IL114784A - Benzoxazolyl-and benzothiazolyloxa-zolidinones stheir preparation and pharmaceutical compositions containing them - Google Patents
Benzoxazolyl-and benzothiazolyloxa-zolidinones stheir preparation and pharmaceutical compositions containing themInfo
- Publication number
- IL114784A IL114784A IL11478495A IL11478495A IL114784A IL 114784 A IL114784 A IL 114784A IL 11478495 A IL11478495 A IL 11478495A IL 11478495 A IL11478495 A IL 11478495A IL 114784 A IL114784 A IL 114784A
- Authority
- IL
- Israel
- Prior art keywords
- alkyl
- substd
- opt
- alkoxy
- acyl
- Prior art date
Links
Classifications
-
- 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
- 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
-
- 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
- A61K31/42—Oxazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- 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
- C07D417/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4427475 | 1994-08-03 | ||
| DE19514313A DE19514313A1 (de) | 1994-08-03 | 1995-04-18 | Benzoxazolyl- und Benzothiazolyloxazolidinone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL114784A0 IL114784A0 (en) | 1995-11-27 |
| IL114784A true IL114784A (en) | 1999-10-28 |
Family
ID=25938925
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL11478495A IL114784A (en) | 1994-08-03 | 1995-07-31 | Benzoxazolyl-and benzothiazolyloxa-zolidinones stheir preparation and pharmaceutical compositions containing them |
Country Status (30)
| Country | Link |
|---|---|
| US (1) | US5529998A (ro) |
| EP (1) | EP0697412B1 (ro) |
| JP (1) | JPH0881463A (ro) |
| KR (1) | KR960007585A (ro) |
| CN (1) | CN1122803A (ro) |
| AT (1) | ATE188698T1 (ro) |
| AU (1) | AU698939B2 (ro) |
| BG (1) | BG62404B1 (ro) |
| CA (1) | CA2155092A1 (ro) |
| CO (1) | CO4410392A1 (ro) |
| CZ (1) | CZ198895A3 (ro) |
| DE (2) | DE19514313A1 (ro) |
| DZ (1) | DZ1920A1 (ro) |
| EE (1) | EE9500049A (ro) |
| FI (1) | FI953665L (ro) |
| HR (1) | HRP950428A2 (ro) |
| HU (1) | HUT75037A (ro) |
| IL (1) | IL114784A (ro) |
| MA (1) | MA23638A1 (ro) |
| NO (1) | NO305701B1 (ro) |
| NZ (1) | NZ272674A (ro) |
| PE (1) | PE2796A1 (ro) |
| PL (1) | PL309848A1 (ro) |
| RO (1) | RO115263B1 (ro) |
| SK (1) | SK97495A3 (ro) |
| SV (1) | SV1995000045A (ro) |
| TN (1) | TNSN95088A1 (ro) |
| TW (1) | TW352386B (ro) |
| YU (1) | YU51095A (ro) |
| ZA (1) | ZA956445B (ro) |
Families Citing this family (60)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HRP960159A2 (en) * | 1995-04-21 | 1997-08-31 | Bayer Ag | Benzocyclopentane oxazolidinones containing heteroatoms |
| GB9601666D0 (en) * | 1996-01-27 | 1996-03-27 | Zeneca Ltd | Chemical compounds |
| DE19604223A1 (de) * | 1996-02-06 | 1997-08-07 | Bayer Ag | Neue substituierte Oxazolidinone |
| HRP970049A2 (en) * | 1996-02-06 | 1998-04-30 | Bayer Ag | New heteroaryl oxazolidinones |
| GB9702213D0 (en) | 1996-02-24 | 1997-03-26 | Zeneca Ltd | Chemical compounds |
| GB9609919D0 (en) * | 1996-05-11 | 1996-07-17 | Zeneca Ltd | Chemical compounds |
| GB9717804D0 (en) | 1997-08-22 | 1997-10-29 | Zeneca Ltd | Chemical compounds |
| GB9717807D0 (en) * | 1997-08-22 | 1997-10-29 | Zeneca Ltd | Chemical compounds |
| GB9725244D0 (en) | 1997-11-29 | 1998-01-28 | Zeneca Ltd | Chemical compounds |
| WO1999037630A1 (en) | 1998-01-23 | 1999-07-29 | Versicor, Inc. | Oxazolidinone combinatorial libraries, compositions and methods of preparation |
| WO1999064417A2 (en) * | 1998-06-05 | 1999-12-16 | Astrazeneca Ab | Oxazolidinone derivatives, process for their preparation and pharmaceutical compositions containing them |
| GB9815880D0 (en) | 1998-07-21 | 1998-09-16 | Pfizer Ltd | Heterocycles |
| US6420349B1 (en) | 1998-08-24 | 2002-07-16 | Bristol-Myers Squibb Company | Isoxazolinone antibacterial agents |
| WO2000029409A1 (de) * | 1998-11-17 | 2000-05-25 | Bayer Aktiengesellschaft | Neue heterocyclyl-substituierte oxazolidon-derivate |
| EP1147422A1 (en) | 1999-01-27 | 2001-10-24 | Pharmacia & Upjohn Company | Assays for modulators of "elongation factor p" activity |
| GB9928568D0 (en) | 1999-12-03 | 2000-02-02 | Zeneca Ltd | Chemical compounds |
| US6514529B2 (en) | 2000-03-22 | 2003-02-04 | Pharmacia & Upjohn Company | Oxazolidinone tablet formulation |
| MY127336A (en) * | 2000-03-22 | 2006-11-30 | Upjohn Co | Container for linezolid iv solution |
| GB0009803D0 (en) * | 2000-04-25 | 2000-06-07 | Astrazeneca Ab | Chemical compounds |
| US6465456B2 (en) | 2000-06-29 | 2002-10-15 | Bristol-Myers Squibb Company | Isoxazolinone antibacterial agents |
| DE60112581T2 (de) | 2000-06-30 | 2006-06-01 | Pharmacia & Upjohn Co. Llc, Kalamazoo | Zusammensetzungen zur Behandlung bakterieller Infektionen, welche ein Oxazolidinonderivat, Sulbactam und Ampicillin enthalten |
| KR100944645B1 (ko) | 2000-12-15 | 2010-03-04 | 버텍스 파마슈티칼스 인코포레이티드 | 자이라제 억제제 및 이를 포함하는 약제학적 조성물 |
| CA2424402A1 (en) | 2000-12-21 | 2002-08-01 | Pharmacia & Upjohn Company | Antimicrobial quinolone derivatives and use of the same to treat bacterial infections |
| US7141588B2 (en) * | 2002-02-25 | 2006-11-28 | Pfizer, Inc. | N-aryl-2-oxazolidinone-5-carboxamides and their derivatives |
| AR038536A1 (es) * | 2002-02-25 | 2005-01-19 | Upjohn Co | N-aril-2-oxazolidinona-5- carboxamidas y sus derivados |
| US20030216330A1 (en) * | 2002-03-29 | 2003-11-20 | Pharmacia & Upjohn | Parenteral, intravenous, and oral administration of oxazolidinones for treating diabetic foot infections |
| US7727992B2 (en) * | 2002-06-13 | 2010-06-01 | Vertex Pharmaceuticals Incorporated | Gyrase inhibitors and uses thereof |
| ES2258234T3 (es) * | 2002-08-12 | 2006-08-16 | PHARMACIA & UPJOHN COMPANY LLC | N-aril-2-oxazolidinonas y sus derivados. |
| AU2002339721A1 (en) * | 2002-09-20 | 2004-04-08 | Lupin Limited | Oxazolidinone derivatives, process for their preperation and their use as antimycobacterial agents |
| US7141570B2 (en) * | 2002-11-21 | 2006-11-28 | Pharmacia & Upjohn Company | N-aryl-2-oxazolidinone-5-carboxamides and their derivatives |
| US7582635B2 (en) | 2002-12-24 | 2009-09-01 | Purdue Pharma, L.P. | Therapeutic agents useful for treating pain |
| US7569591B2 (en) * | 2003-01-31 | 2009-08-04 | Vertex Pharmaceuticals Incorporated | Gyrase inhibitors and uses thereof |
| US7618974B2 (en) * | 2003-01-31 | 2009-11-17 | Vertex Pharmaceuticals Incorporated | Gyrase inhibitors and uses thereof |
| US7582641B2 (en) * | 2003-01-31 | 2009-09-01 | Vertex Pharmaceuticals Incorporated | Gyrase inhibitors and uses thereof |
| AR042956A1 (es) | 2003-01-31 | 2005-07-13 | Vertex Pharma | Inhibidores de girasa y usos de los mismos |
| US8193352B2 (en) * | 2003-01-31 | 2012-06-05 | Vertex Pharmaceuticals Incorporated | Gyrase inhibitors and uses thereof |
| JP2006516989A (ja) * | 2003-02-07 | 2006-07-13 | ワーナー−ランバート・カンパニー、リミテッド、ライアビリティ、カンパニー | 抗菌剤として使用するための二環式環によりn−置換されたオキサゾリジノン誘導体 |
| CA2515311A1 (en) * | 2003-02-07 | 2004-08-19 | Warner-Lambert Company Llc | Antibacterial agents |
| US7012088B2 (en) * | 2003-02-24 | 2006-03-14 | Pharmacia & Upjohn Company | Indolone oxazolidinones and derivatives thereof |
| US20040204463A1 (en) * | 2003-04-01 | 2004-10-14 | Harris Christina Renee | N-aryl-2-oxazolidinone-5-carboxamides and their derivatives |
| CA2536480A1 (en) * | 2003-08-25 | 2005-03-03 | Warner-Lambert Company Llc | Novel antimicrobial aryloxazolidinone compounds |
| US7304050B2 (en) * | 2003-09-16 | 2007-12-04 | Pfizer Inc. | Antibacterial agents |
| US20060004090A1 (en) * | 2004-07-01 | 2006-01-05 | Roberts William J | Forskolin compositions and methods for administration |
| EP2032565A2 (en) * | 2006-02-01 | 2009-03-11 | Pfizer Products Inc. | Benzisoxazole oxazolidinones as antibacterial agents |
| CN103497173A (zh) | 2006-03-31 | 2014-01-08 | 财团法人乙卯研究所 | 具有杂环的新化合物 |
| AU2008246202B2 (en) * | 2007-04-27 | 2011-12-01 | Purdue Pharma L.P. | Therapeutic agents useful for treating pain |
| US20090170867A1 (en) * | 2007-04-27 | 2009-07-02 | Shionogi & Co., Ltd. | Trpv1 antagonists including sulfonamide substituent and uses thereof |
| JPWO2009044777A1 (ja) | 2007-10-02 | 2011-02-10 | 財団法人乙卯研究所 | 7員ヘテロ環を有するオキサゾリジノン誘導体 |
| CA2713187C (en) * | 2008-02-22 | 2016-06-07 | Actelion Pharmaceuticals Ltd | Oxazolidinone derivatives |
| US8759362B2 (en) * | 2008-10-24 | 2014-06-24 | Purdue Pharma L.P. | Bicycloheteroaryl compounds and their use as TRPV1 ligands |
| US8703962B2 (en) * | 2008-10-24 | 2014-04-22 | Purdue Pharma L.P. | Monocyclic compounds and their use as TRPV1 ligands |
| EP2663557B1 (en) | 2011-01-14 | 2015-05-27 | Vertex Pharmaceuticals Incorporated | Pyrimidine gyrase and topoisomerase iv inhibitors |
| EP2663556B1 (en) | 2011-01-14 | 2014-10-15 | Vertex Pharmaceuticals Incorporated | Process of making gyrase and topoisomerase iv inhibitors |
| KR101897950B1 (ko) | 2011-01-14 | 2018-09-12 | 스페로 트리넴, 인코포레이티드 | 자이라제 억제제 (r)1에틸3[5[2{1하이드록시1메틸에틸}피리미딘5일]7(테트라하이드로푸란2일}1h벤즈이미다졸2일]우레아의 고체 형태 |
| US8476281B2 (en) | 2011-01-14 | 2013-07-02 | Vertex Pharmaceuticals Incorporated | Solid forms of gyrase inhibitor (R)-1-ethyl-3-[6-fluoro-5-[2-(1-hydroxy-1-methyl-ethyl)pyrimidin-5-yl]-7-(tetrahydrofuran-2-yl)-1H-benzimidazol-2-yl]urea |
| TWI554515B (zh) | 2011-06-20 | 2016-10-21 | 維泰克斯製藥公司 | 旋轉酶(gyrase)及拓樸異構酶抑制劑之磷酸酯 |
| RU2621708C2 (ru) | 2011-06-22 | 2017-06-07 | ПУРДЬЮ ФАРМА Эл. Пи. | Антагонисты trpv1, включающие дигидроксигруппу в качестве заместителя, и их применение |
| US9394293B2 (en) | 2011-08-10 | 2016-07-19 | Purdue Pharma L.P. | TRPV1 antagonists including dihydroxy substituent and uses thereof |
| TWI595002B (zh) | 2012-07-18 | 2017-08-11 | 思沛羅三南公司 | (R)-2-(5-(2-(3-乙基脲基)-6-氟-7-(四氫呋喃-2-基)-1H-苯并[d]咪唑-5-基)嘧啶-2-基)丙烷-2-基磷酸二氫鹽之固體形式及其鹽 |
| WO2014014845A1 (en) | 2012-07-18 | 2014-01-23 | Vertex Pharmaceuticals Incorporated | Combination therapy comprising|1 -ethyl-3-[5-[2-{1 -hydroxy-1 -methyl-ethyl}pyrimidin-5-yl]-7-(tetra hydrofuran-2-|yl}-1 h-benzimidazol-2-yl]urea and derivatives thereof to treat mycobacterium|diseases |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4705799A (en) | 1983-06-07 | 1987-11-10 | E. I. Du Pont De Nemours And Company | Aminomethyl oxooxazolidinyl benzenes useful as antibacterial agents |
| GB8504871D0 (en) * | 1985-02-26 | 1985-03-27 | Ici Plc | Heterocyclic compounds |
| US4921869A (en) | 1987-10-09 | 1990-05-01 | E. I. Du Pont De Nemours And Company | Aminomethyl oxooxazolidinyl cycloalkylbenzene derivatives useful as antibacterial agents |
| US4801600A (en) | 1987-10-09 | 1989-01-31 | E. I. Du Pont De Nemours And Company | Aminomethyl oxooxazolidinyl cycloalkylbenzene derivatives useful as antibacterial agents |
| US4965268A (en) | 1987-10-09 | 1990-10-23 | E. I. Du Pont De Nemours And Company | Aminomethyl oxooxazolidinyl cycloalkylbenzene derivatives useful as antibacterial agents |
| CA1320730C (en) | 1987-10-16 | 1993-07-27 | The Du Pont Merck Pharmaceutical Company | Aminomethyl oxooxazolidinyl aroylbenzene derivatives useful as antibacterial agents |
| US5254577A (en) | 1988-07-29 | 1993-10-19 | The Du Pont Merck Pharmaceutical Company | Aminomethyloxooxazolidinyl arylbenzene derivatives useful as antibacterial agents |
| DE68918792T2 (de) * | 1988-09-15 | 1995-03-30 | Upjohn Co | 5-Indolinyl-5-beta-amidomethyloxazolidin-2-one, 3-(substituierte kondensierte)phenyl-5-beta amidomethyloxazolidin-2-one und 3-(Nitrogen-substituierte)phenyl-5-beta-amidomethyloxazolidin-2-one. |
| JP2669579B2 (ja) | 1991-10-23 | 1997-10-29 | エーザイ株式会社 | オキサゾリドン誘導体 |
| CA2119556C (en) * | 1991-11-01 | 2004-07-06 | Michael Robert Barbachyn | Substituted aryl- and heteroaryl-phenyloxazolidinones |
-
1995
- 1995-04-18 DE DE19514313A patent/DE19514313A1/de not_active Withdrawn
- 1995-06-14 TN TNTNSN95088A patent/TNSN95088A1/fr unknown
- 1995-07-18 RO RO95-01322A patent/RO115263B1/ro unknown
- 1995-07-21 DE DE59507595T patent/DE59507595D1/de not_active Expired - Fee Related
- 1995-07-21 EP EP95111477A patent/EP0697412B1/de not_active Expired - Lifetime
- 1995-07-21 AT AT95111477T patent/ATE188698T1/de active
- 1995-07-25 HR HR19514313.2A patent/HRP950428A2/hr not_active Application Discontinuation
- 1995-07-27 AU AU27230/95A patent/AU698939B2/en not_active Ceased
- 1995-07-27 US US08/508,245 patent/US5529998A/en not_active Expired - Fee Related
- 1995-07-28 JP JP7211265A patent/JPH0881463A/ja active Pending
- 1995-07-28 NZ NZ272674A patent/NZ272674A/en unknown
- 1995-07-28 SV SV1995000045A patent/SV1995000045A/es unknown
- 1995-07-31 IL IL11478495A patent/IL114784A/xx active IP Right Grant
- 1995-07-31 CA CA002155092A patent/CA2155092A1/en not_active Abandoned
- 1995-08-01 PL PL95309848A patent/PL309848A1/xx unknown
- 1995-08-01 FI FI953665A patent/FI953665L/fi unknown
- 1995-08-01 BG BG99833A patent/BG62404B1/bg unknown
- 1995-08-02 KR KR1019950023799A patent/KR960007585A/ko not_active Withdrawn
- 1995-08-02 DZ DZ950098A patent/DZ1920A1/fr active
- 1995-08-02 HU HU9502295A patent/HUT75037A/hu unknown
- 1995-08-02 ZA ZA956445A patent/ZA956445B/xx unknown
- 1995-08-02 EE EE9500049A patent/EE9500049A/xx unknown
- 1995-08-02 CZ CZ951988A patent/CZ198895A3/cs unknown
- 1995-08-02 PE PE1995275165A patent/PE2796A1/es not_active Application Discontinuation
- 1995-08-02 SK SK974-95A patent/SK97495A3/sk unknown
- 1995-08-02 NO NO953045A patent/NO305701B1/no unknown
- 1995-08-03 MA MA23979A patent/MA23638A1/fr unknown
- 1995-08-03 CN CN95115330A patent/CN1122803A/zh active Pending
- 1995-08-03 CO CO95034777A patent/CO4410392A1/es unknown
- 1995-08-03 TW TW084108069A patent/TW352386B/zh active
- 1995-08-11 YU YU51095A patent/YU51095A/sh unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| KB | Patent renewed |