ATE377592T1 - Neurotropische substituierte pyrimidine - Google Patents
Neurotropische substituierte pyrimidineInfo
- Publication number
- ATE377592T1 ATE377592T1 AT00923138T AT00923138T ATE377592T1 AT E377592 T1 ATE377592 T1 AT E377592T1 AT 00923138 T AT00923138 T AT 00923138T AT 00923138 T AT00923138 T AT 00923138T AT E377592 T1 ATE377592 T1 AT E377592T1
- Authority
- AT
- Austria
- Prior art keywords
- substituted pyrimidines
- neurotropic
- neurodegenerative
- therapy
- contain
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
- C07D239/49—Two nitrogen atoms with an aralkyl radical, or substituted aralkyl radical, attached in position 5, e.g. trimethoprim
-
- 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
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/288,495 US6583148B1 (en) | 1999-04-08 | 1999-04-08 | Neurotrophic substituted pyrimidines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ATE377592T1 true ATE377592T1 (de) | 2007-11-15 |
Family
ID=23107364
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AT00923138T ATE377592T1 (de) | 1999-04-08 | 2000-04-06 | Neurotropische substituierte pyrimidine |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US6583148B1 (de) |
| EP (1) | EP1165523B1 (de) |
| JP (1) | JP4743463B2 (de) |
| AT (1) | ATE377592T1 (de) |
| AU (1) | AU4331400A (de) |
| CA (1) | CA2368843C (de) |
| DE (1) | DE60037013T2 (de) |
| WO (1) | WO2000061562A1 (de) |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE60142236D1 (de) * | 2000-07-24 | 2010-07-08 | Krenitsky Pharmaceuticals Inc | Substituierte 5-alkinyl-pyrimidine mit neurotropher wirkung |
| PL371678A1 (en) * | 2002-02-13 | 2005-06-27 | F.Hoffmann-La Roche Ag | Novel pyridin- and pyrimidin-derivatives |
| JP2005232081A (ja) * | 2004-02-19 | 2005-09-02 | Bayer Cropscience Ag | ベンジルピリミジン誘導体の農園芸用殺菌剤としての利用 |
| PL1725540T3 (pl) | 2004-03-05 | 2013-02-28 | Hoffmann La Roche | Diaminopirymidyny jako antagoniści p2x3 i p2x2/3 |
| US20110230479A1 (en) * | 2005-04-15 | 2011-09-22 | Longo Frank M | Neurotrophin mimetics and uses thereof |
| EP2586445A1 (de) * | 2005-04-15 | 2013-05-01 | University Of North Carolina At Chapel Hill | Verfahren zur Ermöglichung des Überlebens von Nervenzellen mit Neurotrophin-Mimetika |
| EP1893192A4 (de) | 2005-06-08 | 2010-03-31 | Univ North Carolina | Verfahren zur ermöglichung des überlebens von nervenzellen anhand nicht-peptidischer und peptidscher bdnf-neurotrophin-mimetika |
| JP4850913B2 (ja) | 2005-09-01 | 2012-01-11 | エフ．ホフマン−ラ ロシュ アーゲー | Ｐ２ｘ３及びｐ２ｘ２／３調節因子としてのジアミノピリジン |
| ES2612890T3 (es) * | 2005-09-01 | 2017-05-19 | F. Hoffmann-La Roche Ag | Diaminopirimidinas como moduladores de P2X3 y P2X2/3 |
| AU2006286601B2 (en) * | 2005-09-01 | 2012-07-05 | F. Hoffmann-La Roche Ag | Diaminopyrimidines as P2X3 and P2X2/3 modulators |
| BRPI0615613A2 (pt) * | 2005-09-01 | 2009-05-19 | Hoffmann La Roche | diaminopirimidinas como moduladores de p2x3 e p3x2/3 |
| RU2433119C2 (ru) * | 2006-04-28 | 2011-11-10 | Шионоги Энд Ко., Лтд. | Производное амина, обладающее антагонистической активностью в отношении рецептора npy y5 |
| AU2007244358B2 (en) | 2006-04-28 | 2012-06-14 | Shionogi & Co., Ltd. | Amine derivative having NPY Y5 receptor antagonist activity |
| ZA200809146B (en) * | 2006-04-28 | 2009-12-30 | Shionogi & Co | Amine derivative having NPY Y5 receptor antagonist activity |
| SA08290668B1 (ar) | 2007-10-25 | 2012-02-12 | شيونوجي آند كو.، ليمتد | مشتقات أمين لها نشاط مضاد لمستقبل npy y5 واستخداماتها |
| US8227618B2 (en) | 2009-04-23 | 2012-07-24 | Shionogi & Co., Ltd. | Amine-derivatives having NPY Y5 receptor antagonistic activity and the uses thereof |
| US10273219B2 (en) | 2009-11-12 | 2019-04-30 | Pharmatrophix, Inc. | Crystalline forms of neurotrophin mimetic compounds and their salts |
| WO2011060262A1 (en) | 2009-11-12 | 2011-05-19 | Pharmatrophix, Inc. | Crystalline forms of neurotrophin mimetic compounds and their salts |
| SI3590928T1 (sl) * | 2011-04-08 | 2021-10-29 | Janssen Sciences Ireland Unlimited Co | Derivati pirimidina za zdravljenje virusnih okužb |
| EA036645B1 (ru) | 2011-11-09 | 2020-12-03 | Янссен Сайенсиз Айрлэнд Юси | Производные пурина для лечения вирусных инфекций |
| MY167797A (en) | 2012-07-13 | 2018-09-26 | Janssen Sciences Ireland Uc | Macrocyclic purines for the treatment of viral infections |
| CN104781239B (zh) * | 2012-08-10 | 2019-03-01 | 爱尔兰詹森科学公司 | 用于治疗病毒感染和另外的疾病的烷基嘧啶衍生物 |
| EP2906563B1 (de) | 2012-10-10 | 2018-02-28 | Janssen Sciences Ireland UC | Pyrrolo[3,2-d]pyrimidin-derivate zur behandlung von virusinfektionen und anderen erkrankungen |
| AU2013346793B2 (en) | 2012-11-16 | 2018-03-08 | Janssen Sciences Ireland Uc | Heterocyclic substituted 2-amino-quinazoline derivatives for the treatment of viral infections |
| KR102300861B1 (ko) * | 2013-02-21 | 2021-09-10 | 얀센 사이언시즈 아일랜드 언리미티드 컴퍼니 | 바이러스 감염의 치료를 위한 2-아미노피리미딘 유도체 |
| AU2014228017B2 (en) | 2013-03-15 | 2018-08-30 | Pharmatrophix, Inc. | Non-peptide BDNF Neurotrophin mimetics |
| JP2016516044A (ja) | 2013-03-15 | 2016-06-02 | ファーマトロフィックス， インコーポレイテッド | 非ペプチドｂｄｎｆニューロトロフィン模倣化合物 |
| HRP20170654T1 (hr) | 2013-03-29 | 2017-06-30 | Janssen Sciences Ireland Uc | Makrociklički deaza-purinoni za liječenje virusnih infekcija |
| WO2014187932A1 (en) | 2013-05-24 | 2014-11-27 | Janssen R&D Ireland | Pyridone derivatives for the treatment of viral infections and further diseases |
| CA2913028C (en) | 2013-06-27 | 2022-03-08 | Janssen Sciences Ireland Uc | Pyrrolo[3,2-d]pyrimidine derivatives for the treatment of viral infections and other diseases |
| JP6401788B2 (ja) | 2013-07-30 | 2018-10-10 | ヤンセン・サイエンシズ・アイルランド・ユーシー | ウイルス感染治療用チエノ［３，２−ｄ］ピリミジン誘導体 |
| WO2018002319A1 (en) | 2016-07-01 | 2018-01-04 | Janssen Sciences Ireland Uc | Dihydropyranopyrimidines for the treatment of viral infections |
| US10968184B2 (en) | 2016-09-29 | 2021-04-06 | Janssen Sciences Ireland Unlimited Company | Pyrimidine prodrugs for the treatment of viral infections and further diseases |
| TW202415645A (zh) | 2018-03-01 | 2024-04-16 | 愛爾蘭商健生科學愛爾蘭無限公司 | ２，４－二胺基喹唑啉衍生物及其醫學用途 |
| EA202190623A1 (ru) | 2018-08-27 | 2021-05-21 | Сумитомо Дайниппон Фарма Ко., Лтд. | Оптически активное азабициклическое производное |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2691655A (en) | 1952-05-24 | 1954-10-12 | Burroughs Wellcome Co | 2-amino-4-substituted amino-6-aryl pyrimidines and process of preparing same |
| GB951431A (en) | 1959-03-17 | 1964-03-04 | Wellcome Found | Pyrimidine derivatives and the manufacture thereof |
| US3862190A (en) | 1972-09-08 | 1975-01-21 | Pfizer | 5-(unsubstituted and substituted phenoxy)-4-amino pyrimidines |
| DK397574A (de) * | 1973-08-24 | 1975-04-28 | Ciba Geigy Ag | |
| GB1523274A (en) | 1974-08-05 | 1978-08-31 | Ici Ltd | Herbicidal compositions containing substituted pyrimidine |
| FR2358148A1 (fr) | 1976-07-12 | 1978-02-10 | Dick Pr | Derives de 2,4-diaminopyrimidines et leur mise en solution en association avec des sulfamides |
| FR2397407A2 (fr) | 1977-07-11 | 1979-02-09 | Dick Pierre | Derives de 2,4-diamino pyrimidines et leur mise en solution en association avec des sulfamides |
| FI895821A7 (fi) | 1988-12-07 | 1990-06-08 | The Wellcome Foundation Ltd | Farmaseuttisesti aktivisia CNS-yhdisteitä |
| GB9012316D0 (en) | 1990-06-01 | 1990-07-18 | Wellcome Found | Pharmacologically active cns compounds |
| IE912114A1 (en) | 1990-07-02 | 1992-01-15 | Union Pharma Scient Appl | Novel pyrimidine derivatives which are angiotensin ii¹receptor antagonists, their methods of preparation and¹pharmaceutical compositions in which they are present |
| US5075305A (en) | 1991-03-18 | 1991-12-24 | Warner-Lambert Company | Compound, composition and use |
| BR9205906A (pt) | 1991-04-17 | 1994-07-05 | Pfizer | Derivados de pirimidina para aumento da atividade antitumoral |
| US5336677A (en) | 1991-10-24 | 1994-08-09 | American Home Products Corporation | Substituted aminopyrimidines as antihypertensives |
| GB9125842D0 (en) | 1991-12-04 | 1992-02-05 | Ici Plc | Heterocyclic derivatives |
| AU5704594A (en) | 1992-12-18 | 1994-07-19 | Wellcome Foundation Limited, The | Pyrimidine, pyridine, pteridinone and indazole derivatives as enzyme inhibitors |
| DE69408750T2 (de) | 1993-08-26 | 1998-07-23 | Ono Pharmaceutical Co | 4-Aminopyrimidin Derivate |
| JPH08283246A (ja) | 1994-06-01 | 1996-10-29 | Nippon Soda Co Ltd | ピリミジン誘導体、その製造方法及び有害生物防除剤 |
| EP0826674A4 (de) | 1995-04-03 | 1998-07-08 | Sumitomo Pharma | Als psychotrope drogen wirksame pyrimidinderivate und verfahren zu deren herstellung |
| US6440965B1 (en) | 1997-10-15 | 2002-08-27 | Krenitsky Pharmaceuticals, Inc. | Substituted pyrimidine derivatives, their preparation and their use in the treatment of neurodegenerative or neurological disorders of the central nervous system |
-
1999
- 1999-04-08 US US09/288,495 patent/US6583148B1/en not_active Expired - Fee Related
-
2000
- 2000-04-06 US US09/958,511 patent/US6916820B1/en not_active Expired - Fee Related
- 2000-04-06 CA CA002368843A patent/CA2368843C/en not_active Expired - Fee Related
- 2000-04-06 AT AT00923138T patent/ATE377592T1/de not_active IP Right Cessation
- 2000-04-06 AU AU43314/00A patent/AU4331400A/en not_active Abandoned
- 2000-04-06 JP JP2000610837A patent/JP4743463B2/ja not_active Expired - Fee Related
- 2000-04-06 EP EP00923138A patent/EP1165523B1/de not_active Expired - Lifetime
- 2000-04-06 WO PCT/US2000/009108 patent/WO2000061562A1/en not_active Ceased
- 2000-04-06 DE DE60037013T patent/DE60037013T2/de not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| EP1165523A1 (de) | 2002-01-02 |
| JP4743463B2 (ja) | 2011-08-10 |
| JP2002541245A (ja) | 2002-12-03 |
| CA2368843C (en) | 2009-10-20 |
| WO2000061562A1 (en) | 2000-10-19 |
| DE60037013T2 (de) | 2008-08-21 |
| US6916820B1 (en) | 2005-07-12 |
| AU4331400A (en) | 2000-11-14 |
| US6583148B1 (en) | 2003-06-24 |
| DE60037013D1 (de) | 2007-12-20 |
| EP1165523B1 (de) | 2007-11-07 |
| CA2368843A1 (en) | 2000-10-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ATE377592T1 (de) | Neurotropische substituierte pyrimidine | |
| DK1303495T3 (da) | Substituerede 5-alkylnylpyrimidiner med neurotrofisk aktivitet | |
| TW200500344A (en) | Novel compounds | |
| EA200701296A1 (ru) | 3,5-дизамещенные и 3,5,7-тризамещенные 3h-оксазоло- и 3h-тиазоло[4,5-d] пиримидин-2-оны и их пролекарства | |
| AU9693998A (en) | Substituted pyrimidine derivatives, their preparation and their use in the treatment of neurodegenerative or neurological disorders of the central nervous system | |
| TW200800976A (en) | New compounds for the treatment of neurological, psychiatric or pain disorders | |
| AU2002327378A1 (en) | Treatment of neuropsychiatric disorders by near-diaphragmatic nerve stimulation | |
| YU45204A (sh) | 3-BETA-D-RIBOFURANOZILTIAZOLO/4,5-d/ PIRIMIDINSKI NUKLEOZIDII NJIHOVA UPOTREBA | |
| GB0111186D0 (en) | Novel compounds | |
| ATE508114T1 (de) | Mit n-alkylhydroxamsäuren substituierte isoindolylverbindungen und deren pharmazeutische verwendung | |
| ATE223399T1 (de) | Quinazolin-4-on ampa antagonisten | |
| MY124786A (en) | Bis-arylsulfones | |
| MY120976A (en) | 2-amino-6-(2-substituted-4-phenoxy)- substituted- pyridines | |
| AU2001266152A1 (en) | Novel substituted nitrocatechols, their use in the treatment of some central andperipheral nervous system disorders and pharmaceutical compositions containing them | |
| TW200621716A (en) | Novel compounds | |
| TW200514781A (en) | Novel compounds | |
| BR0013781A (pt) | Pirazolo [4,3-d]pirimidinas | |
| ATE439363T1 (de) | Imidazo 2,1-b -1,3,4-thiadiazole sulfonamides | |
| TW200612969A (en) | 3-β-d-ribofuranosylthiazolo[4,5-d]pyrimidine nucleosides and uses thereof | |
| TW200611701A (en) | Novel compounds | |
| UY26426A1 (es) | Nuevos compuestos | |
| BG103687A (en) | Atropisomers of 3-heteroaryl-4(3h)-quinazolinones for the treatment of neurodegenerative processes and conditions related to the central nervous system | |
| MX2007006754A (es) | Derivados de indenilo y uso de los mismos para el tratamiento de trastornos neurologicos. | |
| DK1185293T3 (da) | IL6RIL6-kimær til behandling af neurodegenerative sygdomme | |
| AU4910500A (en) | Inhibitors of proton-gated cation channels and their use in the treatment of ischaemic disorders |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| RER | Ceased as to paragraph 5 lit. 3 law introducing patent treaties |