NO323373B1 - Acylderivater, farmasoytisk sammensetning omfattende samme, anvendelse av samme for fremstilling av medikament og fremgangsmate for a binde VLA-4 i en biologisk prove. - Google Patents
Acylderivater, farmasoytisk sammensetning omfattende samme, anvendelse av samme for fremstilling av medikament og fremgangsmate for a binde VLA-4 i en biologisk prove. Download PDFInfo
- Publication number
- NO323373B1 NO323373B1 NO20013600A NO20013600A NO323373B1 NO 323373 B1 NO323373 B1 NO 323373B1 NO 20013600 A NO20013600 A NO 20013600A NO 20013600 A NO20013600 A NO 20013600A NO 323373 B1 NO323373 B1 NO 323373B1
- Authority
- NO
- Norway
- Prior art keywords
- phenylalanine
- dimethylcarbamyloxy
- methyl
- butyl ester
- give
- Prior art date
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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- A—HUMAN NECESSITIES
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PCT/US2000/001686 WO2000043372A1 (en) | 1999-01-22 | 2000-01-21 | Acyl derivatives which treat vla-4 related disorders |
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Families Citing this family (83)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL143929A0 (en) * | 1999-01-22 | 2002-04-21 | Elan Pharm Inc | Acyl derivatives which treat vla-4 related disorders |
TW200307671A (en) * | 2002-05-24 | 2003-12-16 | Elan Pharm Inc | Heteroaryl compounds which inhibit leukocyte adhesion mediated by α 4 integrins |
TWI281470B (en) * | 2002-05-24 | 2007-05-21 | Elan Pharm Inc | Heterocyclic compounds which inhibit leukocyte adhesion mediated by alpha4 integrins |
US20050074451A1 (en) * | 2003-06-25 | 2005-04-07 | Elan Pharmaceuticals, Inc. | Methods and compositions for treating rheumatoid arthritis |
US7419666B1 (en) | 2004-02-23 | 2008-09-02 | Massachusetts Eye And Ear Infirmary | Treatment of ocular disorders |
WO2005111020A2 (en) * | 2004-04-30 | 2005-11-24 | Elan Pharmaceuticals, Inc. | Pyrimidine hydantoin analogues which inhibit leukocyte adhesion mediated by vla-4 |
US20050250945A1 (en) * | 2004-05-07 | 2005-11-10 | Xiaobing Li | Triazine compounds as inhibitors of bacterial type III protein secretion systems |
KR101273614B1 (ko) * | 2004-07-08 | 2013-06-12 | 엘란 파마슈티칼스, 인크. | 중합체 부분을 포함하는 다가 vla―4 길항제 |
GB0416699D0 (en) * | 2004-07-27 | 2004-09-01 | Prometic Biosciences Ltd | Prion protein ligands and methods of use |
EP1881982B1 (de) * | 2005-05-20 | 2013-11-20 | Elan Pharmaceuticals Inc. | Imidazolon-phenylalanin-derivate als vla-4-antagonisten |
JP5614930B2 (ja) * | 2005-06-10 | 2014-10-29 | プロメティック バイオサイエンシズ,リミテッド | タンパク質結合性リガンドとしてのトリアジン |
EP1901778A2 (de) * | 2005-07-08 | 2008-03-26 | Elan Pharmaceuticals Inc. | Herstellung von polymerkonjugaten von therapeutischen und landwirtschaftlichen verbindungen sowie lebensmittelzusatzverbindungen |
CA2624524C (en) * | 2005-09-29 | 2014-07-08 | Elan Pharmaceuticals, Inc. | Carbamate compounds which inhibit leukocyte adhesion mediated by vla-4 |
EA015388B1 (ru) * | 2005-09-29 | 2011-08-30 | Элан Фамэсьютикэлс, Инк. | ПИРИМИДИНИЛАМИДНЫЕ СОЕДИНЕНИЯ (ВАРИАНТЫ), ВКЛЮЧАЮЩАЯ ИХ ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И СПОСОБ ЛЕЧЕНИЯ ЗАБОЛЕВАНИЯ, ОПОСРЕДОВАННОГО α4-ИНТЕГРИНАМИ |
NZ570679A (en) * | 2006-02-27 | 2011-01-28 | Elan Pharm Inc | Pyrimidinyl sulfonamide compounds which inhibit leukocyte adhesion mediated By VLA-4 |
GB0612669D0 (en) * | 2006-06-27 | 2006-08-09 | Univ Leeds | Biomarkers for preeclampsia |
US9867530B2 (en) | 2006-08-14 | 2018-01-16 | Volcano Corporation | Telescopic side port catheter device with imaging system and method for accessing side branch occlusions |
AU2008218199B2 (en) * | 2007-02-22 | 2013-10-31 | Genentech, Inc. | Methods for detecting inflammatory bowel disease |
US20080287452A1 (en) * | 2007-05-16 | 2008-11-20 | Wyeth | Heteroaryl/aryl pyrimidine analogs and their use as agonists of the wnt-beta-catenin cellular messaging system |
US10219780B2 (en) | 2007-07-12 | 2019-03-05 | Volcano Corporation | OCT-IVUS catheter for concurrent luminal imaging |
US9596993B2 (en) | 2007-07-12 | 2017-03-21 | Volcano Corporation | Automatic calibration systems and methods of use |
JP5524835B2 (ja) | 2007-07-12 | 2014-06-18 | ヴォルカノ コーポレイション | 生体内撮像用カテーテル |
NZ591366A (en) | 2008-09-11 | 2012-05-25 | Pfizer | Heteroaryls amide derivatives and their use as glucokinase activators |
WO2010084428A1 (en) * | 2009-01-20 | 2010-07-29 | Pfizer Inc. | Substituted pyrazinone amides |
KR101295937B1 (ko) * | 2009-03-11 | 2013-08-14 | 화이자 인코포레이티드 | 글루코카이네이즈 억제제로서 사용되는 벤조푸라닐 유도체 |
CN102459179A (zh) * | 2009-04-27 | 2012-05-16 | 艾伦药物公司 | α-4整联蛋白的吡啶酮拮抗剂 |
EP2467159A1 (de) | 2009-08-20 | 2012-06-27 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Vla-4 als biomarker zur prognose und target zur behandlung der duchenne-muskeldystrophie |
AR081930A1 (es) * | 2010-06-16 | 2012-10-31 | Ardea Biosciences Inc | Compuestos de tioacetato |
CN103347866B (zh) | 2010-11-29 | 2016-05-18 | 加林制药公司 | 作为治疗呼吸控制不适或疾病的呼吸兴奋剂的新化合物 |
US20120295911A1 (en) | 2010-11-29 | 2012-11-22 | Galleon Pharmaceuticals, Inc. | Novel Compounds and Compositions for Treatment of Breathing Control Disorders or Diseases |
US11141063B2 (en) | 2010-12-23 | 2021-10-12 | Philips Image Guided Therapy Corporation | Integrated system architectures and methods of use |
US11040140B2 (en) | 2010-12-31 | 2021-06-22 | Philips Image Guided Therapy Corporation | Deep vein thrombosis therapeutic methods |
US9360630B2 (en) | 2011-08-31 | 2016-06-07 | Volcano Corporation | Optical-electrical rotary joint and methods of use |
WO2013052550A2 (en) | 2011-10-04 | 2013-04-11 | Janus Biotherapeutics, Inc. | Novel imidazole quinoline-based immune system modulators |
US9367965B2 (en) | 2012-10-05 | 2016-06-14 | Volcano Corporation | Systems and methods for generating images of tissue |
US9286673B2 (en) | 2012-10-05 | 2016-03-15 | Volcano Corporation | Systems for correcting distortions in a medical image and methods of use thereof |
US10568586B2 (en) | 2012-10-05 | 2020-02-25 | Volcano Corporation | Systems for indicating parameters in an imaging data set and methods of use |
US9324141B2 (en) | 2012-10-05 | 2016-04-26 | Volcano Corporation | Removal of A-scan streaking artifact |
JP2015532536A (ja) | 2012-10-05 | 2015-11-09 | デイビッド ウェルフォード, | 光を増幅するためのシステムおよび方法 |
US10070827B2 (en) | 2012-10-05 | 2018-09-11 | Volcano Corporation | Automatic image playback |
US9307926B2 (en) | 2012-10-05 | 2016-04-12 | Volcano Corporation | Automatic stent detection |
US11272845B2 (en) | 2012-10-05 | 2022-03-15 | Philips Image Guided Therapy Corporation | System and method for instant and automatic border detection |
US9858668B2 (en) | 2012-10-05 | 2018-01-02 | Volcano Corporation | Guidewire artifact removal in images |
US9292918B2 (en) | 2012-10-05 | 2016-03-22 | Volcano Corporation | Methods and systems for transforming luminal images |
US9840734B2 (en) | 2012-10-22 | 2017-12-12 | Raindance Technologies, Inc. | Methods for analyzing DNA |
EP2931132B1 (de) | 2012-12-13 | 2023-07-05 | Philips Image Guided Therapy Corporation | Vorrichtung zur gezielten kanülierung |
JP6785554B2 (ja) | 2012-12-20 | 2020-11-18 | ボルケーノ コーポレイション | 平滑遷移カテーテル |
US10939826B2 (en) | 2012-12-20 | 2021-03-09 | Philips Image Guided Therapy Corporation | Aspirating and removing biological material |
CA2895989A1 (en) | 2012-12-20 | 2014-07-10 | Nathaniel J. Kemp | Optical coherence tomography system that is reconfigurable between different imaging modes |
US10942022B2 (en) | 2012-12-20 | 2021-03-09 | Philips Image Guided Therapy Corporation | Manual calibration of imaging system |
US11406498B2 (en) | 2012-12-20 | 2022-08-09 | Philips Image Guided Therapy Corporation | Implant delivery system and implants |
EP2934282B1 (de) | 2012-12-20 | 2020-04-29 | Volcano Corporation | Ortung von intravaskulären bildern |
US9612105B2 (en) | 2012-12-21 | 2017-04-04 | Volcano Corporation | Polarization sensitive optical coherence tomography system |
US9383263B2 (en) | 2012-12-21 | 2016-07-05 | Volcano Corporation | Systems and methods for narrowing a wavelength emission of light |
US10058284B2 (en) | 2012-12-21 | 2018-08-28 | Volcano Corporation | Simultaneous imaging, monitoring, and therapy |
JP2016502884A (ja) | 2012-12-21 | 2016-02-01 | ダグラス メイヤー, | 延在カテーテル本体テレスコープを有する回転可能超音波撮像カテーテル |
JP2016508233A (ja) | 2012-12-21 | 2016-03-17 | ナサニエル ジェイ. ケンプ, | 光学スイッチを用いた電力効率のよい光学バッファリング |
CA2895990A1 (en) | 2012-12-21 | 2014-06-26 | Jerome MAI | Ultrasound imaging with variable line density |
EP2934323A4 (de) | 2012-12-21 | 2016-08-17 | Andrew Hancock | System und verfahren zur mehrpfad-verarbeitung von bildsignalen |
US10413317B2 (en) | 2012-12-21 | 2019-09-17 | Volcano Corporation | System and method for catheter steering and operation |
US9486143B2 (en) | 2012-12-21 | 2016-11-08 | Volcano Corporation | Intravascular forward imaging device |
JP2016508757A (ja) | 2012-12-21 | 2016-03-24 | ジェイソン スペンサー, | 医療データのグラフィカル処理のためのシステムおよび方法 |
US9770172B2 (en) | 2013-03-07 | 2017-09-26 | Volcano Corporation | Multimodal segmentation in intravascular images |
US10226597B2 (en) | 2013-03-07 | 2019-03-12 | Volcano Corporation | Guidewire with centering mechanism |
US11154313B2 (en) | 2013-03-12 | 2021-10-26 | The Volcano Corporation | Vibrating guidewire torquer and methods of use |
WO2014164696A1 (en) | 2013-03-12 | 2014-10-09 | Collins Donna | Systems and methods for diagnosing coronary microvascular disease |
WO2014159819A1 (en) | 2013-03-13 | 2014-10-02 | Jinhyoung Park | System and methods for producing an image from a rotational intravascular ultrasound device |
US11026591B2 (en) | 2013-03-13 | 2021-06-08 | Philips Image Guided Therapy Corporation | Intravascular pressure sensor calibration |
US9301687B2 (en) | 2013-03-13 | 2016-04-05 | Volcano Corporation | System and method for OCT depth calibration |
US10292677B2 (en) | 2013-03-14 | 2019-05-21 | Volcano Corporation | Endoluminal filter having enhanced echogenic properties |
US10219887B2 (en) | 2013-03-14 | 2019-03-05 | Volcano Corporation | Filters with echogenic characteristics |
WO2014152365A2 (en) | 2013-03-14 | 2014-09-25 | Volcano Corporation | Filters with echogenic characteristics |
EP3052189A4 (de) * | 2013-10-03 | 2017-11-01 | Leuvas Therapeutics | Modulation der leukozyten-aktivität bei der behandlung neuroinflammatorischer degenerativer erkrankungen |
EP3116862B1 (de) * | 2014-03-10 | 2019-04-17 | Merck Sharp & Dohme Corp. | Piperazinderivate als hiv-proteasehemmer |
EP3551046B1 (de) | 2016-12-07 | 2023-07-19 | Biora Therapeutics, Inc. | Verfahren, vorrichtungen und systeme zur detektion des magen-darm-trakts |
TW201834710A (zh) | 2016-12-14 | 2018-10-01 | 美商寶珍那提公司 | 以整合素抑制劑治療胃腸道疾病 |
AU2017388466B2 (en) | 2016-12-29 | 2022-04-28 | Minoryx Therapeutics S.L. | Heteroaryl compounds and their use |
EP3810085A1 (de) | 2018-06-20 | 2021-04-28 | Progenity, Inc. | Behandlung der erkrankung des gastrointestinaltraktes mit einem integrin-inhibitor |
WO2019245910A1 (en) * | 2018-06-22 | 2019-12-26 | Aduro Biotech, Inc. | Triazine compounds and uses thereof |
KR20210095165A (ko) | 2018-11-19 | 2021-07-30 | 프로제너티, 인크. | 바이오의약품으로 질환을 치료하기 위한 방법 및 디바이스 |
CN110208413B (zh) * | 2019-06-18 | 2021-09-28 | 中国药科大学 | 血清生物标志物在制备issu的诊断试剂中的应用 |
CN115666704A (zh) | 2019-12-13 | 2023-01-31 | 比奥拉治疗股份有限公司 | 用于将治疗剂递送至胃肠道的可摄取装置 |
WO2022162164A1 (en) | 2021-01-29 | 2022-08-04 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods of assessing the risk of developing progressive multifocal leukoencephalopathy in patients treated with vla-4 antagonists |
Family Cites Families (94)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US577A (en) * | 1838-01-20 | Uvtachine for threshing grain and shelling corn | ||
DE2525656A1 (de) | 1974-06-19 | 1976-01-15 | Sandoz Ag | Verfahren zur herstellung neuer heterocyclischer verbindungen |
US4104392A (en) | 1974-11-08 | 1978-08-01 | Mitsubishi Chemical Industries Ltd. | N2 -naphthalenesulfonyl-L-argininamides and the pharmaceutically acceptable salts thereof, and antithrombotic compositions and methods employing them |
US4041156A (en) | 1974-11-08 | 1977-08-09 | Mitsubishi Chemical Industries Limited | N2 -alkoxynaphthalenesulfonyl-L-argininamides and the pharmaceutically acceptable salts thereof |
US4018915A (en) | 1976-01-05 | 1977-04-19 | Mitsubishi Chemical Industries Ltd. | N2 -alkoxynaphthalenesulfonyl-L-argininamides and the pharmaceutically acceptable salts thereof |
US4046876A (en) | 1974-11-08 | 1977-09-06 | Mitsubishi Chemical Industries Limited | N2 -alkoxynaphthalenesulfonyl-L-argininamides and the pharmaceutically acceptable salts thereof |
US4055636A (en) | 1974-11-08 | 1977-10-25 | Mitsubishi Chemical Industries Ltd. | N2 -alkoxynaphthalenesulfonyl-L-argininamides and the pharmaceutically acceptable salts thereof |
US4055651A (en) | 1974-11-08 | 1977-10-25 | Mitsubishi Chemical Industries Ltd. | N2 -alkoxynaphthalenesulfonyl-L-argininamides and the pharmaceutically acceptable salts thereof |
US4096255A (en) | 1974-11-08 | 1978-06-20 | Mitsubishi Chemical Industries Limited | N2 -naphthalenesulfonyl-L-argininamides, and pharmaceutical salts, compositions and methods |
US4073914A (en) | 1974-11-08 | 1978-02-14 | Mitsubishi Chemical Industries Limited | N2 -naphthalenesulfonyl-L-argininamides and the pharmaceutically acceptable salts thereof |
US4070457A (en) | 1974-11-08 | 1978-01-24 | Mitsubishi Chemical Industries Ltd. | N2 -naphthalenesulfonyl-L-argininamides and the pharmaceutically acceptable salts thereof |
JPS5727454B2 (de) | 1975-02-21 | 1982-06-10 | ||
US4036955A (en) | 1976-07-22 | 1977-07-19 | Mitsubishi Chemical Industries Ltd. | N2 -naphthalenesulfonyl-L-argininamides and the pharmaceutically acceptable salts thereof |
US4018913A (en) | 1976-01-14 | 1977-04-19 | Mitsubishi Chemical Industries Ltd. | N2 -alkoxynaphthalenesulfonyl-L-argininamides and the pharmaceutically acceptable salts thereof |
CA1102316A (en) | 1975-12-09 | 1981-06-02 | Shosuke Okamoto | N su2 xx-arylsulfonyl-l-argininamides and the pharmaceutically acceptable salts thereof |
US4101392A (en) * | 1976-12-22 | 1978-07-18 | Monsanto Company | Process for electrolytic oxidative methyl-methyl coupling of cresol salts |
DE2742173A1 (de) | 1977-09-20 | 1979-03-29 | Bayer Ag | Phenoxy-pyridinyl(pyrimidinyl)-alkanole, verfahren zu ihrer herstellung sowie ihre verwendung als fungizide |
US4235871A (en) * | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
IT1211096B (it) | 1981-08-20 | 1989-09-29 | Lpb Ist Farm | Pirimidine e s.triazinici adattivita' ipolipidemizzante. |
US4672065A (en) | 1982-11-19 | 1987-06-09 | Chevron Research Company | N-substituted phenoxyacetamide fungicides |
US4501728A (en) * | 1983-01-06 | 1985-02-26 | Technology Unlimited, Inc. | Masking of liposomes from RES recognition |
CA1218655A (en) * | 1983-01-28 | 1987-03-03 | Kathleen Biziere | Process for the preparation of pyridazine derivatives having a psychotropic action |
JPS59212480A (ja) * | 1983-05-17 | 1984-12-01 | Nippon Soda Co Ltd | ピリダジン誘導体及び除草剤 |
DE3322720A1 (de) | 1983-06-24 | 1985-01-03 | Chemische Werke Hüls AG, 4370 Marl | Verwendung von in 2-stellung mit (substituierten) aminogruppen substituierten 4-dl-alkylester-(alpha)-alaninyl-6-chlor-s-triazinen als herbizide, insbesondere gegen flughafer |
US4505910A (en) | 1983-06-30 | 1985-03-19 | American Home Products Corporation | Amino-pyrimidine derivatives, compositions and use |
NZ210669A (en) | 1983-12-27 | 1988-05-30 | Syntex Inc | Benzoxazin-4-one derivatives and pharmaceutical compositions |
PH22520A (en) | 1984-11-12 | 1988-10-17 | Yamanouchi Pharma Co Ltd | Heterocyclic compounds having 4-lover alkyl-3-hydroxy-2-lower alkyl phenoxy-lower alkylene-y-group, and process of producing them |
US4959364A (en) | 1985-02-04 | 1990-09-25 | G. D. Searle & Co. | Method of treating inflammation, allergy, asthma and proliferative skin disease using heterocyclic amides |
US5023252A (en) * | 1985-12-04 | 1991-06-11 | Conrex Pharmaceutical Corporation | Transdermal and trans-membrane delivery of drugs |
US4837028A (en) * | 1986-12-24 | 1989-06-06 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
JPH0784424B2 (ja) | 1987-04-15 | 1995-09-13 | 味の素株式会社 | チロシン誘導体及びその用途 |
US4818915A (en) * | 1987-10-22 | 1989-04-04 | Gte Products Corporation | Arc discharge lamp with ultraviolet radiation starting source |
EP0330506A3 (de) | 1988-02-26 | 1990-06-20 | Dana Farber Cancer Institute | VLA-Proteine |
US5011472A (en) * | 1988-09-06 | 1991-04-30 | Brown University Research Foundation | Implantable delivery system for biological factors |
DE3904931A1 (de) | 1989-02-17 | 1990-08-23 | Bayer Ag | Pyridyl-substituierte acrylsaeureester |
US5030644A (en) | 1989-07-31 | 1991-07-09 | Merck & Co., Inc. | Imidazole compounds and their use as transglutaminase inhibitors |
US5260210A (en) | 1989-09-27 | 1993-11-09 | Rubin Lee L | Blood-brain barrier model |
US4992439A (en) | 1990-02-13 | 1991-02-12 | Bristol-Myers Squibb Company | Pyridazine carboxylic acids and esters |
FR2679903B1 (fr) | 1991-08-02 | 1993-12-03 | Elf Sanofi | Derives de la n-sulfonyl indoline portant une fonction amidique, leur preparation, les compositions pharmaceutiques en contenant. |
NZ239846A (en) | 1990-09-27 | 1994-11-25 | Merck & Co Inc | Sulphonamide derivatives and pharmaceutical compositions thereof |
BR9107042A (pt) * | 1990-11-19 | 1993-08-31 | Du Pont | Aminoprimidinas inseticidas,acarcidas e fungicidas |
DE4108029A1 (de) | 1991-03-13 | 1992-09-17 | Bayer Ag | Triazinyl-substituierte acrylsaeureester |
WO1992016549A1 (de) | 1991-03-18 | 1992-10-01 | Pentapharm Ag | Para-substituierte phenylalanin-derivate |
IT1247509B (it) | 1991-04-19 | 1994-12-17 | Univ Cagliari | Composti di sintesi atti all'impiego nella terapia delle infezioni da rhinovirus |
US5296486A (en) | 1991-09-24 | 1994-03-22 | Boehringer Ingelheim Pharmaceuticals, Inc. | Leukotriene biosynthesis inhibitors |
DE4132668C2 (de) | 1991-10-01 | 1993-09-30 | Kammann Maschf Werner | Vorrichtung und Verfahren zum Dekorieren eines kegelförmigen Körpers |
AU3420693A (en) | 1991-12-24 | 1993-07-28 | Fred Hutchinson Cancer Research Center | Competitive inhibition of high-avidity alpha4-beta1 receptor using tripeptide ldv |
CA2130754C (en) | 1992-03-11 | 2005-02-08 | Damian W. Grobelny | Amine derivatives of oxo- and hydroxy-substituted hydrocarbons |
US5518730A (en) | 1992-06-03 | 1996-05-21 | Fuisz Technologies Ltd. | Biodegradable controlled release flash flow melt-spun delivery system |
DE4227748A1 (de) | 1992-08-21 | 1994-02-24 | Bayer Ag | Pyridyloxy-acrylsäureester |
JP2848232B2 (ja) | 1993-02-19 | 1999-01-20 | 武田薬品工業株式会社 | アルデヒド誘導体 |
US5770573A (en) | 1993-12-06 | 1998-06-23 | Cytel Corporation | CS-1 peptidomimetics, compositions and methods of using the same |
TW574214B (en) | 1994-06-08 | 2004-02-01 | Pfizer | Corticotropin releasing factor antagonists |
US5510332A (en) | 1994-07-07 | 1996-04-23 | Texas Biotechnology Corporation | Process to inhibit binding of the integrin α4 62 1 to VCAM-1 or fibronectin and linear peptides therefor |
ATE237342T1 (de) | 1994-07-11 | 2003-05-15 | Athena Neurosciences Inc | Inhibitoren der leukozytenadhäsion |
US6306840B1 (en) | 1995-01-23 | 2001-10-23 | Biogen, Inc. | Cell adhesion inhibitors |
IL117659A (en) | 1995-04-13 | 2000-12-06 | Dainippon Pharmaceutical Co | Substituted 2-phenyl pyrimidino amino acetamide derivative process for preparing the same and a pharmaceutical composition containing same |
DE69611773T2 (de) | 1995-09-29 | 2001-09-13 | Sankyo Co., Ltd. | 13-Substituierte Milbemycin 5-Oxim Derivate, ihre Herstellung und Verwendung gegen Insekten und andere Schädlinge |
DE19536891A1 (de) * | 1995-10-04 | 1997-04-10 | Basf Ag | Neue Aminosäurederivate, ihre Herstellung und Verwendung |
DE19548709A1 (de) * | 1995-12-23 | 1997-07-03 | Merck Patent Gmbh | Tyrosinderivate |
EP0910575B1 (de) | 1996-06-21 | 2002-09-25 | Takeda Chemical Industries, Ltd. | Verfahren zur herstellung von peptiden |
KR20000022190A (ko) | 1996-06-28 | 2000-04-25 | 플레믹 크리스티안 | 인테그린 저해제로서의 페닐알라닌 유도체 |
DE19654483A1 (de) | 1996-06-28 | 1998-01-02 | Merck Patent Gmbh | Phenylalanin-Derivate |
DE19629817A1 (de) | 1996-07-24 | 1998-01-29 | Hoechst Ag | Neue Imino-Derivate als Inhibitoren der Knochenresorption und Vitronectinrezeptor-Antagonisten |
DE19647317A1 (de) | 1996-11-15 | 1998-05-20 | Hoechst Schering Agrevo Gmbh | Substituierte Stickstoff-Heterocyclen, Verfahren zu ihrer Herstellung und ihre Verwendung als Schädlingsbekämpfungsmittel |
HUP0000492A3 (en) | 1996-11-22 | 2000-06-28 | Lilly Co Eli | N-(aryl/heteroarylacetyl) amino acid esters, pharmaceutical compositions comprising same, and methods for inhibiting beta-amyloid peptide release and/or its synthesis by use of such compounds |
WO1998033783A1 (en) | 1997-02-04 | 1998-08-06 | Versicor, Inc. | Solid phase and combinatorial library syntheses of 3,1-benzoxazine-4-ones |
DE19713000A1 (de) | 1997-03-27 | 1998-10-01 | Merck Patent Gmbh | Adhäsionsrezeptor-Antagonisten |
DE69833654T2 (de) | 1997-05-29 | 2006-12-14 | Merck & Co., Inc. (A New Jersey Corp.) | Biarylalkansäuren in der verwendung als zelladhäsionsinhibitoren |
CA2291778A1 (en) * | 1997-05-29 | 1998-12-03 | Merck & Co., Inc. | Heterocyclic amide compounds as cell adhesion inhibitors |
WO1999006432A1 (en) | 1997-07-31 | 1999-02-11 | Elan Pharmaceuticals, Inc. | Dipeptide and related compounds which inhibit leukocyte adhesion mediated by vla-4 |
WO1999006433A1 (en) | 1997-07-31 | 1999-02-11 | Elan Pharmaceuticals, Inc. | Compounds which inhibit leukocyte adhesion mediated by vla-4 |
JP2001512134A (ja) | 1997-07-31 | 2001-08-21 | エラン・ファーマシューティカルズ・インコーポレーテッド | Vla−4仲介性白血球付着を阻害する置換フェニルアラニン型化合物 |
AR016133A1 (es) | 1997-07-31 | 2001-06-20 | Wyeth Corp | Compuesto de carbamiloxi que inhiben la adhesion de leucocitos mediada por vla-4, compuestos que son prodrogas de dichos compuestos, composicionfarmaceutica, metodo para fijar vla-4 a una muestra biologica, metodo para el tratamiento de una condicion inflamatoria |
CA2301377C (en) | 1997-08-22 | 2009-10-06 | F. Hoffmann-La Roche Ag | N-aroylphenylalanine derivatives |
EP1005446B1 (de) | 1997-08-22 | 2004-02-25 | F. Hoffmann-La Roche Ag | N-aroylphenylalaninderivate |
BR9907733A (pt) | 1998-01-23 | 2000-10-17 | Novartis Ag | Antagonistas vla-4 |
US6329372B1 (en) | 1998-01-27 | 2001-12-11 | Celltech Therapeutics Limited | Phenylalanine derivatives |
US6492492B1 (en) * | 1998-04-03 | 2002-12-10 | University Of Washington | Circularly permuted biotin binding proteins |
KR20010087125A (ko) | 1998-04-16 | 2001-09-15 | 데이비드 비. 맥윌리암스 | 인테그린 수용체에 대한 인테그린의 결합을 억제하는 화합물 |
DE19836560A1 (de) | 1998-08-12 | 2000-02-17 | Siemens Ag | Verfahren und Einrichtung zur Überprüfung der Funktionsfähigkeit einer Vermittlungsstelle |
AR035476A1 (es) * | 1999-01-22 | 2004-06-02 | Elan Pharm Inc | Compuestos heteroarilo y heterociclicos con anillo fusionado, los cuales inhiben la adhesion de leucocitos mediada por vla-4, composiciones farmaceuticas, el uso de las mismas para la manufactura de un medicamento y un metodo para fijar vla-4 en una muestra biologica |
IL143929A0 (en) * | 1999-01-22 | 2002-04-21 | Elan Pharm Inc | Acyl derivatives which treat vla-4 related disorders |
US6436904B1 (en) * | 1999-01-25 | 2002-08-20 | Elan Pharmaceuticals, Inc. | Compounds which inhibit leukocyte adhesion mediated by VLA-4 |
US6544994B2 (en) * | 2000-06-07 | 2003-04-08 | Eprov Ag | Pharmaceutical preparation for treating or preventing cardiovascular or neurological disorders by modulating of the activity of nitric oxide synthase |
US6794506B2 (en) | 2000-07-21 | 2004-09-21 | Elan Pharmaceuticals, Inc. | 3-(heteroaryl) alanine derivatives-inhibitors of leukocyte adhesion mediated by VLA-4 |
WO2002008206A1 (en) | 2000-07-21 | 2002-01-31 | Elan Pharmaceuticals, Inc. | 3-amino-2-(4-aminocarbonyloxy)phenyl-propionic acid derivatives as alpha-4- integrin inhibitors |
TW200307671A (en) * | 2002-05-24 | 2003-12-16 | Elan Pharm Inc | Heteroaryl compounds which inhibit leukocyte adhesion mediated by α 4 integrins |
TWI281470B (en) * | 2002-05-24 | 2007-05-21 | Elan Pharm Inc | Heterocyclic compounds which inhibit leukocyte adhesion mediated by alpha4 integrins |
US7049309B2 (en) * | 2003-10-14 | 2006-05-23 | Bristol-Myers Squibb Company | 3-Thia-4-arylquinolin-2-one potassium channel modulators |
KR101273614B1 (ko) * | 2004-07-08 | 2013-06-12 | 엘란 파마슈티칼스, 인크. | 중합체 부분을 포함하는 다가 vla―4 길항제 |
CA2624524C (en) * | 2005-09-29 | 2014-07-08 | Elan Pharmaceuticals, Inc. | Carbamate compounds which inhibit leukocyte adhesion mediated by vla-4 |
EA015388B1 (ru) * | 2005-09-29 | 2011-08-30 | Элан Фамэсьютикэлс, Инк. | ПИРИМИДИНИЛАМИДНЫЕ СОЕДИНЕНИЯ (ВАРИАНТЫ), ВКЛЮЧАЮЩАЯ ИХ ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И СПОСОБ ЛЕЧЕНИЯ ЗАБОЛЕВАНИЯ, ОПОСРЕДОВАННОГО α4-ИНТЕГРИНАМИ |
NZ570679A (en) * | 2006-02-27 | 2011-01-28 | Elan Pharm Inc | Pyrimidinyl sulfonamide compounds which inhibit leukocyte adhesion mediated By VLA-4 |
-
2000
- 2000-01-21 IL IL14392900A patent/IL143929A0/xx active IP Right Grant
- 2000-01-21 CA CA2359115A patent/CA2359115C/en not_active Expired - Fee Related
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- 2000-01-21 DE DE60036918T patent/DE60036918D1/de not_active Expired - Lifetime
- 2000-01-21 HU HU0201213A patent/HUP0201213A3/hu unknown
- 2000-01-21 JP JP2000594785A patent/JP2002535314A/ja active Pending
- 2000-01-21 AU AU34724/00A patent/AU773538B2/en not_active Ceased
- 2000-01-21 CN CNB008040788A patent/CN1220683C/zh not_active Expired - Fee Related
- 2000-01-21 ES ES00913245T patent/ES2339738T3/es not_active Expired - Lifetime
- 2000-01-21 EP EP00904487A patent/EP1144384B1/de not_active Expired - Lifetime
- 2000-01-21 CZ CZ20012361A patent/CZ20012361A3/cs unknown
- 2000-01-21 EP EP00913245A patent/EP1144388B1/de not_active Expired - Lifetime
- 2000-01-21 CA CA002359113A patent/CA2359113A1/en not_active Abandoned
- 2000-01-21 US US09/489,377 patent/US6492372B1/en not_active Expired - Lifetime
- 2000-01-21 BR BR0007663-5A patent/BR0007663A/pt not_active IP Right Cessation
- 2000-01-21 DE DE60043692T patent/DE60043692D1/de not_active Expired - Lifetime
- 2000-01-21 EA EA200100797A patent/EA006301B1/ru not_active IP Right Cessation
- 2000-01-21 AT AT00913245T patent/ATE455106T1/de not_active IP Right Cessation
- 2000-01-24 TW TW089101088A patent/TWI239954B/zh not_active IP Right Cessation
- 2000-01-24 AR ARP000100286A patent/AR033643A1/es active IP Right Grant
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2001
- 2001-06-21 IL IL143929A patent/IL143929A/en not_active IP Right Cessation
- 2001-07-20 NO NO20013600A patent/NO323373B1/no not_active IP Right Cessation
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2002
- 2002-08-15 US US10/218,366 patent/US6911439B2/en not_active Expired - Fee Related
- 2002-08-15 US US10/218,445 patent/US6903088B2/en not_active Expired - Fee Related
- 2002-08-29 HK HK02106386.7A patent/HK1045157A1/zh unknown
- 2002-09-20 US US10/251,442 patent/US7049306B2/en not_active Expired - Fee Related
- 2002-09-26 HK HK02107038.7A patent/HK1046132B/zh not_active IP Right Cessation
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2003
- 2003-12-29 US US10/748,089 patent/US7005433B2/en not_active Expired - Fee Related
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2005
- 2005-01-10 US US11/033,079 patent/US7378529B2/en not_active Expired - Fee Related
- 2005-06-02 US US11/145,489 patent/US7538215B2/en not_active Expired - Fee Related
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2006
- 2006-10-16 US US11/582,293 patent/US7741328B2/en not_active Expired - Fee Related
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2009
- 2009-12-14 US US12/637,719 patent/US7968547B2/en not_active Expired - Fee Related
- 2009-12-22 US US12/645,154 patent/US7973044B2/en not_active Expired - Fee Related
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2011
- 2011-01-21 JP JP2011011456A patent/JP2011079867A/ja not_active Ceased
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