DE60016359D1 - Verbindungen als selektive agonisten der alpha 2b oder 2b/2c adrenergische rezeptoren - Google Patents
Verbindungen als selektive agonisten der alpha 2b oder 2b/2c adrenergische rezeptorenInfo
- Publication number
- DE60016359D1 DE60016359D1 DE60016359T DE60016359T DE60016359D1 DE 60016359 D1 DE60016359 D1 DE 60016359D1 DE 60016359 T DE60016359 T DE 60016359T DE 60016359 T DE60016359 T DE 60016359T DE 60016359 D1 DE60016359 D1 DE 60016359D1
- Authority
- DE
- Germany
- Prior art keywords
- alpha
- compounds
- selective agonists
- adrenergic receptors
- lower alkyl
- 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 - Lifetime
Links
Classifications
-
- 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
- C07D233/56—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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- 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
- A61P27/06—Antiglaucoma agents or miotics
-
- 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
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/06—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring carbon atoms
- C07D233/08—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring carbon atoms with alkyl radicals, containing more than four carbon atoms, directly attached to ring carbon atoms
- C07D233/10—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring carbon atoms with alkyl radicals, containing more than four carbon atoms, directly attached to ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring nitrogen atoms
-
- 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
- C07D233/64—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 substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- 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
- C07D233/84—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
- C07D263/28—Nitrogen atoms not forming part of a nitro radical
-
- 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
- C07D401/06—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 carbon chain containing only aliphatic carbon 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
- C07D403/06—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 carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D405/06—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 carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth 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)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US32975299A | 1999-06-10 | 1999-06-10 | |
PCT/US2000/015795 WO2001000586A1 (en) | 1999-06-10 | 2000-06-08 | Compounds as selective agonists at alpha 2b or 2b/2c adrenergic receptors |
US329752 | 2002-12-27 |
Publications (2)
Publication Number | Publication Date |
---|---|
DE60016359D1 true DE60016359D1 (de) | 2005-01-05 |
DE60016359T2 DE60016359T2 (de) | 2005-12-01 |
Family
ID=23286854
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE60016359T Expired - Lifetime DE60016359T2 (de) | 1999-06-10 | 2000-06-08 | Verbindungen als selektive agonisten der alpha 2b oder 2b/2c adrenergische rezeptoren |
Country Status (11)
Country | Link |
---|---|
EP (1) | EP1104407B1 (de) |
AT (1) | ATE283843T1 (de) |
AU (1) | AU773668B2 (de) |
CZ (1) | CZ2001864A3 (de) |
DE (1) | DE60016359T2 (de) |
ES (1) | ES2228544T3 (de) |
HK (1) | HK1035724A1 (de) |
HU (1) | HUP0104390A3 (de) |
RU (1) | RU2232154C2 (de) |
TW (1) | TWI283669B (de) |
WO (1) | WO2001000586A1 (de) |
Families Citing this family (40)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6841684B2 (en) * | 1997-12-04 | 2005-01-11 | Allergan, Inc. | Imidiazoles having reduced side effects |
AU2002254265B2 (en) * | 1997-12-04 | 2008-05-15 | Allergan, Inc. | Imidiazole derivatives and their use as agonists selective at alpha 2B or 2B/2C adrenergic receptors |
US6388090B2 (en) | 2000-01-14 | 2002-05-14 | Orion Corporation | Imidazole derivatives |
FI20000073A0 (fi) * | 2000-01-14 | 2000-01-14 | Orion Yhtymae Oy | Uusia imidatsolijohdannaisia |
US6534542B2 (en) | 2001-02-27 | 2003-03-18 | Allergen Sales, Inc. | (2-hydroxy)ethyl-thioureas useful as modulators of α2B adrenergic receptors |
US7057046B2 (en) | 2002-05-20 | 2006-06-06 | Bristol-Myers Squibb Company | Lactam glycogen phosphorylase inhibitors and method of use |
US7323485B2 (en) | 2002-05-21 | 2008-01-29 | Allergan, Inc. | 4-(substituted cycloalkylmethyl) imidazole-2-thiones, 4-(substituted cycloalkenylmethyl) imidazole-2-thiones, 4-(substituted cycloalkylmethyl) imidazol-2-ones and 4-(substituted cycloalkenylmethyl) imidazol-2-ones and related compounds |
US7358269B2 (en) | 2002-05-21 | 2008-04-15 | Allergan, Inc. | 2-((2-Thioxo-2,3-dihydro-1H-imidazol-4-yl)methyl)-3,4-dihydronapthalen-1(2H)-one |
US7276522B2 (en) | 2002-05-21 | 2007-10-02 | Allergan, Inc. | 4-(substituted cycloalkylmethyl) imidazole-2-thiones, 4-(substituted cycloalkenylmethyl) imidazole-2-thiones, 4-(substituted cycloalkylmethyl) imidazol-2-ones, 4-(substituted cycloalkenylmethyl) imidazol-2-ones and related compounds |
US7345065B2 (en) * | 2002-05-21 | 2008-03-18 | Allergan, Inc. | Methods and compositions for alleviating pain |
US7091232B2 (en) | 2002-05-21 | 2006-08-15 | Allergan, Inc. | 4-(substituted cycloalkylmethyl) imidazole-2-thiones, 4-(substituted cycloalkenylmethyl) imidazole-2-thiones, 4-(substituted cycloalkylmethyl) imidazol-2-ones and 4-(substituted cycloalkenylmethyl) imidazol-2-ones and related compounds |
US7098235B2 (en) | 2002-11-14 | 2006-08-29 | Bristol-Myers Squibb Co. | Triglyceride and triglyceride-like prodrugs of glycogen phosphorylase inhibiting compounds |
WO2005039567A1 (en) * | 2003-10-08 | 2005-05-06 | Allergan, Inc. | Pharmaceutical compositions comprising alpha-2-adrenergics and trefoil factor family peptides |
ATE505470T1 (de) * | 2004-05-07 | 2011-04-15 | Memory Pharm Corp | 1h-indazole, benzothiazole, 1,2-benzisoxazole, 1, 2-benzisothiazole und chromone und deren herstellung und verwendungen |
WO2006036507A1 (en) | 2004-09-24 | 2006-04-06 | Allergan, Inc. | 4-(heteroaryl-methyl and substituted heteroaryl-methyl)-imidazole-2-thiones acting as alpha2 adrenergic agonists |
WO2006036497A2 (en) | 2004-09-24 | 2006-04-06 | Allergan, Inc. | 4-(condensed cyclicmethyl)-imidazole-2-thiones acting as alpha2 adrenergic agonists |
KR20070054213A (ko) * | 2004-09-24 | 2007-05-28 | 알러간, 인코포레이티드 | 특이적인 알파2 아드레날린성 아고니스트로서 작용하는4-(페닐메틸 및 치환된 페닐메틸)-이미다졸-2-티온 |
BRPI0516217A (pt) | 2004-09-28 | 2008-08-26 | Allergan Inc | compostos de 4-benzil-1,3-diidro-imidazol-2-tionas não-substituìdos e substituìdos que atuam como agonistas especìficos ou seletivos alfa2-adrenérgicos e métodos de utilização dos mesmos |
US7390829B2 (en) | 2005-06-29 | 2008-06-24 | Allergan, Inc. | Alpha-2 adrenergic agonists |
US8003624B2 (en) | 2005-08-25 | 2011-08-23 | Schering Corporation | Functionally selective ALPHA2C adrenoreceptor agonists |
BRPI0615307A2 (pt) * | 2005-08-25 | 2009-08-04 | Schering Corp | agonistas de adrenorreceptor alfa2c |
US7700592B2 (en) | 2005-08-25 | 2010-04-20 | Schering Corporation | α2C adrenoreceptor agonists |
EP1934203B1 (de) | 2005-08-25 | 2010-08-18 | Schering Corporation | 3,4-dihydro-2H-benzo[1,4]oxazin- und 3,4-dihydro-2H-benzo[1,4]thiazin-VERBINDUNGEN ALS ALPHA2C-ADRENOREZEPTOR-ANTAGONISTEN |
US7592362B2 (en) | 2006-01-19 | 2009-09-22 | Pfizer Limited | Substituted imidazoles |
US7323477B2 (en) * | 2006-02-02 | 2008-01-29 | Allergan, Inc. | 7-((1H-imidazol-4-yl)methyl)-5,6,7,8-tetrahydroquinoline |
BRPI0718400A2 (pt) | 2006-11-16 | 2014-03-11 | Hoffmann La Roche | 4-imidazóis substituídos |
US7868020B2 (en) | 2007-01-12 | 2011-01-11 | Allergan, Inc. | Quinolynylmethylimidizoles as therapeutic agents |
US8013169B2 (en) | 2007-01-12 | 2011-09-06 | Allergan, Inc | Naphthylmethylimidizoles as therapeutic agents |
US8119807B2 (en) | 2007-01-12 | 2012-02-21 | Allergan, Inc. | Quinolynylmethylimidizoles as therapeutic agents |
JP2010518163A (ja) | 2007-02-13 | 2010-05-27 | シェーリング コーポレイション | 機能選択性α2Cアドレナリン受容体アゴニスト |
US8470863B2 (en) | 2007-02-13 | 2013-06-25 | Merck Sharp & Dohme, Corp. | Derivatives and analogs of chroman as functionally selective ALPHA2C adrenoreceptor agonists |
MX2009008775A (es) | 2007-02-13 | 2010-03-01 | Schering Corp | Agonistas de adrenorreceptores alfa2c funcionalmente selectivos. |
DK2155715T3 (da) * | 2007-05-14 | 2013-05-13 | Allergan Inc | ((Phenyl)imidazolyl)methylheteroarylforbindelser |
BRPI0816157A2 (pt) * | 2007-08-15 | 2017-06-13 | Allergan Inc | compostos adrenérgicos |
US7902247B2 (en) * | 2008-01-09 | 2011-03-08 | Allergan, Inc. | Substituted-aryl-2-phenylethyl-1H-imidazole compounds as subtype selective modulators of alpha 2B and/or alpha 2C adrenergic receptors |
CA2712256A1 (en) | 2008-01-18 | 2009-07-23 | Allergan, Inc. | Substitued-aryl-(imidazole)-methyl)-phenyl compounds as subtype selective modulators of alpha 2b and/or alpha 2c adrenergic receptors |
US8383818B2 (en) | 2008-02-21 | 2013-02-26 | Merck Sharp & Dohme Corp. | Functionally selective alpha2C adrenoreceptor agonists |
WO2010042473A1 (en) | 2008-10-07 | 2010-04-15 | Schering Corporation | Biaryl spiroaminooxazoline analogues as alpha2c adrenergic receptor modulators |
US20120225918A1 (en) * | 2011-03-03 | 2012-09-06 | Voom, Llc | Compositions and Methods for Non-Surgical Treatment of Ptosis |
CN111372576A (zh) | 2017-11-17 | 2020-07-03 | 塞尔利克斯生物私人有限公司 | 用于治疗眼部病症的组合物和方法 |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU518569B2 (en) * | 1979-08-07 | 1981-10-08 | Farmos-Yhtyma Oy | 4-benzyl- and 4-benzoyl imidazole derivatives |
JPH01242571A (ja) * | 1988-03-22 | 1989-09-27 | Mitsui Petrochem Ind Ltd | イミダゾール誘導体の製造方法 |
GB9520150D0 (en) * | 1995-10-03 | 1995-12-06 | Orion Yhtymae Oy | New imidazole derivatives |
US5621113A (en) * | 1996-03-28 | 1997-04-15 | Ortho Pharmaceutical Corporation | 4-[(thien-2-yl)methyl]-imidazole analgesics |
US5750720A (en) * | 1996-03-28 | 1998-05-12 | Ortho Pharmaceutical Corporation | 4- (thien-3-yl)methyl!-imidazole analgesics |
WO1999018075A1 (fr) * | 1997-10-02 | 1999-04-15 | Yukijirushi Nyugyo Kabushiki Kaisha | Nouveaux composes a base de dihydronaphtalene et leur procede de production |
HUP0004557A3 (en) * | 1997-12-04 | 2002-03-28 | Allergan Inc Irvine | Substituted imidazole derivatives having agonist-like activity at alpha 2b or 2b/2c adrenergic receptors and pharmaceuticals containing the same |
-
2000
- 2000-06-07 TW TW089111068A patent/TWI283669B/zh not_active IP Right Cessation
- 2000-06-08 RU RU2001107028/04A patent/RU2232154C2/ru not_active IP Right Cessation
- 2000-06-08 AU AU54749/00A patent/AU773668B2/en not_active Ceased
- 2000-06-08 WO PCT/US2000/015795 patent/WO2001000586A1/en active IP Right Grant
- 2000-06-08 ES ES00939699T patent/ES2228544T3/es not_active Expired - Lifetime
- 2000-06-08 HU HU0104390A patent/HUP0104390A3/hu unknown
- 2000-06-08 DE DE60016359T patent/DE60016359T2/de not_active Expired - Lifetime
- 2000-06-08 CZ CZ2001864A patent/CZ2001864A3/cs unknown
- 2000-06-08 AT AT00939699T patent/ATE283843T1/de not_active IP Right Cessation
- 2000-06-08 EP EP00939699A patent/EP1104407B1/de not_active Expired - Lifetime
-
2001
- 2001-09-07 HK HK01106343A patent/HK1035724A1/xx not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
EP1104407A1 (de) | 2001-06-06 |
HUP0104390A2 (hu) | 2002-04-29 |
TWI283669B (en) | 2007-07-11 |
EP1104407B1 (de) | 2004-12-01 |
DE60016359T2 (de) | 2005-12-01 |
HK1035724A1 (en) | 2001-12-07 |
RU2232154C2 (ru) | 2004-07-10 |
HUP0104390A3 (en) | 2002-05-28 |
ES2228544T3 (es) | 2005-04-16 |
CZ2001864A3 (cs) | 2001-09-12 |
ATE283843T1 (de) | 2004-12-15 |
AU773668B2 (en) | 2004-06-03 |
AU5474900A (en) | 2001-01-31 |
WO2001000586A1 (en) | 2001-01-04 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
8364 | No opposition during term of opposition |