ATE182139T1 - Dopamin rezeptor subtyp liganden - Google Patents
Dopamin rezeptor subtyp ligandenInfo
- Publication number
- ATE182139T1 ATE182139T1 AT93923608T AT93923608T ATE182139T1 AT E182139 T1 ATE182139 T1 AT E182139T1 AT 93923608 T AT93923608 T AT 93923608T AT 93923608 T AT93923608 T AT 93923608T AT E182139 T1 ATE182139 T1 AT E182139T1
- Authority
- AT
- Austria
- Prior art keywords
- pct
- dopamine receptor
- sec
- substituted
- receptor subtype
- Prior art date
Links
- 102000015554 Dopamine receptor Human genes 0.000 title abstract 2
- 108050004812 Dopamine receptor Proteins 0.000 title abstract 2
- 239000003446 ligand Substances 0.000 title abstract 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 abstract 2
- 229910052757 nitrogen Inorganic materials 0.000 abstract 2
- WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical class O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 abstract 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract 1
- 239000005864 Sulphur Substances 0.000 abstract 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract 1
- 229910052799 carbon Inorganic materials 0.000 abstract 1
- 125000004432 carbon atom Chemical group C* 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 208000035475 disorder Diseases 0.000 abstract 1
- 229960003638 dopamine Drugs 0.000 abstract 1
- 125000005842 heteroatom Chemical group 0.000 abstract 1
- 125000002950 monocyclic group Chemical group 0.000 abstract 1
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract 1
- 229910052760 oxygen Inorganic materials 0.000 abstract 1
- 239000001301 oxygen Substances 0.000 abstract 1
- 239000002243 precursor Substances 0.000 abstract 1
- 201000000980 schizophrenia Diseases 0.000 abstract 1
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
- C07D401/04—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- 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
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- 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
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/24—Antidepressants
-
- 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
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/30—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom
- C07D211/32—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom by oxygen atoms
-
- 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
- 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
- C07D403/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D409/02—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
- 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
- C07D413/04—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
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Otolaryngology (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB929222265A GB9222265D0 (en) | 1992-10-23 | 1992-10-23 | Therapeutic agents |
| GB929222263A GB9222263D0 (en) | 1992-10-23 | 1992-10-23 | Therapeutic agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ATE182139T1 true ATE182139T1 (de) | 1999-07-15 |
Family
ID=26301849
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AT93923608T ATE182139T1 (de) | 1992-10-23 | 1993-10-22 | Dopamin rezeptor subtyp liganden |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US5631269A (de) |
| EP (1) | EP0665833B1 (de) |
| JP (1) | JPH08502508A (de) |
| AT (1) | ATE182139T1 (de) |
| AU (1) | AU678186B2 (de) |
| CA (1) | CA2146019A1 (de) |
| DE (1) | DE69325662T2 (de) |
| ES (1) | ES2133416T3 (de) |
| WO (1) | WO1994010145A1 (de) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9309573D0 (en) * | 1993-05-10 | 1993-06-23 | Merck Sharp & Dohme | Therapeutic agents |
| DK124393D0 (da) * | 1993-11-03 | 1993-11-03 | Lundbeck & Co As H | Compounds |
| DE69524241T2 (de) * | 1994-09-30 | 2002-06-13 | Pfizer Inc., New York | 2,7,-substituierte octahydro-1h-pyrido[1,2-a]pyrazin derivate |
| US5668148A (en) * | 1995-04-20 | 1997-09-16 | Merck & Co., Inc. | Alpha1a adrenergic receptor antagonists |
| WO1997023482A1 (en) * | 1995-12-21 | 1997-07-03 | Pfizer Inc. | 2,7-substituted octahydro-pyrrolo[1,2-a]pyrazine derivatives |
| US6187774B1 (en) | 1996-03-04 | 2001-02-13 | Yoshitomi Pharmaceutical Industries, Ltd. | Fused heterocyclic compounds and pharmaceutical applications thereof |
| US6664258B1 (en) | 1996-08-26 | 2003-12-16 | Pfizer Inc | Spirocyclic dopamine receptor subtype ligands |
| UA52698C2 (uk) | 1996-10-04 | 2003-01-15 | Х. Луннбек А/С | Похідні (3-алкоксіізоксазол-4-іл)заміщеної 2-амінокарбонової кислоти та їх сірковмісні аналоги, фармацевтична композиція на їх основі |
| KR20050033070A (ko) * | 2002-08-09 | 2005-04-08 | 아스트라제네카 에이비이 | 메타보트로픽 글루타메이트 수용체-5의 조절제로서[1,2,4]옥사디아졸 |
| AU2003268064A1 (en) * | 2002-08-09 | 2004-02-25 | Astrazeneca Ab | Oxadiazoles as modulators of metabotropic glutamate receptor-5 |
| AU2003264018A1 (en) * | 2002-08-09 | 2004-02-25 | Astrazeneca Ab | Compounds having an activity at metabotropic glutamate receptors |
| UY30892A1 (es) * | 2007-02-07 | 2008-09-02 | Smithkline Beckman Corp | Inhibidores de la actividad akt |
| CA2687931C (en) * | 2007-05-31 | 2016-05-24 | Boehringer Ingelheim International Gmbh | Ccr2 receptor antagonists and uses thereof |
| CN102256963B (zh) | 2008-12-19 | 2014-06-11 | 贝林格尔.英格海姆国际有限公司 | 作为ccr2受体拮抗剂用于治疗炎症、哮喘和copd的环状嘧啶-4-甲酰胺 |
| MY161598A (en) * | 2009-01-30 | 2017-04-28 | Glaxosmithkline Llc | Crystalline n-{ (1s)-2-amino-1-[(3-fluorophenyl)methyl]ethyl} -5-chloro-4-(4-chloro-1-methyl-1h-pyrazol-5-yl)-2-thiophenecarboxamide hydrochloride |
| CA2764232A1 (en) * | 2009-05-07 | 2010-11-11 | Torrent Pharmaceuticals Limited | Novel heterocyclic compounds |
| MX346393B (es) | 2009-12-17 | 2017-03-17 | Centrexion Therapeutics Corp | Nuevos antagonistas del receptor ccr2 y usos de los mismo. |
| EP2568812B1 (de) * | 2010-05-11 | 2016-10-26 | Merck Sharp & Dohme Corp. | Neuartige prolylcarboxypeptidase-hemmer |
| JP2013526507A (ja) | 2010-05-12 | 2013-06-24 | 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 | 新規ccr2受容体アンタゴニスト、その製造方法及び薬物としてのその使用 |
| WO2011141477A1 (en) | 2010-05-12 | 2011-11-17 | Boehringer Ingelheim International Gmbh | New ccr2 receptor antagonists, method for producing the same, and use thereof as medicaments |
| WO2011144501A1 (en) | 2010-05-17 | 2011-11-24 | Boehringer Ingelheim International Gmbh | Ccr2 antagonists and uses thereof |
| WO2011147772A1 (en) | 2010-05-25 | 2011-12-01 | Boehringer Ingelheim International Gmbh | Ccr2 receptor antagonists |
| US8962656B2 (en) | 2010-06-01 | 2015-02-24 | Boehringer Ingelheim International Gmbh | CCR2 antagonists |
| WO2013010839A1 (en) | 2011-07-15 | 2013-01-24 | Boehringer Ingelheim International Gmbh | Novel and selective ccr2 antagonists |
| CN106255679B (zh) | 2014-02-27 | 2019-09-06 | 默克专利有限公司 | 用作nav通道抑制剂的杂环化合物及其用途 |
| US10450293B2 (en) * | 2014-05-16 | 2019-10-22 | Emory University | Chemokine CXCR4 and CCR5 receptor modulators and uses related thereto |
| DK3202766T3 (da) | 2014-10-01 | 2020-03-23 | Daiichi Sankyo Co Ltd | Isoxazolderivat som muteret isocitratdehydrogenase 1-inhibitor |
| AU2016287584B2 (en) | 2015-07-02 | 2020-03-26 | Centrexion Therapeutics Corporation | (4-((3R,4R)-3-methoxytetrahydro-pyran-4-ylamino)piperidin-1-yl)(5-methyl-6-(((2R,6S)-6-(p-tolyl)tetrahydro-2H-pyran-2-yl)methylamino)pyrimidin-4yl)methanone citrate |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU198036B (en) * | 1983-08-22 | 1989-07-28 | Hoechst Roussel Pharma | Process for production of derivatives of 3-piperidil-/1h/-indasole and medical preparatives containing them |
| GB8714789D0 (en) * | 1987-06-24 | 1987-07-29 | Lundbeck & Co As H | Heterocyclic compounds |
| IE63906B1 (en) * | 1987-11-13 | 1995-06-14 | Novo Nordisk As | Azabicyclic compounds and their preparation and use |
| US5043345A (en) * | 1989-02-22 | 1991-08-27 | Novo Nordisk A/S | Piperidine compounds and their preparation and use |
| DK0402644T3 (da) * | 1989-05-19 | 1996-01-02 | Hoechst Roussel Pharma | N-(Aryloxyalkyl)-heteroarylpiperidiner og -heteroarylpiperaziner, fremgangsmåde til deres fremstilli ng samt deres anvendelse som medikamenter |
| PT100525B (pt) * | 1991-05-29 | 1999-10-29 | Abbott Lab | Azaspiranos substituidos imunomodulares, seu uso e composicoes farmaceuticas que os contem |
-
1993
- 1993-10-22 CA CA002146019A patent/CA2146019A1/en not_active Abandoned
- 1993-10-22 JP JP6510809A patent/JPH08502508A/ja active Pending
- 1993-10-22 EP EP93923608A patent/EP0665833B1/de not_active Expired - Lifetime
- 1993-10-22 WO PCT/GB1993/002190 patent/WO1994010145A1/en not_active Ceased
- 1993-10-22 US US08/424,364 patent/US5631269A/en not_active Expired - Fee Related
- 1993-10-22 DE DE69325662T patent/DE69325662T2/de not_active Expired - Fee Related
- 1993-10-22 ES ES93923608T patent/ES2133416T3/es not_active Expired - Lifetime
- 1993-10-22 AT AT93923608T patent/ATE182139T1/de not_active IP Right Cessation
- 1993-10-22 AU AU53414/94A patent/AU678186B2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| JPH08502508A (ja) | 1996-03-19 |
| DE69325662D1 (de) | 1999-08-19 |
| WO1994010145A1 (en) | 1994-05-11 |
| EP0665833B1 (de) | 1999-07-14 |
| US5631269A (en) | 1997-05-20 |
| AU5341494A (en) | 1994-05-24 |
| CA2146019A1 (en) | 1994-05-11 |
| ES2133416T3 (es) | 1999-09-16 |
| AU678186B2 (en) | 1997-05-22 |
| EP0665833A1 (de) | 1995-08-09 |
| DE69325662T2 (de) | 2000-02-10 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| RER | Ceased as to paragraph 5 lit. 3 law introducing patent treaties |