-30 | 2020-06-04 | Nuvation Bio Inc. | Pyrrole and pyrazole compounds and methods of use thereof |
| KR20220150270A (ko) * | 2019-10-07 | 2022-11-10 | 칼리오페, 인크. | Gpr119 효능제 |
| TW202140440A (zh) | 2020-02-28 | 2021-11-01 | 美商克力歐普股份有限公司 | Gpr40激動劑 |
| EP4320129A1 (en) * | 2021-04-06 | 2024-02-14 | Kallyope, Inc. | Gpr119 agonists |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE188379T1 (de) * | 1992-10-14 | 2000-01-15 | Merck & Co Inc | Fibrinogenrezeptor-antagonisten |
| US6100042A (en) * | 1993-03-31 | 2000-08-08 | Cadus Pharmaceutical Corporation | Yeast cells engineered to produce pheromone system protein surrogates, and uses therefor |
| US6518423B1 (en) * | 1996-08-09 | 2003-02-11 | Eisai Co., Ltd. | Benzopiperidine derivatives |
| US6221660B1 (en) * | 1999-02-22 | 2001-04-24 | Synaptic Pharmaceutical Corporation | DNA encoding SNORF25 receptor |
| AR043057A1 (es) * | 2002-10-30 | 2005-07-13 | Vertex Pharma | Compuestos derivados de piridintiazoles como inhibidores de la quinasa rock y otras proteinas quinasa |
| CA2536253A1 (en) * | 2003-08-20 | 2005-03-03 | Vertex Pharmaceuticals Incorporated | Aminofurazan compounds useful as protein kinase inhibitors |
| AR049333A1 (es) * | 2004-04-02 | 2006-07-19 | Vertex Pharma | Azaindoles inhibidores de proteinquinasas rock y otras proteinas quinasas. composiciones farmaceuticas. |
| WO2005105780A2 (en) * | 2004-04-28 | 2005-11-10 | Vertex Pharmaceuticals Incorporated | Compositions useful as inhibitors of rock and other protein kinases |
| MX2007016508A (es) * | 2005-06-30 | 2008-03-04 | Prosidion Ltd | Agonistas del receptor acoplado a la proteina g. |
| PE20081659A1 (es) * | 2007-01-04 | 2008-10-24 | Prosidion Ltd | Agonistas de gpcr |
| US20100048632A1 (en) * | 2007-01-04 | 2010-02-25 | Matthew Colin Thor Fyfe | Piperidine GPCR Agonists |
| GB0700122D0 (en) * | 2007-01-04 | 2007-02-14 | Prosidion Ltd | GPCR agonists |
| PE20081849A1 (es) * | 2007-01-04 | 2009-01-26 | Prosidion Ltd | Derivados de piperidin-4-il-propoxi-benzamida como agonistas de gpcr |
| US20100048625A1 (en) * | 2007-01-04 | 2010-02-25 | Matthew Colin Thor Fyfe | Piperidine gpcr agonists |
-
2008
- 2008-07-10 GB GBGB0812648.4A patent/GB0812648D0/en not_active Ceased
-
2009
- 2009-07-10 CN CN2009801269489A patent/CN102131778A/zh active Pending
- 2009-07-10 WO PCT/GB2009/050830 patent/WO2010004347A1/en not_active Ceased
- 2009-07-10 US US13/003,571 patent/US20110212939A1/en not_active Abandoned
- 2009-07-10 EP EP09785308A patent/EP2328867A1/en not_active Withdrawn
- 2009-07-10 JP JP2011517248A patent/JP2011527334A/ja not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| WO2010004347A1 (en) | 2010-01-14 |
| EP2328867A1 (en) | 2011-06-08 |
| JP2011527334A (ja) | 2011-10-27 |
| CN102131778A (zh) | 2011-07-20 |
| US20110212939A1 (en) | 2011-09-01 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AT | Applications terminated before publication under section 16(1) |