CA2680104C - 3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives - Google Patents
3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives Download PDFInfo
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- CA2680104C CA2680104C CA2680104A CA2680104A CA2680104C CA 2680104 C CA2680104 C CA 2680104C CA 2680104 A CA2680104 A CA 2680104A CA 2680104 A CA2680104 A CA 2680104A CA 2680104 C CA2680104 C CA 2680104C
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- 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
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP07103654 | 2007-03-07 | ||
| EP07103654.5 | 2007-03-07 | ||
| PCT/EP2007/052442 WO2007104783A2 (en) | 2006-03-15 | 2007-03-15 | 1,4 -di substituted 3-cyano-pyridone derivatives and their use as positive mglur2-recept0r modulators |
| EPPCT/EP2007/052442 | 2007-03-15 | ||
| EP07116403.2 | 2007-09-14 | ||
| EP07116403 | 2007-09-14 | ||
| PCT/EP2008/052768 WO2008107481A1 (en) | 2007-03-07 | 2008-03-07 | 3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2680104A1 CA2680104A1 (en) | 2008-09-12 |
| CA2680104C true CA2680104C (en) | 2016-05-31 |
Family
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| Application Number | Title | Priority Date | Filing Date |
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| CA2680104A Expired - Fee Related CA2680104C (en) | 2007-03-07 | 2008-03-07 | 3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives |
Country Status (18)
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| EP (1) | EP2134708B1 (enExample) |
| JP (1) | JP5357061B2 (enExample) |
| KR (1) | KR20090125814A (enExample) |
| CN (1) | CN101711244B (enExample) |
| AR (1) | AR065654A1 (enExample) |
| AT (1) | ATE509020T1 (enExample) |
| AU (1) | AU2008223796B2 (enExample) |
| BR (1) | BRPI0808509A2 (enExample) |
| CA (1) | CA2680104C (enExample) |
| DK (1) | DK2134708T3 (enExample) |
| EA (1) | EA017294B1 (enExample) |
| IL (1) | IL200329A0 (enExample) |
| MX (1) | MX2009009424A (enExample) |
| NZ (1) | NZ579988A (enExample) |
| PL (1) | PL2134708T3 (enExample) |
| TW (1) | TW200845978A (enExample) |
| WO (1) | WO2008107481A1 (enExample) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0420722D0 (en) * | 2004-09-17 | 2004-10-20 | Addex Pharmaceuticals Sa | Novel allosteric modulators |
| AR059898A1 (es) | 2006-03-15 | 2008-05-07 | Janssen Pharmaceutica Nv | Derivados de 3-ciano-piridona 1,4-disustituida y su uso como moduladores alostericos de los receptores mglur2 |
| AR065622A1 (es) * | 2007-03-07 | 2009-06-17 | Ortho Mcneil Janssen Pharm | Derivados de 3-ciano -4- (4-fenil- piperidin -1- il) piridin -2- ona |
| TW200845978A (en) | 2007-03-07 | 2008-12-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives |
| TW200900065A (en) | 2007-03-07 | 2009-01-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-pyridinyloxy-phenyl)-pyridin-2-one derivatives |
| JP5550352B2 (ja) | 2007-03-15 | 2014-07-16 | ノバルティス アーゲー | 有機化合物およびその使用 |
| ES2409215T3 (es) * | 2007-09-14 | 2013-06-25 | Janssen Pharmaceuticals, Inc. | 4-fenil-1H-piridin-2-onas 1-3-disustituidas |
| BRPI0817101A2 (pt) | 2007-09-14 | 2017-05-09 | Addex Pharmaceuticals Sa | 4-(aril-x-fenil)-1h-piridin-2-onas 1,3-dissubstituídas |
| SI2203439T1 (sl) | 2007-09-14 | 2011-05-31 | Ortho Mcneil Janssen Pharm | 1',3'-disubstituirani 4-fenil-3,4,5,6-tetrahidro-2H-1'H-(1,4')bipiridinil-2'-oni |
| ES2637794T3 (es) | 2007-11-14 | 2017-10-17 | Janssen Pharmaceuticals, Inc. | Derivados de imidazo[1,2-A]piridina y su uso como moduladores alostéricos positivos de receptores MGLUR2 |
| US20100041663A1 (en) | 2008-07-18 | 2010-02-18 | Novartis Ag | Organic Compounds as Smo Inhibitors |
| ES2439291T3 (es) | 2008-09-02 | 2014-01-22 | Janssen Pharmaceuticals, Inc. | Derivados de 3-azabiciclo[3.1.0]hexilo como moduladores de receptores de glutamato metabotrópicos |
| WO2010038167A1 (en) * | 2008-10-02 | 2010-04-08 | Pfizer Inc. | Oxopiperidinyl and pyranyl sulfonamides as ampa potentiators |
| CA2738849C (en) | 2008-10-16 | 2016-06-28 | Addex Pharma S.A. | Indole and benzomorpholine derivatives as modulators of metabotropic glutamate receptors |
| ES2401691T3 (es) | 2008-11-28 | 2013-04-23 | Ortho-Mcneil-Janssen Pharmaceuticals, Inc. | Derivados de indol y de benzoxacina como moduladores de los receptores metabotrópicos de glutamato |
| SG176018A1 (en) | 2009-05-12 | 2011-12-29 | Janssen Pharmaceuticals Inc | 1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
| ES2440001T3 (es) | 2009-05-12 | 2014-01-27 | Janssen Pharmaceuticals, Inc. | Derivados de 1,2,4-triazolo[4,3-A]piridina y su uso para el tratamiento o prevención de trastornos neurológicos y psiquiátricos |
| MY153913A (en) | 2009-05-12 | 2015-04-15 | Janssen Pharmaceuticals Inc | 7-aryl-1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
| CA2814998C (en) | 2010-11-08 | 2019-10-29 | Janssen Pharmaceuticals, Inc. | 1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
| ES2552455T3 (es) | 2010-11-08 | 2015-11-30 | Janssen Pharmaceuticals, Inc. | Derivados de 1,2,4-triazolo[4,3-a]piridina y su uso como moduladores alostéricos positivos de receptores mGluR2 |
| CN103298809B (zh) | 2010-11-08 | 2016-08-31 | 杨森制药公司 | 1,2,4-三唑并[4,3-a]吡啶衍生物及其作为MGLUR2受体的正变构调节剂的用途 |
| JO3368B1 (ar) | 2013-06-04 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 6، 7- ثاني هيدرو بيرازولو [5،1-a] بيرازين- 4 (5 يد)- اون واستخدامها بصفة منظمات تفارغية سلبية لمستقبلات ميجلور 2 |
| JP6026024B2 (ja) | 2013-06-27 | 2016-11-16 | ファイザー・インク | 複素芳香族化合物およびそのドーパミンｄ１リガンドとしての使用 |
| JO3367B1 (ar) | 2013-09-06 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 2،1، 4- ثلاثي زولو [3،4-a] بيريدين واستخدامها بصفة منظمات تفارغية موجبة لمستقبلات ميجلور 2 |
| US10537573B2 (en) | 2014-01-21 | 2020-01-21 | Janssen Pharmaceutica Nv | Combinations comprising positive allosteric modulators or orthosteric agonists of metabotropic glutamatergic receptor subtype 2 and their use |
| IL279202B2 (en) | 2014-01-21 | 2023-09-01 | Janssen Pharmaceutica Nv | Combinations containing positive allosteric modulators or orthosteric agonists of metabotropic glutamatergic subtype 2 receptor and their use |
| CN105153027A (zh) * | 2015-07-21 | 2015-12-16 | 东华大学 | 一种3-氰基-4-羟基-2-吡啶酮类化合物及其制备和应用 |
| EP3870292A4 (en) | 2018-10-26 | 2022-11-09 | The Research Foundation for The State University of New York | COMBINATION OF SEROTONIN-SPECIFIC RESUPPUT INHIBITOR AND SEROTONIN 1A RECEPTOR PARTIAL AGONIST TO REDUCE L-DOPA-INDUCED DYSKINESIA |
| MX2023009059A (es) | 2021-02-02 | 2023-09-15 | Liminal Biosciences Ltd | Antagonistas de gpr84 y usos de estos. |
Family Cites Families (440)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE790440A (enExample) | 1971-10-23 | 1973-04-24 | Bayer Ag | |
| JPS50106981U (enExample) | 1974-02-08 | 1975-09-02 | ||
| US3906953A (en) | 1974-05-23 | 1975-09-23 | American Optical Corp | Endoscopic surgical laser system |
| SU509578A1 (ru) | 1974-09-19 | 1976-04-05 | Стерлитамакский Химический Завод | Способ получени пропилендиаминов |
| GB1502312A (en) | 1975-03-20 | 1978-03-01 | Ici Ltd | Quinolone derivatives |
| IE43079B1 (en) | 1975-03-20 | 1980-12-17 | Ici Ltd | Quinolone derivatives |
| FR2311776A1 (fr) | 1975-05-23 | 1976-12-17 | Sogeras | Diamino-2,4 bromo-5 chloro-6 pyrimidines et procede pour leur preparation |
| GB1570494A (en) | 1975-11-28 | 1980-07-02 | Ici Ltd | Thienopyrimidine derivatives and their use as pesticides |
| JPS5382783U (enExample) | 1976-12-13 | 1978-07-08 | ||
| JPS5752334Y2 (enExample) | 1977-03-16 | 1982-11-13 | ||
| ZA782648B (en) | 1977-05-23 | 1979-06-27 | Ici Australia Ltd | The prevention,control or eradication of infestations of ixodid ticks |
| DE2750288A1 (de) | 1977-11-10 | 1979-05-17 | Thomae Gmbh Dr K | Neue 9-(omega-heteroarylamino- alkylamino)-erythromycine, ihre salze, verfahren zu ihrer herstellung und diese enthaltende arzneimittel |
| US4432979A (en) | 1981-10-26 | 1984-02-21 | William H. Rorer, Inc. | Pyridone compounds |
| EP0082023A3 (en) | 1981-12-16 | 1983-07-20 | Sankyo Company Limited | Thienopyrimidine derivatives, their preparation and their medical use |
| US4358453A (en) | 1982-01-08 | 1982-11-09 | Schering Corporation | 1,2,4-Triazolo[4,3-a]pyridines |
| US4520025A (en) | 1982-07-21 | 1985-05-28 | William H. Rorer, Inc. | Bicyclic nitrogen heterocyclic ethers and thioethers, and their pharmaceutical uses |
| DE3406329A1 (de) | 1984-02-22 | 1985-08-22 | Merck Patent Gmbh, 6100 Darmstadt | Pyridone |
| US4550166A (en) | 1984-05-21 | 1985-10-29 | American Cyanamid Company | (Pyridinyl)-1,2,4-triazolo[4,3-a]pyridines |
| US5175157A (en) | 1985-11-27 | 1992-12-29 | Boehringer Ingelheim Gmbh | Cyclic amine derivatives, pharmaceutical compositions containing these compounds and methods for preparing them |
| DE3717561A1 (de) | 1987-05-25 | 1988-12-08 | Thomae Gmbh Dr K | Indol-, isochinolin- und benzazepinderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| US4866074A (en) | 1987-05-08 | 1989-09-12 | Rorer Pharmaceutical Corporation | Naphtheridinone- and pyridooxazinone-pyridone compounds, cardiotonic compositions including same, and their uses |
| EP0308020A3 (en) | 1987-09-18 | 1990-12-05 | Merck & Co. Inc. | 5-(aryl and heteroaryl)-6-(aryl and heteroaryl)-1,2-dihydro-2-oxo 3-pyridinecarboxylic acids and derivatives thereof |
| US5260293A (en) | 1988-01-30 | 1993-11-09 | Merck Sharp & Dohme Limited | Pyrazines, pyrimidines and pyridazines useful in the treatment of senile dementia |
| GB8804448D0 (en) | 1988-02-25 | 1988-03-23 | Smithkline Beckman Intercredit | Compounds |
| JP2614081B2 (ja) | 1988-05-27 | 1997-05-28 | 大塚化学株式会社 | 光学活性β−ラクタム誘導体の製造法 |
| ES2075071T3 (es) | 1988-10-20 | 1995-10-01 | Sandoz Ag | Colorantes azoicos reactivos con fibras. |
| US5032602A (en) | 1988-12-14 | 1991-07-16 | Bayer Aktiengesellschaft | Inhibiting HMG-CoA reductase with novel substituted 2-pyridones and pyrid-2-thiones |
| HU206337B (en) | 1988-12-29 | 1992-10-28 | Mitsui Petrochemical Ind | Process for producing pyrimidine derivatives and pharmaceutical compositions |
| US5236917A (en) | 1989-05-04 | 1993-08-17 | Sterling Winthrop Inc. | Saccharin derivatives useful as proteolytic enzyme inhibitors and compositions and method of use thereof |
| US5280026A (en) | 1989-05-30 | 1994-01-18 | Smithkline Beecham Intercredit B.V. | Thienopyrimidines |
| AU622330B2 (en) | 1989-06-23 | 1992-04-02 | Takeda Chemical Industries Ltd. | Condensed heterocyclic compounds having a nitrogen atom in the bridgehead for use as fungicides |
| US4978663A (en) | 1989-08-16 | 1990-12-18 | Hoechst-Roussel Pharmaceuticals Inc. | 5-(1-aminocyclohexyl)-2(1H)-pyridinone compounds which have pharmaceutical utility |
| GB8926560D0 (en) | 1989-11-24 | 1990-01-17 | Zambeletti Spa L | Pharmaceuticals |
| IL96432A0 (en) | 1989-11-30 | 1991-08-16 | Schering Ag | Pesticidal compositions containing pyridine derivatives and novel pyridine derivatives |
| DE3940480A1 (de) | 1989-12-07 | 1991-06-13 | Bayer Ag | Chromogene enaminverbindungen, ihre herstellung und verwendung als farbbildner |
| AU6979091A (en) | 1989-12-22 | 1991-07-24 | Upjohn Company, The | Pyridinones useful as antiatherosclerotic agents |
| FR2657610A1 (fr) | 1990-01-29 | 1991-08-02 | Rhone Poulenc Agrochimie | Triazolopyridines herbicides. |
| GB9104238D0 (en) | 1990-03-16 | 1991-04-17 | Ici Pharma | 3-tetrazolylthiomethyl cephalosporin antibiotics |
| DE4008726A1 (de) | 1990-03-19 | 1991-09-26 | Basf Ag | Thieno(2,3-d)pyrimidinderivate |
| BR9101256A (pt) | 1990-03-30 | 1991-11-05 | Dowelanco | Composto,composicao fungicida,processo fungicida,composicao inseticida ou acaricida e processo inseticida ou acaricida |
| RU1796625C (ru) | 1990-06-27 | 1993-02-23 | Киевский Государственный Университет Им.Т.Г.Шевченко | 3-Амино-7-нитро-4(2,3,4-триметоксифенил)-2-фенил-1(2Н)изохинолон, обладающий аналептическим действием |
| ATE180475T1 (de) | 1990-09-21 | 1999-06-15 | Rohm & Haas | Dihydropyridazinone und pyridazinone als fungizide |
| WO1992018115A1 (en) | 1991-04-18 | 1992-10-29 | Dr Lo Zambeletti S.P.A. | Use of heterocyclic compounds for the treatment of inflammatory pain |
| DE4122240A1 (de) | 1991-07-05 | 1993-01-07 | Boehringer Mannheim Gmbh | Dibenz(b,e)azepinderivate und diese enthaltende arzneimittel |
| DE4129340A1 (de) | 1991-09-04 | 1993-03-11 | Merck Patent Gmbh | 1,2-dihydro-2-oxopyridine |
| US5332750A (en) | 1991-09-04 | 1994-07-26 | Merck Patent Gesellschaft Mit Beschrankter Haftung | 1,2-dihydro-2-oxopyridines |
| DE4131924A1 (de) | 1991-09-25 | 1993-07-08 | Hoechst Ag | Substituierte 4-alkoxypyrimidine, verfahren zu ihrer herstellung und ihre verwendung als schaedlingsbekaempfungsmittel |
| US5204198A (en) | 1991-10-28 | 1993-04-20 | Eastman Kodak Company | Photoelectrographic elements utilizing nonionic sulfonic acid photogenerators |
| US5416099A (en) | 1991-10-29 | 1995-05-16 | Merck & Co., Inc. | Fibrinogen receptor antagonists |
| DE4221583A1 (de) | 1991-11-12 | 1993-05-13 | Bayer Ag | Substituierte biphenylpyridone |
| JP2878531B2 (ja) | 1991-12-16 | 1999-04-05 | 富士写真フイルム株式会社 | ハロゲン化銀写真感光材料 |
| US5378720A (en) | 1991-12-19 | 1995-01-03 | Sterling Winthrop Inc. | Saccharin derivative proteolytic enzyme inhibitors |
| AU668694B2 (en) | 1991-12-19 | 1996-05-16 | Sanofi-Synthelabo | Saccharin derivative proteolytic enzyme inhibitors |
| TW219935B (enExample) | 1991-12-25 | 1994-02-01 | Mitsubishi Chemicals Co Ltd | |
| GB9200293D0 (en) | 1992-01-08 | 1992-02-26 | Wyeth John & Brother Ltd | Piperazine derivatives |
| GB9201694D0 (en) | 1992-01-27 | 1992-03-11 | Smithkline Beecham Intercredit | Compounds |
| JP3042156B2 (ja) | 1992-02-20 | 2000-05-15 | 田辺製薬株式会社 | ナフタレン誘導体、その製法及びその合成中間体 |
| DE4206045A1 (de) | 1992-02-27 | 1993-09-02 | Bayer Ag | Sulfonylbenzyl substituierte pyridone |
| US5922773A (en) | 1992-12-04 | 1999-07-13 | The Children's Medical Center Corp. | Glaucoma treatment |
| AU660132B2 (en) | 1992-12-21 | 1995-06-08 | Bayer Aktiengesellschaft | Substituted 4-phenyl-pyridones and 4-phenyl-2-alkoxypyridine |
| SE9300657D0 (sv) | 1993-02-26 | 1993-02-26 | Astra Ab | New compounds |
| US5814645A (en) | 1993-03-24 | 1998-09-29 | Bayer Aktiengesellschaft | Arylor hetaryl substituted nitrogen heterocycles and their use as pesticides |
| DE4316077A1 (de) | 1993-05-13 | 1994-11-17 | Bayer Ag | Substituierte Mono- und Bihydridylmethylpyridone |
| AU7102394A (en) | 1993-06-09 | 1995-01-03 | Smithkline Beecham Corporation | Bicyclic fibrinogen antagonists |
| DE4326758A1 (de) | 1993-08-10 | 1995-02-16 | Basf Ag | [1,3,4]Triazolo[1,5-a]pyridine |
| AU682396B2 (en) | 1993-08-19 | 1997-10-02 | Janssen Pharmaceutica N.V. | Vasoconstrictive substituted aryloxyalkyl diamines |
| RU2129556C1 (ru) | 1993-08-19 | 1999-04-27 | Жансен Фармасетика Н.В. | Производное дигидробензопирана, обладающее сосудосуживающим действием, промежуточные соединения, способы получения, фармацевтическая композиция и способ ее получения |
| AU7467294A (en) | 1993-08-20 | 1995-03-21 | Banyu Pharmaceutical Co., Ltd. | Tyrosine kinase inhibitor |
| US5424435A (en) | 1993-10-18 | 1995-06-13 | Olin Corporation | 1-hydroxy-6-substituted-2-pyridones |
| US5500420A (en) | 1993-12-20 | 1996-03-19 | Cornell Research Foundation, Inc. | Metabotropic glutamate receptor agonists in the treatment of cerebral ischemia |
| US5654307A (en) | 1994-01-25 | 1997-08-05 | Warner-Lambert Company | Bicyclic compounds capable of inhibiting tyrosine kinases of the epidermal growth factor receptor family |
| TW282456B (enExample) | 1994-03-10 | 1996-08-01 | Fujisawa Yakusin Kogyo Kk | |
| ES2079323B1 (es) | 1994-06-21 | 1996-10-16 | Vita Invest Sa | Derivados de indol utiles para el tratamiento de la migraña, composicion y uso correspondientes. |
| GB9416554D0 (en) | 1994-08-19 | 1994-10-12 | Ciba Geigy Ag | Glutamate receptor |
| JPH10504569A (ja) | 1994-08-24 | 1998-05-06 | イーライ・リリー・アンド・カンパニー | 向代謝性グルタメート受容体拮抗剤としてのピロリジニルジカルボン酸誘導体 |
| US5473077A (en) | 1994-11-14 | 1995-12-05 | Eli Lilly And Company | Pyrrolidinyl di-carboxylic acid derivatives as metabotropic glutamate receptor agonists |
| US6017697A (en) | 1994-11-14 | 2000-01-25 | Eli Lilly And Company | Excitatory amino acid receptor protein and related nucleic acid compounds |
| US5512576A (en) | 1994-12-02 | 1996-04-30 | Sterling Winthrop Inc. | 2-substituted 1,2,5,-thiadiazolidin-3-one 1,1-dioxides and compositions and method of use thereof |
| US5789426A (en) | 1995-01-20 | 1998-08-04 | Cornell Research Foundation, Inc. | Method for the treatment of fibroproliferative disorders by application of inhibitors of protein hydroxylation |
| US5869486A (en) | 1995-02-24 | 1999-02-09 | Ono Pharmaceutical Co., Ltd. | Fused pyrimidines and pyriazines as pharmaceutical compounds |
| DE19507522C2 (de) | 1995-03-03 | 2003-05-28 | Basf Ag | Verfahren zur Herstellung von 3,4-Dihydroisochinolinverbindungen und 3,4-Dihydroisochinolinium-Salzen |
| TW324008B (en) | 1995-03-13 | 1998-01-01 | Ishihara Sangyo Kaisha | Pyridone sulfonylurea compound, its production process and weed killer containing such compound |
| DE19510965A1 (de) | 1995-03-24 | 1996-09-26 | Asta Medica Ag | Neue Pyrido/3,2-e/pyrazinone mit antiasthmatischer Wirksamkeit und Verfahren zu deren Herstellung |
| CA2219364A1 (en) | 1995-04-27 | 1996-10-31 | Hideki Okunishi | Heterocyclic amide compounds and pharmaceutical use thereof |
| JPH08325248A (ja) | 1995-05-26 | 1996-12-10 | Chugoku Kayaku Kk | テトラゾール類の新規な合成試薬及びそれを用いたテトラゾール類の製造方法 |
| US5849587A (en) | 1995-06-09 | 1998-12-15 | Cornell Research Foundation, Inc. | Method of inhibiting viral replication in eukaryotic cells and of inducing apoptosis of virally-infected cells |
| US5659033A (en) | 1995-09-13 | 1997-08-19 | Neurogen Corporation | N-aminoalkylfluorenecarboxamides; a new class of dopamine receptor subtype specific ligands |
| BR9610579A (pt) | 1995-09-15 | 1999-07-06 | Sanofi Synthelabo | Derivados de quinolein-2(1H)-ona como antagonistas da serotonina |
| US6130217A (en) | 1995-09-20 | 2000-10-10 | Pfizer Inc | Compounds enhancing antitumor activity of other cytotoxic agents |
| JPH1045750A (ja) | 1995-09-20 | 1998-02-17 | Takeda Chem Ind Ltd | アゾール化合物、その製造方法及び用途 |
| AR004010A1 (es) | 1995-10-11 | 1998-09-30 | Glaxo Group Ltd | Compuestos heterociclicos |
| SK283335B6 (sk) | 1995-12-08 | 2003-06-03 | Janssen Pharmaceutica N. V. | (Imidazol-5-yl)metyl-2-chinolinónové deriváty, spôsob a medziprodukty na ich prípravu, ich použitie a farmaceutické kompozície na ich báze |
| AU1608397A (en) | 1996-02-02 | 1997-08-22 | Zeneca Limited | Heterocyclic compounds useful as pharmaceutical agents |
| GB9602166D0 (en) | 1996-02-02 | 1996-04-03 | Zeneca Ltd | Aminoheterocyclic derivatives |
| GB9602294D0 (en) | 1996-02-05 | 1996-04-03 | Zeneca Ltd | Heterocyclic compounds |
| US6084084A (en) | 1996-02-21 | 2000-07-04 | Nps Pharmaceuticals, Inc. | Human metabotropic glutamate receptor |
| US5710274A (en) | 1996-02-28 | 1998-01-20 | Neurogen Corporation | N-aminoalkyldibenzofurancarboxamides; new dopamine receptor subtype specific ligands |
| US5756518A (en) | 1996-04-02 | 1998-05-26 | Kowa Co., Ltd. | Phenylene derivatives |
| JPH1029979A (ja) | 1996-04-12 | 1998-02-03 | Ajinomoto Co Inc | 新規ピリジン誘導体 |
| WO1997046532A1 (en) | 1996-06-03 | 1997-12-11 | Boehringer Ingelheim Pharmaceuticals, Inc. | 2-benzyl-4-sulfonyl-4h-isoquinolin-1,3-diones and their use as anti-inflammatory agents |
| WO1998006724A1 (en) | 1996-08-09 | 1998-02-19 | Yamanouchi Pharmaceutical Co., Ltd. | Metabotropic glutamate receptor agonists |
| DE19632423A1 (de) | 1996-08-12 | 1998-02-19 | Merck Patent Gmbh | Thienopyrimidine |
| PL331599A1 (en) | 1996-08-14 | 1999-08-02 | Zeneca Ltd | Substituted derivatives of pyrimidine and their pharmaceutical application |
| ATE213495T1 (de) | 1996-09-16 | 2002-03-15 | Du Pont Pharm Co | Eine resorbierbare röntgenopake markierung enthaltendes chirurgisches implantat und verfahren zum verriegeln desselben in einem körper |
| DE19638486A1 (de) | 1996-09-20 | 1998-03-26 | Basf Ag | Hetaroylderivate |
| DE19638484A1 (de) | 1996-09-20 | 1998-03-26 | Basf Ag | Hetaroylderivate |
| DE19644228A1 (de) | 1996-10-24 | 1998-04-30 | Merck Patent Gmbh | Thienopyrimidine |
| US6284794B1 (en) | 1996-11-05 | 2001-09-04 | Head Explorer Aps | Method for treating tension-type headache with inhibitors of nitric oxide and nitric oxide synthase |
| BR9713863A (pt) | 1996-12-05 | 2000-03-14 | Amgen Inc | Composto ou um sal farmaceuticamente aceitável do mesmo, composição farmacêutica, processos de profilaxia ou tratamento, para abaixar as concentrações no plasma, para diminuir a produção de prostaglandinas, e, para diminuir a atividade de enzima ciclooxigenase |
| NZ336676A (en) | 1997-01-24 | 2000-01-28 | Norsk Hydro As | Gemcitabine esters or amides useful as anti-cancer and anti-viral agents |
| US5855654A (en) | 1997-01-30 | 1999-01-05 | Rohm And Haas Company | Pyridazinones as marine antifouling agents |
| FR2759366B1 (fr) | 1997-02-11 | 1999-04-16 | Centre Nat Rech Scient | Composes constituant notamment des effecteurs de recepteurs du systeme nerveux central sensibles aux amino acides neuroexcitateurs, leur preparation et leurs applications biologiques |
| US6262068B1 (en) | 1997-02-21 | 2001-07-17 | Bristol-Myers Squibb Company | Lactam derivatives as antiarrhythmic agents |
| AU6230098A (en) | 1997-02-27 | 1998-09-18 | Tanabe Seiyaku Co., Ltd. | Isoquinolinone derivatives, process for preparing the same, and their use as phosphodiesterase inhibitors |
| ES2131463B1 (es) | 1997-04-08 | 2000-03-01 | Lilly Sa | Derivados de ciclopropilglicina con propiedades farmaceuticas. |
| GB9708945D0 (en) | 1997-05-01 | 1997-06-25 | Merck Sharp & Dohme | Therapeutic agents |
| DE19728996A1 (de) | 1997-07-07 | 1999-01-14 | Basf Ag | Triazolverbindungen und deren Verwendung |
| SI0891978T1 (en) | 1997-07-18 | 2002-06-30 | F. Hoffmann-La Roche Ag | 5H-Thiazolo (3,2-a) pyrimidine derivatives |
| JP2001515839A (ja) | 1997-07-18 | 2001-09-25 | ジョージタウン・ユニバーシティ | 二環式向代謝性グルタミン酸受容体リガンド |
| US6214857B1 (en) | 1997-07-31 | 2001-04-10 | Celgene Corporation | Substituted alkanohydroxamic acids and method of reducing TNFα levels |
| HRP20000079A2 (en) | 1997-08-14 | 2000-12-31 | Hoffmann La Roche | Heterocyclic vinylethers against neurological disorders |
| US6358975B1 (en) | 1997-08-15 | 2002-03-19 | Johns Hopkins University | Method of using selective parp inhibitors to prevent or treat neurotoxicity |
| US6121278A (en) | 1997-09-03 | 2000-09-19 | Guilford Pharmaceuticals, Inc. | Di-n-heterocyclic compounds, methods, and compositions for inhibiting parp activity |
| US20020028813A1 (en) | 1997-09-03 | 2002-03-07 | Paul F. Jackson | Thioalkyl compounds, methods, and compositions for inhibiting parp activity |
| WO1999011622A1 (en) | 1997-09-03 | 1999-03-11 | Guilford Pharmaceuticals Inc. | Amino-substituted compounds, methods, and compositions for inhibiting parp activity |
| US20020022636A1 (en) | 1997-09-03 | 2002-02-21 | Jia-He Li | Oxo-substituted compounds, process of making, and compositions and methods for inhibiting parp activity |
| US6635642B1 (en) | 1997-09-03 | 2003-10-21 | Guilford Pharmaceuticals Inc. | PARP inhibitors, pharmaceutical compositions comprising same, and methods of using same |
| US6197785B1 (en) | 1997-09-03 | 2001-03-06 | Guilford Pharmaceuticals Inc. | Alkoxy-substituted compounds, methods, and compositions for inhibiting PARP activity |
| WO1999012532A2 (en) | 1997-09-08 | 1999-03-18 | F.Hoffmann-La Roche Ag | Piperidine derivatives against malaria |
| DE69815008T2 (de) | 1997-09-19 | 2004-04-01 | Ssp Co., Ltd. | Alfa-substituierte Phenylpropionsäurederivate und diese enthaltende Arzneimittel |
| US6465484B1 (en) | 1997-09-26 | 2002-10-15 | Merck & Co., Inc. | Angiogenesis inhibitors |
| CA2303830A1 (en) | 1997-09-26 | 1999-04-08 | Merck & Co., Inc. | Novel angiogenesis inhibitors |
| US6162804A (en) | 1997-09-26 | 2000-12-19 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| JP2001519345A (ja) | 1997-10-02 | 2001-10-23 | メルク エンド カムパニー インコーポレーテッド | プレニルタンパク質トランスフェラーゼの阻害剤 |
| BR9814820A (pt) | 1997-10-14 | 2000-10-03 | Welfide Corp | Compostos de piperazina e seu uso médico |
| WO1999021992A2 (en) | 1997-10-23 | 1999-05-06 | Ganimed Pharmaceuticals Gmbh | Nucleic acid molecules encoding a glutamate receptor |
| JP4321737B2 (ja) | 1997-12-17 | 2009-08-26 | 塩野義製薬株式会社 | 新規ピリジン化合物 |
| US6013672A (en) | 1997-12-18 | 2000-01-11 | Uab Research Foundation | Agonists of metabotropic glutamate receptors and uses thereof |
| EP1045836B1 (en) | 1997-12-18 | 2008-03-05 | Boehringer Ingelheim Pharmaceuticals Inc. | Pyridones as src family sh2 domain inhibitors |
| EP1042293B9 (en) | 1997-12-19 | 2008-09-03 | Amgen Inc. | Substituted pyridine and pyridazine compounds and their pharmaceutical use |
| FR2772763B1 (fr) | 1997-12-24 | 2004-01-23 | Sod Conseils Rech Applic | Nouveaux analogues tetracycliques de camptothecines, leurs procedes de preparation, leur application comme medicaments et les compositions pharmaceutiques les contenant |
| IT1298155B1 (it) | 1998-01-19 | 1999-12-20 | Moreno Paolini | Composti pirimidin 3-ossido per il trattamento delle patologie muscolo-scheletriche, in particolare per il trattamento della |
| US6664250B2 (en) | 1998-01-20 | 2003-12-16 | Bristol-Myers Squibb Co. | Lactam derivatives as antiarrhythmic agents |
| EP1052246B1 (en) | 1998-01-28 | 2003-04-02 | Taisho Pharmaceutical Co., Ltd | Fluorine-containing amino acid derivatives |
| BR9908004A (pt) | 1998-02-17 | 2001-12-18 | Tularik Inc | Composto, composição e método para prevençãoou supressão de uma infecção viral |
| CZ20003355A3 (cs) | 1998-03-17 | 2002-05-15 | Pfizer Products Inc. | Bicyklo[2,2,1]heptany a příbuzné sloučeniny, farmaceutické kompozice a způsoby léčení na jejich bázi |
| JP2002511461A (ja) | 1998-04-08 | 2002-04-16 | ノバルティス アクチエンゲゼルシャフト | Ｎ−ピリドニル除草剤 |
| AU3170099A (en) | 1998-04-16 | 1999-11-08 | Yamanouchi Pharmaceutical Co., Ltd. | Remedies for obesity |
| EP0955301A3 (en) | 1998-04-27 | 2001-04-18 | Pfizer Products Inc. | 7-aza-bicyclo[2.2.1]-heptane derivatives, their preparation and use according to their affinity for neuronal nicotinic acetylcholine receptors |
| DE19822198C2 (de) | 1998-05-16 | 2003-02-13 | Wella Ag | Oxonolfarbstoffe enthaltende Mittel und Verfahren zur Erzeugung von semipermanenten Färbungen auf Haaren |
| IL139811A0 (en) | 1998-06-04 | 2002-02-10 | Abbott Lab | Cell adhesion-inhibiting antinflammatory compounds |
| DE19826671A1 (de) | 1998-06-16 | 1999-12-23 | Hoechst Schering Agrevo Gmbh | 1,3-Oxazolin- und 1,3-Thiazolin-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Schädlingsbekämpfungsmittel |
| FR2781218B1 (fr) | 1998-07-15 | 2001-09-07 | Lafon Labor | Compositions pharmaceutiques comprenant des 2-quinolones |
| JP2000072751A (ja) | 1998-08-26 | 2000-03-07 | Tanabe Seiyaku Co Ltd | イソキノリノン誘導体 |
| DE69918136T2 (de) | 1998-08-31 | 2005-07-07 | Taisho Pharmaceutical Co., Ltd. | 6-Fluorobicyclo[3.1.0]Hexan-Derivate |
| JP2000072731A (ja) | 1998-08-31 | 2000-03-07 | Taisho Pharmaceut Co Ltd | ４−置換−２−アミノビシクロ［３．１．０］ヘキサン−２，６−ジカルボン酸誘導体及び製薬用組成物 |
| CA2341409A1 (en) | 1998-08-31 | 2000-03-09 | Merck And Co., Inc. | Novel angiogenesis inhibitors |
| CH694053A5 (de) | 1998-09-03 | 2004-06-30 | Hoffmann La Roche | Verfahren zur Herstellung von 2-Amino-bicyclo[3.1.0]hexan-2,6-dicarbonsäure-Derivaten. |
| US6284759B1 (en) | 1998-09-30 | 2001-09-04 | Neurogen Corporation | 2-piperazinoalkylaminobenzo-azole derivatives: dopamine receptor subtype specific ligands |
| SE9803518D0 (sv) | 1998-10-15 | 1998-10-15 | Astra Pharma Prod | Novel compounds |
| PE20001236A1 (es) | 1998-11-13 | 2000-11-10 | Lilly Co Eli | Moduladores del receptor de aminoacidos excitadores |
| US6133271A (en) | 1998-11-19 | 2000-10-17 | Cell Pathways, Inc. | Method for inhibiting neoplastic cells and related conditions by exposure thienopyrimidine derivatives |
| US5948911A (en) | 1998-11-20 | 1999-09-07 | Cell Pathways, Inc. | Method for inhibiting neoplastic cells and related conditions by exposure to thienopyrimidine derivatives |
| EP1006112A1 (en) | 1998-12-01 | 2000-06-07 | Cerebrus Pharmaceuticals Limited | 3-Hydroxy-2(1H)-pyridinone or 3-hydroxy-4(1H)-pyridinone derivatives useful as reactive oxygen species (ROS) scavengers |
| JP2002531549A (ja) | 1998-12-04 | 2002-09-24 | ブリストル−マイヤーズ スクイブ カンパニー | カリウムチャネル・モジュレーターとしての３−置換−４−アリールキノリン−２−オン誘導体 |
| WO2000044277A2 (en) | 1999-02-01 | 2000-08-03 | A.C.Cossor & Son (Surgical) Limited | Improvements in or relating to sphygmomanometers and other devices |
| US6245759B1 (en) | 1999-03-11 | 2001-06-12 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| TW564247B (en) | 1999-04-08 | 2003-12-01 | Akzo Nobel Nv | Bicyclic heteraromatic compound |
| GB9908175D0 (en) | 1999-04-09 | 1999-06-02 | Lilly Co Eli | Method of treating neurological disorders |
| US6972296B2 (en) | 1999-05-07 | 2005-12-06 | Encysive Pharmaceuticals Inc. | Carboxylic acid derivatives that inhibit the binding of integrins to their receptors |
| US6723711B2 (en) | 1999-05-07 | 2004-04-20 | Texas Biotechnology Corporation | Propanoic acid derivatives that inhibit the binding of integrins to their receptors |
| EP1183238A1 (en) | 1999-05-17 | 2002-03-06 | Eli Lilly And Company | Metabotropic glutamate receptor antagonists |
| HK1048635A1 (zh) | 1999-06-02 | 2003-04-11 | Nps药物有限公司 | 代谢移变的谷氨酸盐受体拮抗剂和它们治疗中枢神经系统疾病的用途 |
| BR9916746A (pt) | 1999-06-03 | 2005-01-11 | Abbott Lab | Compostos anti-inflamatórios que inibem adesão de célula |
| EP1189873A1 (en) | 1999-06-03 | 2002-03-27 | Lilly, S.A. | Excitatory amino acid receptor modulators |
| JP4783967B2 (ja) | 1999-07-21 | 2011-09-28 | 大正製薬株式会社 | 含フッ素アミノ酸誘導体を有効成分とする医薬 |
| WO2001010846A2 (en) | 1999-08-05 | 2001-02-15 | Igt Pharma Inc. | 1,4-diazepine derivatives for the treatment of diseases related to the central nervous system |
| DE60006618T2 (de) * | 1999-08-06 | 2004-09-23 | F. Hoffmann-La Roche Ag | Tetrahydro-benzo(d)azepine und deren Verwendung als metabotrope Glutamatrezeptor-Antagonisten |
| US6660753B2 (en) | 1999-08-19 | 2003-12-09 | Nps Pharmaceuticals, Inc. | Heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists |
| US7040838B2 (en) | 1999-08-27 | 2006-05-09 | Kristar Enterprises, Inc. | High capacity catch basin filtration system with adjustable deflector ring |
| ATE261945T1 (de) | 1999-10-15 | 2004-04-15 | Hoffmann La Roche | Benzodiazepinderivate und deren verwendung als metabotrope glutamatrezeptor antagonisten |
| ATE250039T1 (de) | 1999-10-15 | 2003-10-15 | Hoffmann La Roche | Benzodiazepinderivate und deren verwendung als metabotrope glutamatrezeptor antagonisten |
| DZ3223A1 (fr) | 1999-10-19 | 2001-04-26 | Merck & Co Inc | Inhibiteurs de tyrosine kinases |
| SV2002000205A (es) | 1999-11-01 | 2002-06-07 | Lilly Co Eli | Compuestos farmaceuticos ref. x-01095 |
| GB2355982A (en) | 1999-11-03 | 2001-05-09 | Lilly Co Eli | Heterocyclic amino acids |
| WO2001046190A1 (en) | 1999-12-22 | 2001-06-28 | Kyorin Pharmaceutical Co., Ltd. | Tricyclic compounds and addition salts thereof |
| WO2001053288A1 (en) | 2000-01-20 | 2001-07-26 | Eisai Co., Ltd. | Novel piperidine compounds and drugs containing the same |
| GB0002100D0 (en) | 2000-01-28 | 2000-03-22 | Novartis Ag | Organic compounds |
| US6800651B2 (en) | 2000-02-03 | 2004-10-05 | Eli Lilly And Company | Potentiators of glutamate receptors |
| KR100521735B1 (ko) | 2000-02-25 | 2005-10-17 | 에프. 호프만-라 로슈 아게 | 아데노신 수용체 조절인자 |
| DE10012373A1 (de) | 2000-03-14 | 2001-09-20 | Dresden Arzneimittel | Verwendung von Pyrido[3,2-e]-pyrazinonen als Inhibitoren der Phosphodiesterase 5 zur Therapie von erektiler Dysfunktion |
| GB0007108D0 (en) | 2000-03-23 | 2000-05-17 | Novartis Ag | Organic compounds |
| US6469026B2 (en) | 2000-03-24 | 2002-10-22 | Millennium Pharmaceuticals, Inc. | Isoquinolone inhibitors of factor Xa |
| GB0007193D0 (en) | 2000-03-25 | 2000-05-17 | Univ Manchester | Treatment of movrmrnt disorders |
| US6403588B1 (en) | 2000-04-27 | 2002-06-11 | Yamanouchi Pharmaceutical Co., Ltd. | Imidazopyridine derivatives |
| JP3729343B2 (ja) | 2000-04-27 | 2005-12-21 | アステラス製薬株式会社 | 縮合ヘテロアリール誘導体 |
| AU2001252638A1 (en) | 2000-04-28 | 2001-11-12 | Nihon Nohyaku Co. Ltd. | Process for the preparation of 2-halobenzoic acids |
| EP1288199A4 (en) | 2000-04-28 | 2005-10-12 | Shionogi & Co | INHIBITORS OF MMP-12 |
| DE60103050T2 (de) | 2000-05-11 | 2005-01-20 | Kenneth Vancouver Curry | Spiro[2.4]heptanaminocarbonsäure und ihre derivate |
| WO2001085716A1 (en) | 2000-05-11 | 2001-11-15 | Kyowa Hakko Kogyo Co., Ltd | 2-piperidone compounds for the treatment of cancer |
| US20020009713A1 (en) | 2000-05-11 | 2002-01-24 | Miller Freda D. | Methods for identifying modulators of neuronal growth |
| US7081481B2 (en) | 2000-05-31 | 2006-07-25 | Eli Lilly And Company | Excitatory amino acid receptor modulators |
| MXPA02012314A (es) | 2000-06-12 | 2004-09-06 | Eisai Co Ltd | Compuestos de 1,2-dihidropiridina, metodo de fabricacion y utilizacion de los mismos. |
| JP2002003401A (ja) | 2000-06-27 | 2002-01-09 | Japan Science & Technology Corp | 脳由来神経栄養因子誘導剤 |
| WO2002000715A2 (en) | 2000-06-27 | 2002-01-03 | Centre National De La Recherche Scientifique-Cnrs | Mammal 2p domain mechano-sensitive k+ channel, cloning and applications thereof |
| JP2002012533A (ja) | 2000-06-27 | 2002-01-15 | Kao Corp | 染毛剤組成物 |
| CA2411059A1 (en) | 2000-06-28 | 2002-12-06 | Taisho Pharmaceutical Co., Ltd. | Novel dicarboxylic acid derivatives |
| DE10031390A1 (de) | 2000-07-03 | 2002-01-17 | Knoll Ag | Pyrimidinderivate und ihre Verwendung zur Prophylaxe und Therapie der zerebralen Ischämie |
| US20020041880A1 (en) | 2000-07-05 | 2002-04-11 | Defeo-Jones Deborah | Method of treating cancer |
| JP2002069057A (ja) | 2000-07-07 | 2002-03-08 | Kyowa Hakko Kogyo Co Ltd | ピペリジン誘導体 |
| JP2002040252A (ja) | 2000-07-27 | 2002-02-06 | Shiseido Co Ltd | コレステリック液晶層を含む光学シート、それを用いた情報記録体、情報記録方法並びに情報判別方法 |
| DE10038019A1 (de) | 2000-08-04 | 2002-02-14 | Bayer Ag | Substituierte Triazolopyrid(az)ine |
| EP1308441B1 (en) | 2000-08-11 | 2009-10-07 | Eisai R&D Management Co., Ltd. | 2-aminopyridine compounds and use thereof as drugs |
| PL211125B1 (pl) | 2000-09-11 | 2012-04-30 | Novartis Vaccines & Diagnostic | Pochodne chinolinonu jako inhibitory kinazy tyrozynowej, kompozycje je zawierające i ich zastosowanie |
| AU2002213422A1 (en) | 2000-09-13 | 2002-03-26 | Georgetown University | Synthesis of 2-hydroxymethylglutamic acid and congeners thereof |
| JP2002105085A (ja) | 2000-09-28 | 2002-04-10 | Yamanouchi Pharmaceut Co Ltd | 新規イミダゾチアゾール誘導体 |
| SK5212003A3 (en) | 2000-10-02 | 2004-03-02 | Janssen Pharmaceutica Nv | Metabotropic glutamate receptor antagonists |
| DE10058663A1 (de) | 2000-11-25 | 2002-05-29 | Merck Patent Gmbh | Verwendung von Thienopyrimidinen |
| WO2002051849A1 (en) | 2000-12-26 | 2002-07-04 | Daiichi Pharmaceutical Co., Ltd. | Cdk4 inhibitors |
| JP2002308882A (ja) | 2001-02-08 | 2002-10-23 | Yamanouchi Pharmaceut Co Ltd | チエノピリミジン誘導体 |
| AU2002258400A1 (en) | 2001-02-16 | 2002-08-28 | Tularik Inc. | Methods of using pyrimidine-based antiviral agents |
| CA2439263C (en) | 2001-03-02 | 2012-10-23 | Frank Becker | Three hybrid assay system |
| WO2002074025A2 (de) | 2001-03-08 | 2002-09-19 | Ilfa Industrieelektronik Und Leiterplattenfertigung Aller Art Gmbh | Mehrschichtige leiterplatte |
| US6596731B2 (en) | 2001-03-27 | 2003-07-22 | Hoffmann-La Roche Inc. | Substituted imidazo[1,2-A] pyridine derivatives |
| CA2443144A1 (en) | 2001-04-02 | 2002-10-10 | Merck & Co., Inc. | In vivo methods of determining activity of receptor-type kinase inhibitors |
| CA2442557C (en) | 2001-04-12 | 2008-12-23 | F. Hoffmann-La Roche Ag | Dihydro-benzo¬b|¬1,4|diazepin-2-one derivatives as mglur2 antagonists ii |
| NZ528345A (en) | 2001-04-12 | 2005-04-29 | F | Dihydro-benzo[b][1,4]diazepin-2-one derivatives as mGluR2 antagonists I |
| SE0101579D0 (sv) | 2001-05-04 | 2001-05-04 | Astrazeneca Ab | New compounds |
| CZ20033053A3 (en) | 2001-05-14 | 2004-05-12 | Bristol@Myersásquibbápharmaácompany | Substituted pyrazinones, pyridines and pyrimidines as corticotropin releasing factor ligands |
| US7144903B2 (en) | 2001-05-23 | 2006-12-05 | Amgen Inc. | CCR4 antagonists |
| CA2448317A1 (en) | 2001-05-30 | 2002-12-05 | Alteon Inc. | Method for treating glaucoma v |
| WO2002096363A2 (en) | 2001-05-30 | 2002-12-05 | Alteon, Inc. | Method for treating fibrotic diseases or other indications |
| DE60214392T2 (de) | 2001-06-05 | 2008-01-17 | Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield | 1,4-Disubstituierte Benzo-kondensierte Cycloalkyl-Harnstoffverbindungen |
| EP1408042A4 (en) | 2001-06-14 | 2005-02-02 | Banyu Pharma Co Ltd | NEW ISOXAZOLOPYRIDONE DERIVATIVES AND THEIR USE |
| HUP0402352A2 (hu) | 2001-06-19 | 2005-02-28 | Bristol-Myers Squibb Co. | Foszfodiészteráz (PDE) 7 inhibitorként alkalmazható pirimidinszármazékok és ezeket tartalmazó gyógyszerkészítmények |
| JP2003012653A (ja) | 2001-06-28 | 2003-01-15 | Yamanouchi Pharmaceut Co Ltd | キナゾリン誘導体 |
| EP1411941A2 (en) | 2001-08-02 | 2004-04-28 | Neurocrine Biosciences, Inc. | Pyridinone and pyridazinone derivatives as gonadotropin-releasing hormone receptor antagonists |
| EP1425284A2 (en) | 2001-09-11 | 2004-06-09 | Smithkline Beecham Corporation | Furo- and thienopyrimidine derivatives as angiogenesis inhibitors |
| WO2003029209A2 (en) | 2001-10-02 | 2003-04-10 | Smithkline Beecham Corporation | Chemical compounds |
| TWI330183B (enExample) | 2001-10-22 | 2010-09-11 | Eisai R&D Man Co Ltd | |
| TW200406466A (en) | 2001-11-13 | 2004-05-01 | Ciba Sc Holding Ag | Compositions comprising at least one oxonol dye and at least one metal complex |
| US6921762B2 (en) | 2001-11-16 | 2005-07-26 | Amgen Inc. | Substituted indolizine-like compounds and methods of use |
| GB0129260D0 (en) | 2001-12-06 | 2002-01-23 | Eisai London Res Lab Ltd | Pharmaceutical compositions and their uses |
| KR20040068240A (ko) | 2001-12-14 | 2004-07-30 | 노보 노르디스크 에이/에스 | 호르몬 민감성 리파아제의 활성을 감소시키기 위한 화합물및 그들의 사용 |
| US7998986B2 (en) | 2001-12-21 | 2011-08-16 | Exelixis Patent Company Llc | Modulators of LXR |
| NZ533699A (en) | 2001-12-27 | 2006-05-26 | Taisho Pharmaceutical Co Ltd | 6-fluorobicyclo[3.1.0]hexane derivatives |
| DE10164139A1 (de) | 2001-12-27 | 2003-07-10 | Bayer Ag | 2-Heteroarylcarbonsäureamide |
| JP2005170790A (ja) | 2002-01-09 | 2005-06-30 | Ajinomoto Co Inc | Ｎ−アルキルスルフォニル置換アミド誘導体 |
| JP2005515254A (ja) | 2002-01-17 | 2005-05-26 | スミスクライン ビーチャム コーポレーション | カテプシンｋ阻害剤として有用なシクロアルキルケトアミド誘導体 |
| US20050113283A1 (en) | 2002-01-18 | 2005-05-26 | David Solow-Cordero | Methods of treating conditions associated with an EDG-4 receptor |
| JP2005519915A (ja) | 2002-01-18 | 2005-07-07 | セレテック・リミテッド・ライアビリティ・カンパニー | Ｅｄｇ受容体に関連する症状の処置方法 |
| WO2003064428A1 (en) | 2002-01-29 | 2003-08-07 | H. Lundbeck A/S | Furano- and thienopyrimidines as neurokinase inhibitors |
| US6949542B2 (en) | 2002-02-06 | 2005-09-27 | Hoffman-La Roche Inc. | Dihydro-benzo[b][1,4]diazepin-2-one derivatives |
| AU2003210869A1 (en) | 2002-02-07 | 2003-09-02 | University Of Miami | Schwann cell and phosphodiesterase inhibitors based therapy |
| US20040116489A1 (en) | 2002-02-12 | 2004-06-17 | Massey Steven Marc | Synthetic excitatory amino acids |
| AU2003211931A1 (en) | 2002-02-13 | 2003-09-04 | Takeda Chemical Industries, Ltd. | Jnk inhibitor |
| ES2334990T3 (es) | 2002-02-14 | 2010-03-18 | Pharmacia Corporation | Piridinonas sustituidas como moduladores de p38 map quinasa. |
| AU2003205558A1 (en) | 2002-02-19 | 2003-09-09 | H. Lundbeck A/S | Thioibotenic acid and derivatives thereof |
| US6833380B2 (en) | 2002-03-07 | 2004-12-21 | Warner-Lambert Company, Llc | Compounds that modulate PPAR activity and methods of preparation |
| US20060046999A1 (en) | 2002-03-14 | 2006-03-02 | Cristina Alonso-Alija | Monocyclic aroylpyridinones as antiinflammatory agents |
| AU2003225964B2 (en) | 2002-03-28 | 2008-11-20 | Merck Sharp & Dohme Corp. | Substituted 2,3-diphenyl pyridines |
| MXPA04009435A (es) | 2002-03-29 | 2005-01-25 | Janssen Pharmaceutica Nv | Derivados de quinolina y quinolinona radiomarcados y su uso como ligandos de receptor de glutamato metabotropico. |
| CA2478227A1 (en) | 2002-04-03 | 2003-10-16 | Eli Lilly And Company | Therapy for psychoses combining an atypical antipsychotic and an mglu2/3 receptor agonist |
| US6864261B2 (en) | 2002-05-02 | 2005-03-08 | Euro-Celtique S.A. | Therapeutic agents useful for treating pain |
| DE60318198T2 (de) | 2002-05-02 | 2008-12-04 | Merck & Co., Inc. | Tyrosinkinase-hemmer |
| MXPA04011470A (es) | 2002-05-21 | 2005-02-14 | Amgen Inc | Compuestos heterociclicos sustituidos y metodos de uso. |
| DK1517915T3 (da) | 2002-06-11 | 2009-03-16 | Lilly Co Eli | Promedikamenter af excitatoriske aminosyrer |
| CA2489128C (en) | 2002-06-13 | 2012-01-03 | Vertex Pharmaceuticals Incorporated | 2-ureido-6-heteroaryl-3h-benzoimidazole-4-carboxylic acid derivatives and related compounds as gyrase and/or topoisomerase iv inhibitors for the treatment of bacterial infections |
| GB0214268D0 (en) | 2002-06-20 | 2002-07-31 | Celltech R&D Ltd | Chemical compounds |
| MY141867A (en) | 2002-06-20 | 2010-07-16 | Vertex Pharma | Substituted pyrimidines useful as protein kinase inhibitors |
| JP2005538975A (ja) | 2002-07-03 | 2005-12-22 | アステックス テクノロジー リミテッド | ｐ３８ＭＡＰキナーゼ阻害薬としての３−（ヘテロ）アリールメトキシピリジン類およびそれらの類縁体 |
| US7262194B2 (en) | 2002-07-26 | 2007-08-28 | Euro-Celtique S.A. | Therapeutic agents useful for treating pain |
| US20040138238A1 (en) | 2002-08-08 | 2004-07-15 | Dhanoa Dale S. | Substituted aminopyrimidine compounds as neurokinin antagonists |
| GB0218630D0 (en) | 2002-08-10 | 2002-09-18 | Tanabe Seiyaku Co | Novel compounds |
| GB0218800D0 (en) | 2002-08-13 | 2002-09-18 | Celltech R&D Ltd | Chemical compounds |
| WO2004017950A2 (en) | 2002-08-22 | 2004-03-04 | Piramed Limited | Phosphadidylinositol 3,5-biphosphate inhibitors as anti-viral agents |
| US20050288346A1 (en) * | 2002-08-26 | 2005-12-29 | Cube Rowena V | Acetophenone potentiators of metabotropic glutamate receptors |
| JP2006502152A (ja) | 2002-08-28 | 2006-01-19 | インターミューン インコーポレイテッド | 線維性疾患治療用の併用療法 |
| MY139563A (en) | 2002-09-04 | 2009-10-30 | Bristol Myers Squibb Co | Heterocyclic aromatic compounds useful as growth hormone secretagogues |
| US8354447B2 (en) | 2002-09-10 | 2013-01-15 | The Scripps Research Institute | mGLU receptors antagonists for treating disorders associated with mGLU receptors including addiction and depression |
| EP1546201A4 (en) | 2002-09-11 | 2006-08-16 | Merck & Co Inc | NUCLEIC ACID SEQUENCES CODING TO MGLUR2 AND MGLUR3 FOR NEW POINT MUTATIONS |
| ES2268499T3 (es) | 2002-09-19 | 2007-03-16 | Boehringer Ingelheim (Canada) Ltd. | Inhibidores no nucleosidos de transcriptasa inveresa. |
| AU2003269628A1 (en) | 2002-09-19 | 2004-04-08 | Boehringer Ingelheim (Canada) Ltd. | Non-nucleoside reverse transcriptase inhibitors |
| TW200410975A (en) | 2002-09-26 | 2004-07-01 | Nihon Nohyaku Co Ltd | New pesticide and method for using it, new substituted thienopyrimidine derivative, its intermediate, and method for producing it |
| US7067658B2 (en) | 2002-09-30 | 2006-06-27 | Bristol-Myers Squibb Company | Pyridino and pyrimidino pyrazinones |
| US7998163B2 (en) | 2002-10-03 | 2011-08-16 | Boston Scientific Scimed, Inc. | Expandable retrieval device |
| EP1555324B1 (en) | 2002-10-23 | 2009-12-02 | Daiichi Pure Chemicals Co., Ltd. | Defructosylation method |
| US20040138204A1 (en) | 2002-10-30 | 2004-07-15 | Harrington James Frederick | Compositions and methods for pain reduction |
| US7902203B2 (en) | 2002-11-01 | 2011-03-08 | Abbott Laboratories, Inc. | Anti-infective agents |
| PL376823A1 (pl) | 2002-11-01 | 2006-01-09 | Abbott Laboratories | Środki przeciwzakaźne |
| US6930117B2 (en) | 2002-11-09 | 2005-08-16 | The Procter & Gamble Company | N-alkyl-4-methyleneamino-3-hydroxy-2-pyridones |
| ES2412273T3 (es) | 2002-11-21 | 2013-07-10 | Novartis Ag | Inhibidores de 2-morfolín-4-pirimidinas como inhibidores de fosfotidilinositol (PI) 3-quinasa y su uso en el tratamiento del cáncer. |
| AU2003289386A1 (en) | 2002-12-18 | 2004-07-09 | Takeda Pharmaceutical Company Limited | Jnk inhibitors |
| BR0317714A (pt) * | 2002-12-23 | 2005-11-22 | Hoffmann La Roche | Oxazóis como realçadores de mglur1 |
| CA2511843C (en) | 2002-12-30 | 2012-04-24 | Celgene Corporation | Fluoroalkoxy-substituted 1,3-dihydro-isoindolyl compounds and their pharmaceutical uses |
| KR101078098B1 (ko) | 2003-01-14 | 2011-10-28 | 아레나 파마슈티칼스, 인크. | 대사 조절제로서의 １,２,３-삼치환된 아릴 및 헤테로아릴유도체, 및 당뇨병 및 고혈당증을 비롯한 이에 관련된장애의 예방 및 치료 |
| ITMI20030151A1 (it) | 2003-01-30 | 2004-07-31 | Recordati Ind Chimica E Farma Ceutica S P A | Uso di antagonisti selettivi del recettore mglu5 per il trattamento di disfunzioni neuromuscolari del tratto urinario inferiore. |
| HRP20050663A2 (en) | 2003-02-04 | 2006-12-31 | F. Hoffmann - La Roche Ag | Malonamide derivatives as gamma-secretase inhibitors |
| DE10306250A1 (de) | 2003-02-14 | 2004-09-09 | Aventis Pharma Deutschland Gmbh | Substituierte N-Arylheterozyklen, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| CA2515963A1 (en) | 2003-02-24 | 2004-09-10 | Arena Pharmaceuticals, Inc. | Phenyl- and pyridylpiperidine-derivatives as modulators of glucose metabolism |
| CN100395237C (zh) | 2003-03-03 | 2008-06-18 | 弗·哈夫曼-拉罗切有限公司 | 用作5－ht6调节剂的2,5－取代的四氢异喹啉 |
| ITFI20030058A1 (it) | 2003-03-06 | 2004-09-07 | Univ Firenze | Formulazioni farmaceutiche contenenti tiazolidinedioni |
| DE10311065A1 (de) | 2003-03-13 | 2004-09-23 | Abbott Gmbh & Co. Kg | Pyrimidin-2-on-Verbindungen und ihre therapeutische Verwendung |
| CA2517161C (en) | 2003-03-13 | 2011-08-16 | T. Rad Co., Ltd. | Steam reformer |
| WO2004092123A2 (en) | 2003-04-10 | 2004-10-28 | Microbia, Inc. | Inhibitors of fungal invasion |
| DE602004012083T2 (de) | 2003-04-15 | 2009-04-23 | Astrazeneca Ab | Neue Verbindungen, die als Verstärker von Glutamatrezeptoren dienen |
| JP2004339080A (ja) | 2003-05-13 | 2004-12-02 | Tokyo Institute Of Technology | ピラゾ−ル誘導体を含有する高血圧治療剤 |
| EP1628666B1 (en) | 2003-05-14 | 2015-09-23 | NeuroGenetic Pharmaceuticals, Inc. | Compouds and uses thereof in modulating amyloid beta |
| JP2007504283A (ja) | 2003-05-20 | 2007-03-01 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | β−アミロイド斑に作用物質を結合させる方法 |
| GB0315950D0 (en) | 2003-06-11 | 2003-08-13 | Xention Discovery Ltd | Compounds |
| EP1680125A1 (en) | 2003-07-02 | 2006-07-19 | Warner-Lambert Company LLC | Combination of an allosteric inhibitor of matrix metalloproteinase-13 and a ligand to an alpha-2-delta receptor |
| WO2005007144A2 (en) | 2003-07-14 | 2005-01-27 | Decode Genetics Ehf | Method of diagnosis and treatment for asthma based on haplotype association |
| WO2005021552A1 (en) | 2003-08-29 | 2005-03-10 | Vernalis (Cambridge) Ltd | Pyrimidothiophene compounds |
| GB0320300D0 (en) | 2003-08-29 | 2003-10-01 | Cancer Rec Tech Ltd | Pyrimidothiophene compounds |
| GB0322016D0 (en) | 2003-09-19 | 2003-10-22 | Merck Sharp & Dohme | New compounds |
| US20070197549A1 (en) * | 2004-02-18 | 2007-08-23 | Astrazeneca Ab | Tetrazole compounds and their use as metabotropic glutamate receptor antagonists |
| DE102004009039A1 (de) | 2004-02-23 | 2005-09-08 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 8-[3-Amino-piperidin-1-yl]-xanthine, deren Herstellung und Verwendung als Arzneimittel |
| US7306631B2 (en) | 2004-03-30 | 2007-12-11 | The Procter & Gamble Company | Keratin dyeing compounds, keratin dyeing compositions containing them, and use thereof |
| MXPA06011799A (es) | 2004-04-12 | 2006-12-15 | Sankyo Co | Derivados de tienopiridina. |
| US7459562B2 (en) | 2004-04-23 | 2008-12-02 | Bristol-Myers Squibb Company | Monocyclic heterocycles as kinase inhibitors |
| GB0413605D0 (en) | 2004-06-17 | 2004-07-21 | Addex Pharmaceuticals Sa | Novel compounds |
| US8063004B2 (en) | 2004-07-22 | 2011-11-22 | Malcera, L.L.C. | Chemical composition of matter for the liquefaction and dissolution of asphaltene and paraffin sludges into petroleum crude oils and refined products at ambient temperatures and method of use |
| EP1773792A1 (en) | 2004-07-30 | 2007-04-18 | Merck & Co., Inc. | Indanone potentiators of metabotropic glutamate receptors |
| AU2005269546A1 (en) * | 2004-07-30 | 2006-02-09 | Merck & Co., Inc. | Heterocyclic acetophenone potentiators of metabotropic glutamate receptors |
| AU2005270468A1 (en) | 2004-08-02 | 2006-02-16 | Schwarz Pharma Ag | Indolizine carboxamides and the aza and diaza derivatives thereof |
| JP5276322B2 (ja) | 2004-08-11 | 2013-08-28 | コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ | 虚血性心疾患の超音波診断方法及び装置 |
| TW200613272A (en) | 2004-08-13 | 2006-05-01 | Astrazeneca Ab | Isoindolone compounds and their use as metabotropic glutamate receptor potentiators |
| EP1781655A2 (en) | 2004-08-18 | 2007-05-09 | Pharmacia & Upjohn Company LLC | Triazolopyridine compounds useful for the treatment of inflammation |
| DE102004044884A1 (de) | 2004-09-14 | 2006-05-24 | Grünenthal GmbH | Substituierte bizyklische Imidazo-3-yl-amin-Verbindungen |
| GB0420719D0 (en) | 2004-09-17 | 2004-10-20 | Addex Pharmaceuticals Sa | Novel allosteric modulators |
| GB0420722D0 (en) * | 2004-09-17 | 2004-10-20 | Addex Pharmaceuticals Sa | Novel allosteric modulators |
| AU2005299797A1 (en) | 2004-10-25 | 2006-05-04 | Merck & Co., Inc. | Heterocyclic indanone potentiators of metabotropic glutamate receptors |
| BRPI0518459A2 (pt) | 2004-11-22 | 2008-11-18 | Lilly Co Eli | composto ou um sal farmaceuticamente aceitÁvel do mesmo, composiÇço farmacÊutica, uso de um composto, e, processo para preparar o composto ou um sal farmaceuticamente aceitÁvel do mesmo |
| US7434262B2 (en) | 2004-12-08 | 2008-10-07 | At&T Intellectual Property I, L.P. | Methods and systems that selectively resurrect blocked communications between devices |
| DE102004061288A1 (de) | 2004-12-14 | 2006-06-29 | Schering Ag | 3-Amino-Pyrazolo[3,4b]pyridine als Inhibitoren von Proteintyrosinkinasen, deren Herstellung und Verwendung als Arzneimittel |
| MX2007007220A (es) | 2004-12-27 | 2007-08-20 | Astrazeneca Ab | Compuestos de pirazolona como agonistas de receptor de glutamato metabotropico para el tratamiento de trastornos neurologicos y psiquiatricos. |
| US7456289B2 (en) | 2004-12-31 | 2008-11-25 | National Health Research Institutes | Anti-tumor compounds |
| WO2006091496A2 (en) | 2005-02-24 | 2006-08-31 | Merck & Co., Inc. | Benzazole potentiators of metabotropic glutamate receptors |
| ATE460417T1 (de) | 2005-03-23 | 2010-03-15 | Hoffmann La Roche | Acetylenylpyrazolopyrimidinderivate als mglur2- antagonsten |
| BRPI0607913A2 (pt) | 2005-04-08 | 2010-03-23 | Eisai R&D Man Co Ltd | agente terapÊutico para discinesia |
| US7579360B2 (en) | 2005-06-09 | 2009-08-25 | Bristol-Myers Squibb Company | Triazolopyridine 11-beta hydroxysteroid dehydrogenase type I inhibitors |
| US7572807B2 (en) | 2005-06-09 | 2009-08-11 | Bristol-Myers Squibb Company | Heteroaryl 11-beta-hydroxysteroid dehydrogenase type I inhibitors |
| WO2006137350A1 (ja) | 2005-06-22 | 2006-12-28 | Kissei Pharmaceutical Co., Ltd. | 新規なフロピリジン誘導体、それを含有する医薬組成物およびそれらの用途 |
| RU2008101923A (ru) | 2005-08-05 | 2009-09-10 | Астразенека Аб (Se) | Трициклические бензимидазолы и их применение в качестве модуляторов метаботропного глутаматного рецептора |
| JP5031745B2 (ja) | 2005-08-12 | 2012-09-26 | アストラゼネカ アクチボラグ | 代謝型グルタミン酸受容体増強性イソインドロン |
| WO2007027669A1 (en) | 2005-08-29 | 2007-03-08 | Cps Biofuels, Inc. | Improved biodiesel fuel, additives, and lubbricants |
| CN101268074B (zh) | 2005-09-17 | 2011-09-21 | 斯皮德尔实验股份公司 | 5-氨基-4-羟基-7-（咪唑并[1,2-a]吡啶-6-基甲基）-8-甲基-壬酰胺衍生物和相关用作肾素抑制剂治疗高血压的化合物 |
| EP1764099A3 (en) | 2005-09-17 | 2007-05-09 | Speedel Experimenta AG | Diaminoalcohol derivatives for the treatment of Alzheimer, malaria, HIV |
| US8492428B2 (en) | 2005-09-20 | 2013-07-23 | Mayo Foundation For Medical Education And Research | Small-molecule botulinum toxin inhibitors |
| ES2340321T3 (es) | 2005-09-27 | 2010-06-01 | F.Hoffmann-La Roche Ag | Oxadiazolilpirazolo-pirimidinas, como antagonistas de mglur2. |
| KR101086967B1 (ko) | 2005-11-15 | 2011-11-29 | 어레이 바이오파마 인크. | 과다증식성 질환의 치료를 위한 ｅｒｂｂ 유형 ｉ 수용체티로신 키나제 억제제로서의 ｎ4-페닐-퀴나졸린-4-아민유도체 및 관련 화합물 |
| TW200732313A (en) | 2005-12-15 | 2007-09-01 | Astrazeneca Ab | Oxazolidinone compounds and their use as metabotropic glutamate receptor potentiators |
| TW200804281A (en) | 2006-02-16 | 2008-01-16 | Astrazeneca Ab | New metabotropic glutamate receptor-potentiating isoindolones |
| JP2009528388A (ja) | 2006-03-02 | 2009-08-06 | スミスクライン・ビーチャム・コーポレイション | Ｐｉ３キナーゼ阻害物質として用いられるチアゾロン |
| AR059898A1 (es) * | 2006-03-15 | 2008-05-07 | Janssen Pharmaceutica Nv | Derivados de 3-ciano-piridona 1,4-disustituida y su uso como moduladores alostericos de los receptores mglur2 |
| GB0606774D0 (en) | 2006-04-03 | 2006-05-10 | Novartis Ag | Organic compounds |
| GB0608263D0 (en) | 2006-04-26 | 2006-06-07 | Glaxo Group Ltd | Compounds |
| WO2007135529A2 (en) | 2006-05-23 | 2007-11-29 | Pfizer Products Inc. | Azabenzimidazolyl compounds as mglur2 potentiators |
| WO2007135527A2 (en) | 2006-05-23 | 2007-11-29 | Pfizer Products Inc. | Benzimidazolyl compounds |
| CA2655573C (en) | 2006-06-19 | 2014-04-29 | Toray Industries, Inc. | Therapeutic or prophylactic agent for multiple sclerosis |
| US20100035756A1 (en) | 2006-07-12 | 2010-02-11 | Syngenta Limited | Triazolophyridine derivatives as herbicides |
| US8217177B2 (en) | 2006-07-14 | 2012-07-10 | Amgen Inc. | Fused heterocyclic derivatives and methods of use |
| US8198448B2 (en) | 2006-07-14 | 2012-06-12 | Amgen Inc. | Fused heterocyclic derivatives and methods of use |
| PE20080403A1 (es) | 2006-07-14 | 2008-04-25 | Amgen Inc | Derivados heterociclicos fusionados y metodos de uso |
| WO2008012623A1 (en) | 2006-07-25 | 2008-01-31 | Pfizer Products Inc. | Benzimidazolyl compounds as potentiators of mglur2 subtype of glutamate receptor |
| WO2008012622A2 (en) | 2006-07-25 | 2008-01-31 | Pfizer Products Inc. | Azabenzimidazolyl compounds as potentiators of mglur2 subtype of glutamate receptor |
| CN101511802A (zh) | 2006-09-13 | 2009-08-19 | 阿斯利康(瑞典)有限公司 | 螺唑烷酮化合物及其作为代谢型谷氨酸受体增效剂的用途 |
| AU2007307031B2 (en) | 2006-10-11 | 2011-11-24 | Amgen Inc. | Imidazo- and triazolo-pyridine compounds and methods of use therof |
| EP2089389A2 (en) | 2006-11-01 | 2009-08-19 | Bristol-Myers Squibb Company | Heterocyclic compounds as modulators of glucocorticoid receptor, ap-1, and/or nf-kappa-b activity |
| TW200831085A (en) | 2006-12-13 | 2008-08-01 | Merck & Co Inc | Non-nucleoside reverse transcriptase inhibitors |
| MX2009006706A (es) | 2006-12-22 | 2009-07-02 | Astex Therapeutics Ltd | Compuestos heterociclicos biciclicos como inhibidores del receptor del factor de crecimiento de fibroblastos. |
| MX2009006704A (es) | 2006-12-22 | 2009-06-30 | Astex Therapeutics Ltd | Derivados de amina triciclicos como inhibidores de proteina de tirosina cinasa. |
| WO2008100715A1 (en) | 2007-02-09 | 2008-08-21 | Astrazeneca Ab | Aza-isoindolones and their use as metabotropic glutamate receptor potentiators - 613 |
| ES2320955B1 (es) | 2007-03-02 | 2010-03-16 | Laboratorios Almirall S.A. | Nuevos derivados de 3-((1,2,4)triazolo(4,3-a)piridin-7-il)benzamida. |
| TW200845978A (en) | 2007-03-07 | 2008-12-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives |
| BRPI0808776A2 (pt) | 2007-03-07 | 2014-08-19 | Janssen Pharmaceutica Nv | Fenóxi amino tiazolonas substituídas como moduladores de receptor-alfa relacionado a estrogênio |
| NZ579372A (en) | 2007-03-07 | 2012-02-24 | Janssen Pharmaceutica Nv | Substituted phenoxy thiazolidinediones as estrogen related receptor-alpha modulators |
| WO2008109731A2 (en) | 2007-03-07 | 2008-09-12 | Jassen Pharmaceutica N.V. | Substituted phenoxy n-alkylated thiazoledinedione as estrogen related receptor-alpha modulators |
| TW200900065A (en) | 2007-03-07 | 2009-01-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-pyridinyloxy-phenyl)-pyridin-2-one derivatives |
| AR065622A1 (es) | 2007-03-07 | 2009-06-17 | Ortho Mcneil Janssen Pharm | Derivados de 3-ciano -4- (4-fenil- piperidin -1- il) piridin -2- ona |
| GB0704407D0 (en) | 2007-03-07 | 2007-04-18 | Glaxo Group Ltd | Compounds |
| CA2680262C (en) | 2007-03-09 | 2012-11-13 | Sanofi-Aventis | Substituted dihydro and tetrahydro oxazolopyrimidinones, preparation and use thereof |
| WO2008124085A2 (en) | 2007-04-03 | 2008-10-16 | Exelixis, Inc. | Methods of using combinations of mek and jak-2 inhibitors |
| WO2008130853A1 (en) | 2007-04-17 | 2008-10-30 | Astrazeneca Ab | Hydrazides and their use as metabotropic glutamate receptor potentiators - 681 |
| NZ581127A (en) | 2007-05-25 | 2012-06-29 | Abbott Gmbh & Co Kg | Heterocyclic compounds as positive modulators of metabotropic glutamate receptor 2 (mglu2 receptor) |
| TWI417100B (zh) | 2007-06-07 | 2013-12-01 | Astrazeneca Ab | 二唑衍生物及其作為代謝型麩胺酸受體增效劑-８４２之用途 |
| TW200911255A (en) | 2007-06-07 | 2009-03-16 | Astrazeneca Ab | Metabotropic glutamate receptor oxadiazole ligands and their use as potentiators-841 |
| WO2009004430A1 (en) | 2007-06-29 | 2009-01-08 | Pfizer Inc. | N-benzyl oxazolidinones and related heterocycleic compounds as potentiators of glutamate receptors |
| BRPI0817101A2 (pt) | 2007-09-14 | 2017-05-09 | Addex Pharmaceuticals Sa | 4-(aril-x-fenil)-1h-piridin-2-onas 1,3-dissubstituídas |
| SI2203439T1 (sl) | 2007-09-14 | 2011-05-31 | Ortho Mcneil Janssen Pharm | 1',3'-disubstituirani 4-fenil-3,4,5,6-tetrahidro-2H-1'H-(1,4')bipiridinil-2'-oni |
| ES2409215T3 (es) | 2007-09-14 | 2013-06-25 | Janssen Pharmaceuticals, Inc. | 4-fenil-1H-piridin-2-onas 1-3-disustituidas |
| US8119658B2 (en) | 2007-10-01 | 2012-02-21 | Bristol-Myers Squibb Company | Triazolopyridine 11-beta hydroxysteroid dehydrogenase type I inhibitors |
| ES2637794T3 (es) | 2007-11-14 | 2017-10-17 | Janssen Pharmaceuticals, Inc. | Derivados de imidazo[1,2-A]piridina y su uso como moduladores alostéricos positivos de receptores MGLUR2 |
| US20100292241A1 (en) | 2008-01-24 | 2010-11-18 | Merck Sharp & Dohme Corp. | 3,5-substituted-1,3-oxazolidin-2-one derivatives |
| JP5309162B2 (ja) | 2008-03-06 | 2013-10-09 | サノフイ | 置換されたジヒドロ、トリヒドロ及びテトラヒドロシクロアルキルオキサゾロピリミジノン、その製造及び使用 |
| DE102008001056A1 (de) | 2008-04-08 | 2009-10-15 | Robert Bosch Gmbh | Umlenkeinrichtung für einen Strahl einer elektromagnetischen Welle |
| EP2291078A4 (en) | 2008-05-15 | 2011-08-24 | Merck Sharp & Dohme | OXAZOLBENZIMIDAZOLDERIVATE |
| AU2009246629A1 (en) | 2008-05-15 | 2009-11-19 | Merck Sharp & Dohme Corp. | Oxazolobenzimidazole derivatives |
| US7790760B2 (en) | 2008-06-06 | 2010-09-07 | Astrazeneca Ab | Metabotropic glutamate receptor isoxazole ligands and their use as potentiators 286 |
| TW201006801A (en) | 2008-07-18 | 2010-02-16 | Lilly Co Eli | Imidazole carboxamides |
| US20100037487A1 (en) | 2008-08-14 | 2010-02-18 | Susan Connett | Method and apparatus for sandal with hidden strap adjustment |
| UY32049A (es) | 2008-08-14 | 2010-03-26 | Takeda Pharmaceutical | Inhibidores de cmet |
| TWI496779B (zh) | 2008-08-19 | 2015-08-21 | Array Biopharma Inc | 作為ｐｉｍ激酶抑制劑之三唑吡啶化合物 |
| US8557809B2 (en) | 2008-08-19 | 2013-10-15 | Array Biopharma Inc. | Triazolopyridine compounds as PIM kinase inhibitors |
| ES2439291T3 (es) | 2008-09-02 | 2014-01-22 | Janssen Pharmaceuticals, Inc. | Derivados de 3-azabiciclo[3.1.0]hexilo como moduladores de receptores de glutamato metabotrópicos |
| CA2738849C (en) | 2008-10-16 | 2016-06-28 | Addex Pharma S.A. | Indole and benzomorpholine derivatives as modulators of metabotropic glutamate receptors |
| ES2401691T3 (es) | 2008-11-28 | 2013-04-23 | Ortho-Mcneil-Janssen Pharmaceuticals, Inc. | Derivados de indol y de benzoxacina como moduladores de los receptores metabotrópicos de glutamato |
| AT507619B1 (de) | 2008-12-05 | 2011-11-15 | Oesterreichisches Forschungs Und Pruefzentrum Arsenal Ges M B H | Verfahren zur approximation des zeitlichen verlaufs von verkehrsdaten |
| EP2393807B1 (en) | 2009-02-04 | 2013-08-14 | Boehringer Ingelheim International GmbH | Cyclic inhibitors of 11 -hydroxysteroid dehydrogenase 1 |
| WO2010114726A1 (en) | 2009-03-31 | 2010-10-07 | Merck Sharp & Dohme Corp. | Aminobenzotriazole derivatives |
| US8685967B2 (en) | 2009-04-07 | 2014-04-01 | Merck Sharp & Dohme Corp. | Substituted triazolopyridines and analogs thereof |
| MY153913A (en) | 2009-05-12 | 2015-04-15 | Janssen Pharmaceuticals Inc | 7-aryl-1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
| ES2440001T3 (es) | 2009-05-12 | 2014-01-27 | Janssen Pharmaceuticals, Inc. | Derivados de 1,2,4-triazolo[4,3-A]piridina y su uso para el tratamiento o prevención de trastornos neurológicos y psiquiátricos |
| SG176018A1 (en) | 2009-05-12 | 2011-12-29 | Janssen Pharmaceuticals Inc | 1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
| WO2010141360A1 (en) | 2009-06-05 | 2010-12-09 | Merck Sharp & Dohme Corp. | Biaryl benzotriazole derivatives |
| WO2011022312A1 (en) | 2009-08-20 | 2011-02-24 | Merck Sharp & Dohme Corp. | Ether benzotriazole derivatives |
| CN102002040A (zh) | 2009-09-01 | 2011-04-06 | 上海药明康德新药开发有限公司 | 一种三唑并吡啶环化合物的合成方法 |
| AR078173A1 (es) | 2009-09-15 | 2011-10-19 | Sanofi Aventis | Bifeniloximetil dihidro oxazolopirimidinonas sustituidas, su preparacion y su uso |
| AR078172A1 (es) | 2009-09-15 | 2011-10-19 | Sanofi Aventis | Fenoximetil dihidro oxazolopirimidinonas sustituidas y uso de las mismas como moduladores de receptores metabotropicos de mglur |
| AR078171A1 (es) | 2009-09-15 | 2011-10-19 | Sanofi Aventis | Dihidrobenzocicloalquiloximetil-oxazolopirimidinonas sustituidas, preparacion y uso de las mismas |
| WO2011034741A1 (en) | 2009-09-15 | 2011-03-24 | Merck Sharp & Dohme Corp. | Imidazopyridin-2-one derivatives |
| JP5204071B2 (ja) | 2009-09-25 | 2013-06-05 | パナソニック株式会社 | 電気かみそり |
| EP2496569A2 (en) | 2009-11-02 | 2012-09-12 | MSD Oss B.V. | Heterocyclic derivatives |
| AU2011223898A1 (en) | 2010-03-04 | 2012-09-13 | Merck Sharp & Dohme Corp. | Positive allosteric modulators of mGluR2 |
| US8748632B2 (en) | 2010-03-19 | 2014-06-10 | Sanford-Burnham Medical Research Institute | Positive allosteric modulators of group II mGluRs |
| US8314120B2 (en) | 2010-03-30 | 2012-11-20 | Abbott Gmbh & Co. Kg | Small molecule potentiators of metabotropic glutamate receptors |
| US8664214B2 (en) | 2010-03-30 | 2014-03-04 | AbbVie Deutschland GmbH & Co. KG | Small molecule potentiators of metabotropic glutamate receptors I |
| US20130035332A1 (en) | 2010-04-29 | 2013-02-07 | Layton Mark E | Substituted 1,3-Benzothiazol-2(3H)-Ones and [1,3]Thiazolo[5,4-B]Pyridin-2(IH)-Ones as Positive Allosteric Modulators of MGLUR2 |
| JP2013525427A (ja) | 2010-04-30 | 2013-06-20 | アストラゼネカ・アクチエボラーグ | 代謝調節型グルタミン酸受容体ポジティブアロステリックモジュレーターの多形 |
| US8765784B2 (en) | 2010-06-09 | 2014-07-01 | Merck Sharp & Dohme Corp. | Positive allosteric modulators of MGLUR2 |
| CN101893589B (zh) | 2010-06-29 | 2012-10-17 | 中国人民解放军第三0二医院 | 一种无菌检查方法及其使用的全封闭集菌安瓿培养器 |
| WO2012021382A1 (en) | 2010-08-12 | 2012-02-16 | Merck Sharp & Dohme Corp. | Positive allosteric modulators of mglur2 |
| US8785481B2 (en) | 2010-09-29 | 2014-07-22 | Merck Sharp & Dohme Corp. | Ether benzotriazole derivatives |
| CA2814998C (en) | 2010-11-08 | 2019-10-29 | Janssen Pharmaceuticals, Inc. | 1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
| ES2552455T3 (es) | 2010-11-08 | 2015-11-30 | Janssen Pharmaceuticals, Inc. | Derivados de 1,2,4-triazolo[4,3-a]piridina y su uso como moduladores alostéricos positivos de receptores mGluR2 |
| CN103298809B (zh) | 2010-11-08 | 2016-08-31 | 杨森制药公司 | 1,2,4-三唑并[4,3-a]吡啶衍生物及其作为MGLUR2受体的正变构调节剂的用途 |
| AU2011328196A1 (en) | 2010-11-08 | 2013-05-02 | Janssen Pharmaceuticals, Inc. | Radiolabelled mGluR2 PET ligands |
| US9139576B2 (en) | 2011-05-03 | 2015-09-22 | Merck Sharp & Dohme Corp. | Aminomethyl biaryl benzotriazole derivatives |
| US20140088151A1 (en) | 2011-05-03 | 2014-03-27 | Douglas C. Beshore | Alhydroxymethyl biaryl benzotriazole derivatives |
| WO2012151139A1 (en) | 2011-05-03 | 2012-11-08 | Merck Sharp & Dohme Corp. | Alkyne benzotriazole derivatives |
-
2008
- 2008-03-06 TW TW097107754A patent/TW200845978A/zh unknown
- 2008-03-07 NZ NZ579988A patent/NZ579988A/en not_active IP Right Cessation
- 2008-03-07 BR BRPI0808509-9A patent/BRPI0808509A2/pt not_active IP Right Cessation
- 2008-03-07 PL PL08717515T patent/PL2134708T3/pl unknown
- 2008-03-07 WO PCT/EP2008/052768 patent/WO2008107481A1/en not_active Ceased
- 2008-03-07 KR KR1020097020927A patent/KR20090125814A/ko not_active Withdrawn
- 2008-03-07 AR ARP080100961A patent/AR065654A1/es not_active Application Discontinuation
- 2008-03-07 JP JP2009552216A patent/JP5357061B2/ja not_active Expired - Fee Related
- 2008-03-07 EA EA200901160A patent/EA017294B1/ru not_active IP Right Cessation
- 2008-03-07 AT AT08717515T patent/ATE509020T1/de active
- 2008-03-07 AU AU2008223796A patent/AU2008223796B2/en not_active Ceased
- 2008-03-07 CA CA2680104A patent/CA2680104C/en not_active Expired - Fee Related
- 2008-03-07 EP EP08717515A patent/EP2134708B1/en active Active
- 2008-03-07 CN CN2008800073170A patent/CN101711244B/zh not_active Expired - Fee Related
- 2008-03-07 DK DK08717515.4T patent/DK2134708T3/da active
- 2008-03-07 US US12/529,568 patent/US8906939B2/en not_active Expired - Fee Related
- 2008-03-07 MX MX2009009424A patent/MX2009009424A/es active IP Right Grant
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- 2009-08-11 IL IL200329A patent/IL200329A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO2008107481A8 (en) | 2008-12-24 |
| TW200845978A (en) | 2008-12-01 |
| CN101711244A (zh) | 2010-05-19 |
| WO2008107481A1 (en) | 2008-09-12 |
| DK2134708T3 (da) | 2011-08-29 |
| IL200329A0 (en) | 2010-04-29 |
| MX2009009424A (es) | 2010-02-09 |
| AR065654A1 (es) | 2009-06-24 |
| ATE509020T1 (de) | 2011-05-15 |
| BRPI0808509A2 (pt) | 2014-08-19 |
| EP2134708A1 (en) | 2009-12-23 |
| US8906939B2 (en) | 2014-12-09 |
| EA200901160A1 (ru) | 2010-04-30 |
| KR20090125814A (ko) | 2009-12-07 |
| EA017294B1 (ru) | 2012-11-30 |
| CN101711244B (zh) | 2013-01-16 |
| JP2010520265A (ja) | 2010-06-10 |
| US20100087487A1 (en) | 2010-04-08 |
| EP2134708B1 (en) | 2011-05-11 |
| PL2134708T3 (pl) | 2011-10-31 |
| JP5357061B2 (ja) | 2013-12-04 |
| NZ579988A (en) | 2011-09-30 |
| AU2008223796B2 (en) | 2011-03-17 |
| AU2008223796A1 (en) | 2008-09-12 |
| CA2680104A1 (en) | 2008-09-12 |
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