NO326830B1 - 2,4,8-trisubstituerte -8H-pyrido[2,3-d]pyrimidin-7-on-forbindelser, fremgangsmater for fremstilling derav, anvendelse derav, farmasoytiske preparater inneholdelde forbindelsene samt intermediater - Google Patents
2,4,8-trisubstituerte -8H-pyrido[2,3-d]pyrimidin-7-on-forbindelser, fremgangsmater for fremstilling derav, anvendelse derav, farmasoytiske preparater inneholdelde forbindelsene samt intermediater Download PDFInfo
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- NO326830B1 NO326830B1 NO20031794A NO20031794A NO326830B1 NO 326830 B1 NO326830 B1 NO 326830B1 NO 20031794 A NO20031794 A NO 20031794A NO 20031794 A NO20031794 A NO 20031794A NO 326830 B1 NO326830 B1 NO 326830B1
- Authority
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- Norway
- Prior art keywords
- phenyl
- fluoro
- pyrido
- methyl
- pyrimidin
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Classifications
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- 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
-
- 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
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Families Citing this family (95)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1112070B1 (en) * | 1998-08-20 | 2004-05-12 | Smithkline Beecham Corporation | Novel substituted triazole compounds |
US7235551B2 (en) * | 2000-03-02 | 2007-06-26 | Smithkline Beecham Corporation | 1,5-disubstituted-3,4-dihydro-1h-pyrimido[4,5-d]pyrimidin-2-one compounds and their use in treating csbp/p38 kinase mediated diseases |
EP1333833B1 (en) * | 2000-10-23 | 2011-08-24 | GlaxoSmithKline LLC | Novel trisubstituted-8H-pyrido[2,3-d]pyrimidin-7-one compound for the treatment of CSBP/p38 kinase mediated diseases |
WO2002058695A1 (en) * | 2000-12-20 | 2002-08-01 | Merck & Co., Inc. | (halo-benzo carbonyl)heterocyclo fused phenyl p38 kinase inhibiting agents |
ATE485275T1 (de) | 2002-02-12 | 2010-11-15 | Glaxosmithkline Llc | Nicotinamide und deren verwendung als p38 inhibitoren |
BR0309053A (pt) | 2002-04-19 | 2005-02-22 | Smithkline Beecham Corp | Compostos |
US8293751B2 (en) | 2003-01-14 | 2012-10-23 | Arena Pharmaceuticals, Inc. | 1,2,3-trisubstituted aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto such as diabetes and hyperglycemia |
CN100372851C (zh) | 2003-05-05 | 2008-03-05 | 弗·哈夫曼-拉罗切有限公司 | 具有crf活性的稠合的嘧啶衍生物 |
CN1560035A (zh) * | 2004-03-12 | 2005-01-05 | 沈阳药科大学 | 5-羟基吲哚-3-羧酸脂类衍生物 |
CA2590294A1 (en) * | 2004-12-13 | 2006-06-22 | Sunesis Pharmaceuticals, Inc. | Pyrido pyrimidinones, dihydro pyrimido pyrimidinones and pteridinones useful as raf kinase inhibitors |
US8017395B2 (en) | 2004-12-17 | 2011-09-13 | Lifescan, Inc. | Seeding cells on porous supports |
US7842809B2 (en) * | 2005-01-24 | 2010-11-30 | Bayer Schering Pharma Ag | Pyrazolopyridines and salts thereof, a pharmaceutical composition comprising said compounds, a method of preparing same and use of same |
TW200724142A (en) | 2005-03-25 | 2007-07-01 | Glaxo Group Ltd | Novel compounds |
AR053346A1 (es) * | 2005-03-25 | 2007-05-02 | Glaxo Group Ltd | Compuesto derivado de 8h -pirido (2,3-d) pirimidin -7 ona 2,4,8- trisustituida composicion farmaceutica y uso para preparar una composicion para tratamiento y profilxis de una enfermedad mediada por la quinasa csbp/ rk/p38 |
CN101495475A (zh) * | 2005-03-25 | 2009-07-29 | 葛兰素集团有限公司 | 制备吡啶并[2,3-d]嘧啶-7-酮和3,4-二氢嘧啶并[4,5-d]嘧啶-2(1H)-酮衍生物的方法 |
JP2008535822A (ja) * | 2005-03-25 | 2008-09-04 | グラクソ グループ リミテッド | 新規化合物 |
WO2006118914A2 (en) * | 2005-04-29 | 2006-11-09 | Children's Medical Center Corporation | Methods of increasing proliferation of adult mammalian cardiomyocytes through p38 map kinase inhibition |
CA2608405A1 (en) * | 2005-05-17 | 2006-11-23 | Schering Corporation | Heterocycles as nicotinic acid receptor agonists for the treatment of dyslipidemia |
AU2006202209B2 (en) | 2005-05-27 | 2011-04-14 | Lifescan, Inc. | Amniotic fluid derived cells |
CN101484575B (zh) * | 2005-06-08 | 2013-10-02 | 森托科尔公司 | 用于眼变性的细胞疗法 |
PE20070823A1 (es) * | 2005-11-15 | 2007-08-09 | Glaxo Group Ltd | Sal tosilato de 8-(2,6-difluorofenil)-4-(4-fluoro-2-metilfenil)-2-{[2-hidroxi-1-(hidroximetil)etil]amino}pirido[2,3-]pirimidin-7(8h)-ona |
US20070122448A1 (en) * | 2005-11-28 | 2007-05-31 | Alireza Rezania | Compositions and methods to create a vascularized environment for cellular transplantation |
US8741643B2 (en) | 2006-04-28 | 2014-06-03 | Lifescan, Inc. | Differentiation of pluripotent stem cells to definitive endoderm lineage |
AU2007244675A1 (en) | 2006-04-28 | 2007-11-08 | Lifescan, Inc. | Differentiation of human embryonic stem cells |
JP2009542817A (ja) * | 2006-06-16 | 2009-12-03 | グラクソ グループ リミテッド | 新規化合物 |
JP2009542816A (ja) * | 2006-06-16 | 2009-12-03 | グラクソ グループ リミテッド | 新規化合物 |
US20090318424A1 (en) * | 2006-06-16 | 2009-12-24 | Mauro Corsi | Novel compounds |
PL2050749T3 (pl) | 2006-08-08 | 2018-03-30 | Chugai Seiyaku Kabushiki Kaisha | Pochodna pirymidyny jako inhibitor pi3k i jej zastosowanie |
GB0621830D0 (en) * | 2006-11-02 | 2006-12-13 | Chroma Therapeutics Ltd | Inhibitors of p38 mitogen-activated protein kinase |
JO2985B1 (ar) | 2006-12-20 | 2016-09-05 | Takeda Pharmaceuticals Co | مثبطات كينازmapk/erk |
EP2126045A4 (en) * | 2007-01-30 | 2010-05-26 | Univ Georgia | EARLY MESODERM CELLS, STABLE POPULATION OF MESENDODERM CELLS WITH THE ABILITY TO GENERATE ENDODERM AND MESODERM CELL LINES AND MULTIPOTENTIAL MIGRATION CELLS |
BRPI0813787A2 (pt) | 2007-07-01 | 2014-10-07 | Lifescan Inc | Cultura de célula-tronco pluripotente isolada |
US9080145B2 (en) * | 2007-07-01 | 2015-07-14 | Lifescan Corporation | Single pluripotent stem cell culture |
CA2693156C (en) | 2007-07-18 | 2018-03-06 | Alireza Rezania | Differentiation of human embryonic stem cells |
RU2473685C2 (ru) | 2007-07-31 | 2013-01-27 | Лайфскен, Инк. | Дифференцировка человеческих эмбриональных стволовых клеток |
ATE523585T1 (de) * | 2007-11-27 | 2011-09-15 | Lifescan Inc | Differenzierung menschlicher embryonaler stammzellen |
KR20190057164A (ko) | 2008-02-21 | 2019-05-27 | 얀센 바이오테크 인코포레이티드 | 세포 부착, 배양 및 탈리를 위한 방법, 표면 개질 플레이트 및 조성물 |
US8623648B2 (en) | 2008-04-24 | 2014-01-07 | Janssen Biotech, Inc. | Treatment of pluripotent cells |
JP5734183B2 (ja) * | 2008-06-30 | 2015-06-17 | ヤンセン バイオテツク,インコーポレーテツド | 多能性幹細胞の分化 |
CN102165058B (zh) | 2008-07-25 | 2015-07-01 | 佐治亚大学研究基金会 | 中胚层来源的ISL 1+多潜能细胞(IMPs)的组合物、心外膜祖细胞(EPCs)和多潜能CXCR4+CD56+细胞(C56Cs)及其使用方法 |
US20110305672A1 (en) | 2008-07-25 | 2011-12-15 | University Of Georgia Research Foundation, Inc. | COMPOSITIONS FOR MESODERM DERIVED ISL1+ MULTIPOTENT CELLS (IMPs), EPICARDIAL PROGENITOR CELLS (EPCs) AND MULTIPOTENT CD56C CELLS (C56Cs) AND METHODS OF PRODUCING AND USING SAME |
US20100028307A1 (en) * | 2008-07-31 | 2010-02-04 | O'neil John J | Pluripotent stem cell differentiation |
RU2528861C2 (ru) * | 2008-10-31 | 2014-09-20 | Сентокор Орто Байотек Инк. | Дифференцирование человеческих эмбриональных стволовых клеток в линию панкреатических эндокринных клеток |
CN102272291B (zh) * | 2008-10-31 | 2018-01-16 | 詹森生物科技公司 | 人胚胎干细胞向胰腺内分泌谱系的分化 |
RU2547925C2 (ru) * | 2008-11-20 | 2015-04-10 | Сентокор Орто Байотек Инк. | Способы и композиции для закрепления и культивирования клеток на плоских носителях |
BRPI0920956A2 (pt) | 2008-11-20 | 2015-08-18 | Centocor Ortho Biotech Inc | Cultura de células-tronco pluripotentes em microveículos |
US8741910B2 (en) | 2008-11-25 | 2014-06-03 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase activators |
US20100260825A1 (en) * | 2009-04-13 | 2010-10-14 | Nair Madhavan G | Antifolates for the treatment of cardiovascular, inflammatory, neoplastic, autoimmune and related diseases in sublingual dosage units, film strips, or skin patches |
SG177416A1 (en) | 2009-07-20 | 2012-02-28 | Janssen Biotech Inc | Differentiation of human embryonic stem cells |
GB2485112B (en) * | 2009-07-20 | 2014-02-26 | Janssen Biotech Inc | Differentiation of human embryonic stem cells |
WO2011011300A2 (en) | 2009-07-20 | 2011-01-27 | Centocor Ortho Biotech Inc. | Differentiation of human embryonic stem cells |
AR078805A1 (es) | 2009-10-29 | 2011-12-07 | Centocor Ortho Biotech Inc | Celulas madre pluripotentes |
ES2633648T3 (es) * | 2009-12-23 | 2017-09-22 | Janssen Biotech, Inc. | Diferenciación de células madre embrionarias humanas |
RU2701335C2 (ru) | 2009-12-23 | 2019-09-25 | Янссен Байотек, Инк. | Способ получения популяции панкреатических эндокринных клеток, соэкспрессирующих nkx6.1 и инсулин, и способ лечения диабета |
CA2791476C (en) | 2010-03-01 | 2020-06-30 | Janssen Biotech, Inc. | Methods for purifying cells derived from pluripotent stem cells |
RU2663339C1 (ru) | 2010-05-12 | 2018-08-03 | Янссен Байотек, Инк. | Дифференцирование эмбриональных стволовых клеток человека |
PE20130779A1 (es) | 2010-07-09 | 2013-06-21 | Bayer Ip Gmbh | Pirimidinas y triazinas condensadas y su uso |
WO2012021698A2 (en) | 2010-08-12 | 2012-02-16 | Janssen Biotech, Inc. | Treatment of diabetes with pancreatic endocrine precursor cells |
CN103221536B (zh) | 2010-08-31 | 2016-08-31 | 詹森生物科技公司 | 人胚胎干细胞的分化 |
EP2611907B1 (en) | 2010-08-31 | 2016-05-04 | Janssen Biotech, Inc. | Differentiation of pluripotent stem cells |
PL2611910T3 (pl) | 2010-08-31 | 2018-06-29 | Janssen Biotech, Inc | Różnicowanie ludzkich embrionalnych komórek macierzystych |
BR112013008100A2 (pt) | 2010-09-22 | 2016-08-09 | Arena Pharm Inc | "moduladores do receptor de gpr19 e o tratamento de distúrbios relacionados a eles." |
CN103476769B (zh) | 2010-10-27 | 2016-06-01 | 沃尔特及伊莱萨霍尔医学研究院 | 抗癌剂 |
JP6139410B2 (ja) | 2010-12-02 | 2017-05-31 | テクニオン リサーチ アンド ディベロップメント ファウンデーション リミテッド | 角膜細胞の作製方法および該角膜細胞を含む細胞集団 |
US9404087B2 (en) | 2010-12-15 | 2016-08-02 | Kadimastem Ltd. | Insulin producing cells derived from pluripotent stem cells |
CA2833698A1 (en) | 2011-04-21 | 2012-10-26 | Bayer Intellectual Property Gmbh | Fluoroalkyl-substituted pyrazolopyridines and use thereof |
EP2794857A4 (en) | 2011-12-22 | 2015-07-08 | Janssen Biotech Inc | DIFFERENTIATION OF HUMAN EMBRYONIC STEM CELLS IN SINGLE INSULIN POSITIVE CELLS |
DE102012200360A1 (de) | 2012-01-11 | 2013-07-11 | Bayer Intellectual Property Gmbh | Substituierte Triazine und ihre Verwendung |
DE102012200349A1 (de) | 2012-01-11 | 2013-07-11 | Bayer Intellectual Property Gmbh | Substituierte annellierte Pyrimidine und Triazine und ihre Verwendung |
EP2822951B1 (de) | 2012-03-06 | 2017-07-26 | Bayer Intellectual Property GmbH | Substituierte azabicyclen und ihre verwendung |
CA2866590A1 (en) | 2012-03-07 | 2013-09-12 | Janssen Biotech, Inc. | Defined media for expansion and maintenance of pluripotent stem cells |
EP3450542B1 (en) | 2012-06-08 | 2021-09-01 | Janssen Biotech, Inc. | Differentiation of human embryonic stem cells into pancreatic endocrine cells |
RU2658488C2 (ru) | 2012-12-31 | 2018-06-21 | Янссен Байотек, Инк. | Способ получения клеток, экспрессирующих маркеры, характерные для панкреатических эндокринных клеток |
US10370644B2 (en) | 2012-12-31 | 2019-08-06 | Janssen Biotech, Inc. | Method for making human pluripotent suspension cultures and cells derived therefrom |
WO2014106141A1 (en) | 2012-12-31 | 2014-07-03 | Janssen Biotech, Inc. | Suspension and clustering of human pluripotent cells for differentiation into pancreatic endocrine cells |
CA2896658C (en) | 2012-12-31 | 2021-06-22 | Janssen Biotech, Inc. | Differentiation of human embryonic stem cells into pancreatic endocrine cells using hb9 regulators |
KR20150121007A (ko) | 2013-03-01 | 2015-10-28 | 바이엘 파마 악티엔게젤샤프트 | 트리플루오르메틸-치환된 고리-융합된 피리미딘 및 그의 용도 |
EP2972193B1 (en) | 2013-03-13 | 2019-12-18 | University Of Miami | Method for isolation and purification of microvesicles from cell culture supernatants and biological fluids |
MX2016000258A (es) | 2013-07-10 | 2016-04-28 | Bayer Pharma AG | Bencil-1h-pirazolo[3,4-b]piridinas y su uso. |
KR102162138B1 (ko) | 2014-05-16 | 2020-10-06 | 얀센 바이오테크 인코포레이티드 | 췌장 내분비 세포에서 mafa 발현을 향상시키기 위한 소분자의 용도 |
CN116850181A (zh) | 2015-01-06 | 2023-10-10 | 艾尼纳制药公司 | 治疗与s1p1受体有关的病症的方法 |
MX2017016530A (es) | 2015-06-22 | 2018-03-12 | Arena Pharm Inc | Sal cristalina de l-arginina del acido (r)-2-(7-(4-ciclopentil-3-( trifluorometil)benciloxi)-1,2,3,4-tetrahidrociclopenta[b]indol-3- il)acetico (compuesto1) para ser utilizada en transtornos asociados con el receptor de esfingosina-1-fosfato 1 (s1p1). |
JP6394547B2 (ja) * | 2015-09-18 | 2018-09-26 | トヨタ自動車株式会社 | 車両制御装置 |
WO2017094001A1 (en) | 2015-11-30 | 2017-06-08 | Kadimastem Ltd | Methods for differentiating and purifying pancreatic endocrine cells |
WO2017151409A1 (en) | 2016-02-29 | 2017-09-08 | University Of Florida Research Foundation, Incorporated | Chemotherapeutic methods |
MA45479A (fr) | 2016-04-14 | 2019-02-20 | Janssen Biotech Inc | Différenciation de cellules souches pluripotentes en cellules de l'endoderme de l'intestin moyen |
CN110520124A (zh) | 2017-02-16 | 2019-11-29 | 艾尼纳制药公司 | 用于治疗原发性胆汁性胆管炎的化合物和方法 |
US10342786B2 (en) | 2017-10-05 | 2019-07-09 | Fulcrum Therapeutics, Inc. | P38 kinase inhibitors reduce DUX4 and downstream gene expression for the treatment of FSHD |
WO2019071147A1 (en) | 2017-10-05 | 2019-04-11 | Fulcrum Therapeutics, Inc. | INHIBITORS OF KINASE P38 REDUCING EXPRESSION OF DUX4 GENE AND DOWNSTREAM GENES FOR THE TREATMENT OF FSHD |
GB201721793D0 (en) | 2017-12-22 | 2018-02-07 | Hvivo Services Ltd | Methods and compunds for the treatment or prevention of hypercytokinemia and severe influenza |
TW202112368A (zh) | 2019-06-13 | 2021-04-01 | 荷蘭商法西歐知識產權股份有限公司 | 用於治療有關dux4表現之疾病的抑制劑組合 |
US11697648B2 (en) | 2019-11-26 | 2023-07-11 | Theravance Biopharma R&D Ip, Llc | Fused pyrimidine pyridinone compounds as JAK inhibitors |
WO2021202990A2 (en) * | 2020-04-03 | 2021-10-07 | TEPPER, Mark, Allan | Methods for the treatment of betacoronavirus infections |
IL300393A (en) | 2020-08-21 | 2023-04-01 | Univ Miami | Preparations and treatment methods using microvesicles from mesenchymal stem cells derived from bone marrow |
WO2023205158A1 (en) | 2022-04-19 | 2023-10-26 | University Of Miami | Compositions comprising microvesicles for use in the prevention and treatment of graft versus host disease |
Family Cites Families (149)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2833779A (en) | 1956-10-29 | 1958-05-06 | American Cyanamid Co | Substituted pyrazoles |
US3910913A (en) | 1969-11-04 | 1975-10-07 | American Home Prod | 4,5-Diamino-7H-pyrrolo{8 2,3-d{9 pyrimidine derivatives |
US3631045A (en) | 1969-11-04 | 1971-12-28 | American Home Prod | 4 5-diamino-7h-pyrrolo(2 3-d)pyrimidine derivatives |
US3795674A (en) * | 1970-06-18 | 1974-03-05 | American Home Prod | Certain 2-substituted-4,6-diamino-5-pyrimidinecarboxaldehydes |
US3725405A (en) * | 1970-06-18 | 1973-04-03 | American Home Prod | 2,4,7-TRISUBSTITUTED-{8 PYRIDO 2,3-d{9 PYRIMIDINE-6-CARBOXAMIDES |
US3707475A (en) | 1970-11-16 | 1972-12-26 | Pfizer | Antiinflammatory imidazoles |
US3929807A (en) | 1971-05-10 | 1975-12-30 | Ciba Geigy Corp | 2-Substituted-4(5)-(aryl)-5(4)-(2,3 or -4-pyridyl)-imidazoles |
US3940486A (en) | 1971-05-10 | 1976-02-24 | Ciba-Geigy Corporation | Imidazole derivatives in the treatment of pain |
CA966134A (en) * | 1972-05-05 | 1975-04-15 | Haydn W.R. Williams | 1,8-naphthyridine compounds |
US4058614A (en) | 1973-12-04 | 1977-11-15 | Merck & Co., Inc. | Substituted imidazole compounds and therapeutic compositions therewith |
US4199592A (en) | 1978-08-29 | 1980-04-22 | E. I. Du Pont De Nemours And Company | Antiinflammatory 4,5-diaryl-2-nitroimidazoles |
JPS5618982A (en) * | 1979-06-14 | 1981-02-23 | Wellcome Found | Pyrimidine derivatives and medicinal drug containing them |
DD201677A5 (de) | 1980-07-25 | 1983-08-03 | Ciba Geigy | Verfahren zur herstellung von trisubstituierten imidazolderivaten |
GB2123831B (en) | 1981-07-20 | 1986-01-15 | Ciba Geigy Ag | Trisubstituted oxazo compounds |
US4503065A (en) | 1982-08-03 | 1985-03-05 | E. I. Du Pont De Nemours And Company | Antiinflammatory 4,5-diaryl 1-2-halo imidazoles |
JPS60226882A (ja) | 1984-04-24 | 1985-11-12 | Nippon Zoki Pharmaceut Co Ltd | 新規ピリミドピリミジン誘導体 |
US4565875A (en) | 1984-06-27 | 1986-01-21 | Fmc Corporation | Imidazole plant growth regulators |
US4560691A (en) * | 1984-07-13 | 1985-12-24 | Sterling Drug Inc. | 5-(Phenyl)-1,6-naphthyridin-2(1H)-ones, their cardiotonic use and preparation |
US4686231A (en) | 1985-12-12 | 1987-08-11 | Smithkline Beckman Corporation | Inhibition of 5-lipoxygenase products |
IL83467A0 (en) | 1986-08-15 | 1988-01-31 | Fujisawa Pharmaceutical Co | Imidazole derivatives,processes for their preparation and pharmaceutical compositions containing the same |
EP0278686A1 (en) | 1987-02-07 | 1988-08-17 | The Wellcome Foundation Limited | Pyridopyrimidines methods for their preparation and pharmaceutical formulations thereof |
JPH01261306A (ja) * | 1988-04-13 | 1989-10-18 | Nippon Kayaku Co Ltd | 2−アルキルチオ−4−アミノピリミジン誘導体を有効成分とする開花促進剤 |
BG94957A (bg) | 1990-08-10 | 1993-12-24 | Ciba - Geigy Ag | Пиримидинови производни и средство за борба срещу вредители по растенията |
FR2665898B1 (fr) | 1990-08-20 | 1994-03-11 | Sanofi | Derives d'amido-3 pyrazole, procede pour leur preparation et compositions pharmaceutiques les contenant. |
IE913473A1 (en) | 1990-10-15 | 1992-04-22 | Fujisawa Pharmaceutical Co | Quinazoline derivatives and their preparation |
JPH06502178A (ja) | 1990-12-31 | 1994-03-10 | 藤沢薬品工業株式会社 | イミダゾトリアジン誘導体 |
JP3375659B2 (ja) | 1991-03-28 | 2003-02-10 | テキサス インスツルメンツ インコーポレイテツド | 静電放電保護回路の形成方法 |
WO1992020642A1 (en) * | 1991-05-10 | 1992-11-26 | Rhone-Poulenc Rorer International (Holdings) Inc. | Bis mono-and bicyclic aryl and heteroaryl compounds which inhibit egf and/or pdgf receptor tyrosine kinase |
FR2676734B1 (fr) | 1991-05-23 | 1995-05-19 | Roussel Uclaf | Nouveaux derives de la pyrimidine, leur procede de preparation, les nouveaux intermediaires obtenus, leur application a titre de medicaments et les compositions pharmaceutiques les renfermant. |
IL102764A0 (en) | 1991-08-16 | 1993-01-31 | Merck & Co Inc | Quinazoline derivatives,and pharmaceutical compositions containing them |
DE4131029A1 (de) * | 1991-09-18 | 1993-07-29 | Basf Ag | Substituierte pyrido (2,3-d) pyrimidine als antidots |
US5656644A (en) | 1994-07-20 | 1997-08-12 | Smithkline Beecham Corporation | Pyridyl imidazoles |
US5916891A (en) | 1992-01-13 | 1999-06-29 | Smithkline Beecham Corporation | Pyrimidinyl imidazoles |
IL104369A0 (en) | 1992-01-13 | 1993-05-13 | Smithkline Beecham Corp | Novel compounds and compositions |
US6008235A (en) | 1992-01-13 | 1999-12-28 | Smithkline Beecham Corporation | Pyridyl substituted imidazoles |
US5716972A (en) | 1993-01-13 | 1998-02-10 | Smithkline Beecham Corporation | Pyridyl substituted imidazoles |
GB9303993D0 (en) | 1993-02-26 | 1993-04-14 | Fujisawa Pharmaceutical Co | New heterocyclic derivatives |
US5466692A (en) * | 1993-03-24 | 1995-11-14 | American Home Products Corporation | Substituted pyridopyrimidines and antihypertensives |
US5593992A (en) | 1993-07-16 | 1997-01-14 | Smithkline Beecham Corporation | Compounds |
US5670527A (en) | 1993-07-16 | 1997-09-23 | Smithkline Beecham Corporation | Pyridyl imidazole compounds and compositions |
US5593991A (en) | 1993-07-16 | 1997-01-14 | Adams; Jerry L. | Imidazole compounds, use and process of making |
US5869043A (en) | 1993-09-17 | 1999-02-09 | Smithkline Beecham Corporation | Drug binding protein |
US5871934A (en) | 1993-09-17 | 1999-02-16 | Smithkline Beecham Corporation | Screening methods using cytokine suppressive anti-inflammatory drug (CSAID) binding proteins |
US5783664A (en) | 1993-09-17 | 1998-07-21 | Smithkline Beecham Corporation | Cytokine suppressive anit-inflammatory drug binding proteins |
US5426110A (en) * | 1993-10-06 | 1995-06-20 | Eli Lilly And Company | Pyrimidinyl-glutamic acid derivatives |
EP0727998B1 (en) | 1993-11-08 | 2004-01-21 | Smithkline Beecham Corporation | Oxazoles for treating cytokine mediated diseases |
GB9325217D0 (en) | 1993-12-09 | 1994-02-09 | Zeneca Ltd | Pyrimidine derivatives |
IL112249A (en) | 1994-01-25 | 2001-11-25 | Warner Lambert Co | Pharmaceutical compositions containing di and tricyclic pyrimidine derivatives for inhibiting tyrosine kinases of the epidermal growth factor receptor family and some new such compounds |
US5559137A (en) | 1994-05-16 | 1996-09-24 | Smithkline Beecham Corp. | Compounds |
US5547954A (en) | 1994-05-26 | 1996-08-20 | Fmc Corporation | 2,4-Diamino-5,6-disubstituted-and 5,6,7-trisubstituted-5-deazapteridines as insecticides |
US5545669A (en) | 1994-06-02 | 1996-08-13 | Adams; Jerry L. | Anti-inflammatory compounds |
TW574214B (en) | 1994-06-08 | 2004-02-01 | Pfizer | Corticotropin releasing factor antagonists |
MX9701600A (es) * | 1994-08-29 | 1997-05-31 | Yamanouchi Pharma Co Ltd | Derivados de naftiridina novedosos y composicion medicinal de los mismos. |
IL115256A0 (en) * | 1994-11-14 | 1995-12-31 | Warner Lambert Co | 6-Aryl pyrido (2,3-d) pyrimidines and naphthyridines and their use |
US5620981A (en) * | 1995-05-03 | 1997-04-15 | Warner-Lambert Company | Pyrido [2,3-D]pyrimidines for inhibiting protein tyrosine kinase mediated cellular proliferation |
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 |
IL118544A (en) | 1995-06-07 | 2001-08-08 | Smithkline Beecham Corp | History of imidazole, the process for their preparation and the pharmaceutical preparations containing them |
ATE240325T1 (de) | 1995-06-07 | 2003-05-15 | Wyeth Corp | Verfahren zur herstellung von biphenylderivaten |
US5739143A (en) | 1995-06-07 | 1998-04-14 | Smithkline Beecham Corporation | Imidazole compounds and compositions |
US5760220A (en) * | 1995-06-07 | 1998-06-02 | American Home Products Corporation | Process for preparation of biphenyl derivatives |
ZA9610687B (en) | 1995-12-22 | 1997-09-29 | Smithkline Beecham Corp | Novel synthesis. |
ZA97175B (en) | 1996-01-11 | 1997-11-04 | Smithkline Beecham Corp | Novel substituted imidazole compounds. |
AU715900B2 (en) | 1996-01-11 | 2000-02-10 | Smithkline Beecham Corporation | Novel substituted imidazole compounds |
US6150337A (en) | 1996-01-23 | 2000-11-21 | Icn Pharmaceuticals, Inc. | Specific modulation of Th1/Th2 cytokine expression by Ribavirin in activated T-lymphocytes |
US5767097A (en) | 1996-01-23 | 1998-06-16 | Icn Pharmaceuticals, Inc. | Specific modulation of Th1/Th2 cytokine expression by ribavirin in activated T-lymphocytes |
US20020137696A1 (en) | 1996-01-23 | 2002-09-26 | Robert Tam | Specific modulation of TH1/TH2 cytokine expression by ribavirin in activated T-lymphocytes |
WO1997032583A1 (en) | 1996-03-08 | 1997-09-12 | Smithkline Beecham Corporation | Use of csaidtm compounds as inhibitors of angiogenesis |
WO1997033883A1 (en) | 1996-03-13 | 1997-09-18 | Smithkline Beecham Corporation | Novel pyrimidine compounds useful in treating cytokine mediated diseases |
US6235760B1 (en) | 1996-03-25 | 2001-05-22 | Smithkline Beecham Corporation | Treatment for CNS injuries |
US6096739A (en) | 1996-03-25 | 2000-08-01 | Smithkline Beecham Corporation | Treatment for CNS injuries |
AU2521597A (en) | 1996-04-12 | 1997-11-07 | Sumitomo Pharmaceuticals Company, Limited | Piperidinylpyramidine derivatives |
US6875769B2 (en) * | 1996-05-23 | 2005-04-05 | Pfizer Inc. | Substituted6,6-hetero-bicyclicderivatives |
ZA973884B (en) | 1996-05-23 | 1998-11-06 | Du Pont Merck Pharma | Tetrahydropteridines and pyridylpiperazines for treatment of neurological disorders |
BR9710808A (pt) * | 1996-08-06 | 1999-08-17 | Pfizer | Derivados biciclicos 6,6 ou 6,7 contendo pirito ou pirimido substitu¡dos |
TW477787B (en) | 1996-08-27 | 2002-03-01 | Pfizer | Pyrido six-membered nitrogen-containing cyclic ring derivatives having corticotropin releasing factor antagonist activity and pharmaceutical composition containing same |
US6455690B1 (en) | 1996-10-16 | 2002-09-24 | Robert Tam | L-8-oxo-7-propyl-7,8-dihydro-(9H)-guanosine |
CZ126799A3 (cs) | 1996-10-16 | 1999-07-14 | Icn Pharmaceuticals | Purinové L-nukleosidy a jejich analogy a farmaceutické prostředky, které je obsahují |
US6509320B1 (en) | 1996-10-16 | 2003-01-21 | Icn Pharmaceuticals, Inc. | Purine L-nucleosides, analogs and uses thereof |
WO1998023613A1 (en) | 1996-11-27 | 1998-06-04 | Pfizer Inc. | Fused bicyclic pyrimidine derivatives |
US6147080A (en) | 1996-12-18 | 2000-11-14 | Vertex Pharmaceuticals Incorporated | Inhibitors of p38 |
US5929076A (en) | 1997-01-10 | 1999-07-27 | Smithkline Beecham Corporation | Cycloalkyl substituted imidazoles |
US6268310B1 (en) | 1997-01-28 | 2001-07-31 | Nippon Soda Co., Ltd. | Oxazole derivative, process for producing the same, and herbicide |
WO1998033798A2 (en) | 1997-02-05 | 1998-08-06 | Warner Lambert Company | Pyrido[2,3-d]pyrimidines and 4-amino-pyrimidines as inhibitors of cell proliferation |
US6498163B1 (en) * | 1997-02-05 | 2002-12-24 | Warner-Lambert Company | Pyrido[2,3-D]pyrimidines and 4-aminopyrimidines as inhibitors of cellular proliferation |
US5945422A (en) * | 1997-02-05 | 1999-08-31 | Warner-Lambert Company | N-oxides of amino containing pyrido 2,3-D! pyrimidines |
EP1041989A4 (en) | 1997-10-08 | 2002-11-20 | Smithkline Beecham Corp | NEW SUBSTITUTED CYCLOALCENYL COMPOUNDS |
AR017219A1 (es) | 1997-12-19 | 2001-08-22 | Smithkline Beecham Corp | Derivados de imidazol 1,4,5 sustituidos, composiciones que los comprenden, procedimiento para la preparacion de dichos derivados, uso de los derivados parala manufactura de un medicamento |
US6423695B1 (en) | 1998-01-13 | 2002-07-23 | Ribapharm, Inc. | Cytokine related treatments of disease |
EA200000840A1 (ru) | 1998-02-17 | 2001-02-26 | Туларик, Инк. | Антивирусные производные пиримидина |
US6306866B1 (en) | 1998-03-06 | 2001-10-23 | American Cyanamid Company | Use of aryl-substituted pyrimidines as insecticidal and acaricidal agents |
JP2000038350A (ja) | 1998-05-18 | 2000-02-08 | Yoshitomi Pharmaceut Ind Ltd | 糖尿病治療薬 |
US6248225B1 (en) * | 1998-05-26 | 2001-06-19 | Ppg Industries Ohio, Inc. | Process for forming a two-coat electrodeposited composite coating the composite coating and chip resistant electrodeposited coating composition |
BR9911590A (pt) | 1998-05-26 | 2001-02-13 | Warner Lambert Co | Pirimidinas bicìclicas e 3,4-diidropirimidinas bicìclicas como inibidores da proliferação celular |
US20040044012A1 (en) | 1998-05-26 | 2004-03-04 | Dobrusin Ellen Myra | Bicyclic pyrimidines and bicyclic 3,4-dihydropyrimidines as inhibitors of cellular proliferation |
US6423425B1 (en) | 1998-05-26 | 2002-07-23 | Ppg Industries Ohio, Inc. | Article having a chip-resistant electrodeposited coating and a process for forming an electrodeposited coating |
JP2002517486A (ja) | 1998-06-12 | 2002-06-18 | バーテックス ファーマシューティカルズ インコーポレイテッド | p38のインヒビター |
US6184226B1 (en) | 1998-08-28 | 2001-02-06 | Scios Inc. | Quinazoline derivatives as inhibitors of P-38 α |
JP2002526482A (ja) | 1998-09-18 | 2002-08-20 | バーテックス ファーマシューティカルズ インコーポレイテッド | p38のインヒビター |
EP1117653B1 (en) | 1998-10-01 | 2003-02-05 | AstraZeneca AB | Quinoline and quinazoline derivatives and their use as inhibitors of cytokine mediated diseases |
WO2000023444A1 (en) | 1998-10-21 | 2000-04-27 | Abbott Laboratories | 5,7-disubstituted-4-aminopyrido[2,3-d]pyrimidine compounds |
CZ20011394A3 (cs) | 1998-10-23 | 2001-12-12 | F. Hoffmann-La Roche Ag | Derivát bicyklických, dusík obsahujících heterocyklických sloučenin, způsob jeho přípravy a farmaceutický prostředek, který ho obsahuje |
US6358959B1 (en) | 1999-01-26 | 2002-03-19 | Merck & Co., Inc. | Polyazanaphthalenone derivatives useful as alpha 1a adrenoceptor antagonists |
EP1040831A3 (en) | 1999-04-02 | 2003-05-02 | Pfizer Products Inc. | Use of corticotropin releasing factor (CRF) antagonists to prevent sudden death |
DE60027431T2 (de) | 1999-07-02 | 2007-07-12 | Stuart A. Rancho Santa Fe Lipton | Verwendung von p38 MAPK Inhibitoren in der Behandlung von Augenkrankheiten |
KR20020032591A (ko) | 1999-09-17 | 2002-05-03 | 스튜어트 알. 수터, 스티븐 베네티아너, 피터 존 기딩스 | 라이노바이러스 감염에서의 csaid의 용도 |
CZ2002934A3 (cs) | 1999-09-17 | 2002-07-17 | Abbott Gmbh & Co. Kg | Inhibitory kinázy jako terapeutická činidla |
AU2576501A (en) | 1999-12-08 | 2001-06-18 | Advanced Medicine, Inc. | Protein kinase inhibitors |
ES2433476T3 (es) | 2000-01-21 | 2013-12-11 | Novartis Ag | Combinaciones que contienen inhibidores de la dipeptidilpeptidasa-IV y agentes 5 antidiabéticos |
PE20011066A1 (es) | 2000-01-25 | 2001-10-22 | Warner Lambert Co | PIRIDO [2,3-d] PIRIMIDIN-2,7-DIAMINAS INHIBIDORES DE CINASAS |
SK10772002A3 (sk) * | 2000-01-27 | 2004-01-08 | Warner-Lambert Company | Pyridopyrimidinónové deriváty na liečbu neurodegeneratívnych ochorení |
AR030053A1 (es) * | 2000-03-02 | 2003-08-13 | Smithkline Beecham Corp | 1h-pirimido [4,5-d] pirimidin-2-onas y sales, composiciones farmaceuticas, uso para la fabricacion de un medicamento y procedimiento para producirlas |
US7235551B2 (en) | 2000-03-02 | 2007-06-26 | Smithkline Beecham Corporation | 1,5-disubstituted-3,4-dihydro-1h-pyrimido[4,5-d]pyrimidin-2-one compounds and their use in treating csbp/p38 kinase mediated diseases |
AP2002002643A0 (en) | 2000-03-06 | 2002-12-31 | Warner Lambert Co | 5-alkylpyrido[2,3-d]pyrimidines tyrosine kinase inhibitors |
AU2002248269A1 (en) | 2000-10-19 | 2002-08-12 | Smithkline Beecham Corporation | Use of p38 inhibitors for the treatment of inflammation-enhanced cough |
EP1333833B1 (en) | 2000-10-23 | 2011-08-24 | GlaxoSmithKline LLC | Novel trisubstituted-8H-pyrido[2,3-d]pyrimidin-7-one compound for the treatment of CSBP/p38 kinase mediated diseases |
JP2002205986A (ja) | 2000-11-08 | 2002-07-23 | Takeda Chem Ind Ltd | ピリミジン誘導体およびそれを含有する除草剤 |
WO2002058695A1 (en) | 2000-12-20 | 2002-08-01 | Merck & Co., Inc. | (halo-benzo carbonyl)heterocyclo fused phenyl p38 kinase inhibiting agents |
AU2002258400A1 (en) | 2001-02-16 | 2002-08-28 | Tularik Inc. | Methods of using pyrimidine-based antiviral agents |
DE10108481A1 (de) | 2001-02-22 | 2002-10-24 | Bayer Ag | Pyridylpyrimidine |
WO2002088079A2 (en) | 2001-05-01 | 2002-11-07 | Bristol-Myers Squibb Company | Dual inhibitors of pde 7 and pde 4 |
US7105667B2 (en) | 2001-05-01 | 2006-09-12 | Bristol-Myers Squibb Co. | Fused heterocyclic compounds and use thereof |
PE20030008A1 (es) | 2001-06-19 | 2003-01-22 | Bristol Myers Squibb Co | Inhibidores duales de pde 7 y pde 4 |
WO2002102313A2 (en) | 2001-06-19 | 2002-12-27 | Bristol-Myers Squibb Company | Pyrimidine inhibitors of phosphodiesterase (pde) 7 |
GB0124941D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
JP4178783B2 (ja) | 2001-10-19 | 2008-11-12 | 三菱化学株式会社 | 光学記録媒体 |
US7019002B2 (en) * | 2001-12-11 | 2006-03-28 | Pharmacia & Upjohn, S.P.A. | Pyridopyrimidinones derivatives as telomerase inhibitors |
KR20050006221A (ko) * | 2002-05-06 | 2005-01-15 | 제네랩스 테크놀로지스, 인코포레이티드 | C형 간염 바이러스 감염 치료용의 뉴클레오시드 유도체 |
ITBO20020304A1 (it) | 2002-05-17 | 2003-11-17 | Magneti Marelli Powertrain Spa | Nuovi condotti in materiale polimerico |
TW200413381A (en) | 2002-11-04 | 2004-08-01 | Hoffmann La Roche | Novel amino-substituted dihydropyrimido [4,5-d]pyrimidinone derivatives, their manufacture and use as pharmaceutical agents |
US7384937B2 (en) * | 2002-11-06 | 2008-06-10 | Bristol-Myers Squibb Co. | Fused heterocyclic compounds and use thereof |
JP2004203751A (ja) | 2002-12-24 | 2004-07-22 | Pfizer Inc | 置換6,6−ヘテロ二環式誘導体 |
EP1590341B1 (en) * | 2003-01-17 | 2009-06-17 | Warner-Lambert Company LLC | 2-aminopyridine substituted heterocycles as inhibitors of cellular proliferation |
US7138412B2 (en) * | 2003-03-11 | 2006-11-21 | Bristol-Myers Squibb Company | Tetrahydroquinoline derivatives useful as serine protease inhibitors |
EP1636195A1 (en) * | 2003-05-27 | 2006-03-22 | Pfizer Products Inc. | Quinazolines and pyrido[3,4-d]pyrimidines as receptor tyrosine kinase inhibitors |
TW200521119A (en) * | 2003-08-05 | 2005-07-01 | Vertex Pharma | Compositions useful as inhibitors of voltage-gated ion channels |
DE102004020908A1 (de) | 2004-04-28 | 2005-11-17 | Grünenthal GmbH | Substituierte 5,6,7,8,-Tetrahydro-pyrido[4,3-d]pyrimidin-2-yl- und 5,6,7,8,-Tetrahydro-chinazolin-2-yl-Verbindungen |
US7098222B2 (en) * | 2004-05-12 | 2006-08-29 | Abbott Laboratories | Bicyclic-substituted amines having cyclic-substituted monocyclic substituents |
AR053346A1 (es) | 2005-03-25 | 2007-05-02 | Glaxo Group Ltd | Compuesto derivado de 8h -pirido (2,3-d) pirimidin -7 ona 2,4,8- trisustituida composicion farmaceutica y uso para preparar una composicion para tratamiento y profilxis de una enfermedad mediada por la quinasa csbp/ rk/p38 |
JP2008535822A (ja) | 2005-03-25 | 2008-09-04 | グラクソ グループ リミテッド | 新規化合物 |
CN101495475A (zh) | 2005-03-25 | 2009-07-29 | 葛兰素集团有限公司 | 制备吡啶并[2,3-d]嘧啶-7-酮和3,4-二氢嘧啶并[4,5-d]嘧啶-2(1H)-酮衍生物的方法 |
TW200724142A (en) | 2005-03-25 | 2007-07-01 | Glaxo Group Ltd | Novel compounds |
WO2006127678A2 (en) | 2005-05-23 | 2006-11-30 | Smithkline Beecham Corporation | Inhibition of p38 mark for treatment of obesity |
EP1931667A1 (en) | 2005-09-28 | 2008-06-18 | Ranbaxy Laboratories Limited | Pyrido-pyridimidine derivatives useful as antiinflammatory agents |
EP1940839B1 (en) | 2005-10-07 | 2013-07-31 | Exelixis, Inc. | PYRIDOPYRIMIDINONE INHIBITORS OF PI3Kalpha |
PE20070823A1 (es) | 2005-11-15 | 2007-08-09 | Glaxo Group Ltd | Sal tosilato de 8-(2,6-difluorofenil)-4-(4-fluoro-2-metilfenil)-2-{[2-hidroxi-1-(hidroximetil)etil]amino}pirido[2,3-]pirimidin-7(8h)-ona |
US20090170834A1 (en) | 2005-12-22 | 2009-07-02 | Prolexys Pharmaceuticals, Inc. | Fused Pyrimidones and Thiopyrimidones, and Uses Thereof |
TW200800997A (en) | 2006-03-22 | 2008-01-01 | Astrazeneca Ab | Chemical compounds |
JP2010510317A (ja) | 2006-11-20 | 2010-04-02 | ブリストル−マイヤーズ スクイブ カンパニー | ジペプチジルペプチダーゼivの阻害剤としての7,8−ジヒドロ−1,6−ナフチリジン−5(6h)−オンおよび関連二環式化合物、および方法 |
WO2009132980A1 (en) | 2008-04-29 | 2009-11-05 | F. Hoffmann-La Roche Ag | Pyrimidinyl pyridone inhibitors of jnk. |
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