UA76339C2 - Heterocyclic compounds inhigiting leucocyte adhesion mediated by integrin - Google Patents
Heterocyclic compounds inhigiting leucocyte adhesion mediated by integrin Download PDFInfo
- Publication number
- UA76339C2 UA76339C2 UA20041008397A UA20041008397A UA76339C2 UA 76339 C2 UA76339 C2 UA 76339C2 UA 20041008397 A UA20041008397 A UA 20041008397A UA 20041008397 A UA20041008397 A UA 20041008397A UA 76339 C2 UA76339 C2 UA 76339C2
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- UA
- Ukraine
- Prior art keywords
- phenylalanine
- diethylamino
- pyrimidin
- compound
- ylcarbonyloxy
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Classifications
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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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
- C07D239/50—Three nitrogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
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- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Heart & Thoracic Surgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US38302002P | 2002-05-24 | 2002-05-24 | |
| PCT/US2003/016804 WO2003099809A1 (fr) | 2002-05-24 | 2003-05-27 | Composes heterocycliques inhibiteurs de l'adhesion leucocytaire provoquee par des integrines $g(a)4 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA76339C2 true UA76339C2 (en) | 2006-07-17 |
Family
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| Application Number | Title | Priority Date | Filing Date |
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| UA20041008397A UA76339C2 (en) | 2002-05-24 | 2003-05-27 | Heterocyclic compounds inhigiting leucocyte adhesion mediated by integrin |
Country Status (23)
| Country | Link |
|---|---|
| US (3) | US7026328B2 (fr) |
| EP (1) | EP1507775B1 (fr) |
| JP (1) | JP4469715B2 (fr) |
| KR (1) | KR100978832B1 (fr) |
| CN (1) | CN1314682C (fr) |
| AT (1) | ATE419243T1 (fr) |
| AU (1) | AU2003240823C1 (fr) |
| BR (1) | BR0308881A (fr) |
| CA (1) | CA2481926C (fr) |
| DE (1) | DE60325583D1 (fr) |
| DK (1) | DK1507775T3 (fr) |
| EA (1) | EA008256B1 (fr) |
| EC (1) | ECSP045425A (fr) |
| ES (1) | ES2320436T3 (fr) |
| HK (1) | HK1072608A1 (fr) |
| IL (2) | IL164225A0 (fr) |
| MX (1) | MXPA04010995A (fr) |
| NO (1) | NO329933B1 (fr) |
| NZ (1) | NZ535504A (fr) |
| TW (1) | TWI281470B (fr) |
| UA (1) | UA76339C2 (fr) |
| WO (1) | WO2003099809A1 (fr) |
| ZA (1) | ZA200407590B (fr) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| KR100711840B1 (ko) * | 1999-01-22 | 2007-05-02 | 엘란 파마슈티칼스, 인크. | Ｖｌａ-4 관련 질환 치료용 아실 유도체 |
| TWI281470B (en) * | 2002-05-24 | 2007-05-21 | Elan Pharm Inc | Heterocyclic compounds which inhibit leukocyte adhesion mediated by alpha4 integrins |
| UY28391A1 (es) * | 2003-06-25 | 2004-12-31 | Elan Pharm Inc | Metodos y composiciones para tratar artritis reumatoide |
| WO2005111020A2 (fr) * | 2004-04-30 | 2005-11-24 | Elan Pharmaceuticals, Inc. | Analogues d’hydantoïne de pyrimidine qui empêchent l’adhésion des leucocytes par l’intermédiaire de vla-4 |
| US7794700B2 (en) * | 2004-07-08 | 2010-09-14 | Elan Pharmaceuticals Inc. | Multimeric VLA-4 antagonists comprising polymer moieties |
| WO2006127584A1 (fr) | 2005-05-20 | 2006-11-30 | Elan Pharmaceuticals, Inc. | Derives d'imidazolone phenylalanine utilises comme antagonistes de vla-4 |
| CA2851103A1 (fr) | 2005-09-29 | 2007-04-12 | Elan Pharmaceuticals, Inc. | Composes de pyrimidinyl amide qui inhibent l'adherence leucocytaire a mediation par vla-4 |
| ATE493405T1 (de) * | 2005-09-29 | 2011-01-15 | Elan Pharm Inc | Pyrimidinylamidverbindungen, die die durch vla-4 vermittelte leukozytenadhäsion inhibieren |
| JP5135235B2 (ja) * | 2006-02-27 | 2013-02-06 | エラン ファーマシューティカルズ，インコーポレイテッド | Ｖａｌ−４によって媒介される白血球の接着を阻害するピリミジニルスルホンアミド化合物 |
| EP2007392A4 (fr) | 2006-02-28 | 2010-04-07 | Elan Pharm Inc | Méthodes pour traiter des maladies inflammatoires et auto-immunes avec des composés inhibiteurs alpha-4 |
| JP2009528359A (ja) | 2006-02-28 | 2009-08-06 | エラン ファーマシューティカルズ，インコーポレイテッド | ナタリズマブを用いて炎症性疾患および自己免疫性疾患を治療する方法 |
| US20070231319A1 (en) * | 2006-03-03 | 2007-10-04 | Yednock Theodore A | Methods of treating inflammatory and autoimmune diseases with natalizumab |
| CA2708262A1 (fr) * | 2007-12-07 | 2009-06-18 | Elan Pharmaceuticals, Inc. | Procedes et compositions pour traiter des tumeurs liquides |
| EP2085407A1 (fr) | 2008-02-04 | 2009-08-05 | Sahltech I Göteborg AB | Traitement de purpura thrombopénique idiopathique |
| DK2271634T3 (da) * | 2008-04-29 | 2014-05-05 | Integrative Res Lab Sweden Ab | Modulatorer af dopamin-neurotransmission |
| MX2011011326A (es) * | 2009-04-27 | 2012-02-13 | Elan Pharm Inc | Antagonistas de piridinona de las integrinas alfa-4. |
| RS63744B1 (sr) | 2010-01-11 | 2022-12-30 | Biogen Ma Inc | Test za antitela protiv jc virusa |
| US11287423B2 (en) | 2010-01-11 | 2022-03-29 | Biogen Ma Inc. | Assay for JC virus antibodies |
| HUE043339T2 (hu) | 2011-05-31 | 2019-08-28 | Biogen Ma Inc | Módszer a PML kockázatának megállapítására |
| JP6080521B2 (ja) * | 2012-11-30 | 2017-02-15 | インターナショナル・ビジネス・マシーンズ・コーポレーションＩｎｔｅｒｎａｔｉｏｎａｌ Ｂｕｓｉｎｅｓｓ Ｍａｃｈｉｎｅｓ Ｃｏｒｐｏｒａｔｉｏｎ | 広域分散医療情報ネットワークのデータ管理機構 |
| WO2014193804A1 (fr) | 2013-05-28 | 2014-12-04 | Biogen Idec Ma Inc. | Méthodes d'évaluation de risque de développement d'une lemp |
| JP2019500355A (ja) * | 2015-12-30 | 2019-01-10 | セントルイス ユニバーシティ | 汎インテグリンアンタゴニストとしてのメタ−アザ環式アミノ安息香酸誘導体 |
| PE20211866A1 (es) | 2018-10-30 | 2021-09-21 | Gilead Sciences Inc | Derivados de quinolina como inhibidores de la integrina alfa4beta7 |
| US11174256B2 (en) | 2018-10-30 | 2021-11-16 | Gilead Sciences, Inc. | Imidazopyridine derivatives |
| WO2020092401A1 (fr) | 2018-10-30 | 2020-05-07 | Gilead Sciences, Inc. | COMPOSÉS POUR INHIBITION DE L'INTÉGRINE ALPHA 4β7 |
| EP3873897B1 (fr) | 2018-10-30 | 2024-08-14 | Gilead Sciences, Inc. | Dérivés de n-benzoyl-phénylalanine en tant qu'inhibiteurs d'integrin alpha4béta7 pour le traitement de maladies inflammatoires |
| CN109541237A (zh) * | 2018-12-28 | 2019-03-29 | 吴江近岸蛋白质科技有限公司 | 纤维连接蛋白的生物学活性测定方法 |
| WO2021030438A1 (fr) | 2019-08-14 | 2021-02-18 | Gilead Sciences, Inc. | Composés pour l'inhibition de l'intégrine alpha 4 bêta 7 |
Family Cites Families (80)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2525656A1 (de) | 1974-06-19 | 1976-01-15 | Sandoz Ag | Verfahren zur herstellung neuer heterocyclischer verbindungen |
| US4018915A (en) * | 1976-01-05 | 1977-04-19 | Mitsubishi Chemical Industries Ltd. | N2 -alkoxynaphthalenesulfonyl-L-argininamides and the pharmaceutically acceptable salts thereof |
| 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 |
| US4055636A (en) * | 1974-11-08 | 1977-10-25 | Mitsubishi Chemical Industries Ltd. | N2 -alkoxynaphthalenesulfonyl-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 |
| US4073914A (en) * | 1974-11-08 | 1978-02-14 | Mitsubishi Chemical Industries Limited | N2 -naphthalenesulfonyl-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 |
| US4046876A (en) * | 1974-11-08 | 1977-09-06 | Mitsubishi Chemical Industries Limited | N2 -alkoxynaphthalenesulfonyl-L-argininamides and the pharmaceutically acceptable salts thereof |
| JPS5727454B2 (fr) * | 1975-02-21 | 1982-06-10 | ||
| US4018913A (en) * | 1976-01-14 | 1977-04-19 | Mitsubishi Chemical Industries Ltd. | N2 -alkoxynaphthalenesulfonyl-L-argininamides and the pharmaceutically acceptable salts thereof |
| CA1102316A (fr) | 1975-12-09 | 1981-06-02 | Shosuke Okamoto | Traduction non-disponible |
| US4036955A (en) * | 1976-07-22 | 1977-07-19 | Mitsubishi Chemical Industries Ltd. | N2 -naphthalenesulfonyl-L-argininamides and the pharmaceutically acceptable salts thereof |
| 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 (fr) | 1983-01-28 | 1987-03-03 | Kathleen Biziere | Procede de preparation de derives de pyridazine a action psychotrope |
| 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 |
| US4595364A (en) * | 1984-02-15 | 1986-06-17 | Molten Corp. | Dental prosthesis and process for preparing the same |
| 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 |
| EP0330506A3 (fr) | 1988-02-26 | 1990-06-20 | Dana Farber Cancer Institute | Protéines VLA |
| 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 |
| DE4108029A1 (de) * | 1991-03-13 | 1992-09-17 | Bayer Ag | Triazinyl-substituierte acrylsaeureester |
| AU1354292A (en) | 1991-03-18 | 1992-10-21 | Pentapharm Ag | Parasubstituted phenylalanine derivates |
| 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 |
| AU3420693A (en) | 1991-12-24 | 1993-07-28 | Fred Hutchinson Cancer Research Center | Competitive inhibition of high-avidity alpha4-beta1 receptor using tripeptide ldv |
| EP0633881B1 (fr) * | 1992-03-11 | 2003-10-29 | Narhex Limited | Derives amines d'hydrocarbures a substitution oxo et hydroxy |
| 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 |
| TW530047B (en) * | 1994-06-08 | 2003-05-01 | 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 |
| DE69530392D1 (de) | 1994-07-11 | 2003-05-22 | 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 |
| US6028223A (en) * | 1995-08-30 | 2000-02-22 | G. D. Searle & Co. | Meta-guanidine, urea, thiourea or azacyclic amino benzoic acid compounds and derivatives thereof |
| ZA968183B (en) * | 1995-09-29 | 1997-04-25 | Sankyo Co | 13-Substituted milbemycin 5-oxime derivatives their preparation and their use against insects and other pests |
| 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 |
| KR100459978B1 (ko) | 1996-06-21 | 2005-01-15 | 다께다 케미칼 인더스트리즈,리미티드 | 펩티드제조방법 |
| JP2000516575A (ja) | 1996-06-28 | 2000-12-12 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフトング | インテグリンインヒビターとしてのフェニルアラニン誘導体 |
| 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 |
| DE19647381A1 (de) * | 1996-11-15 | 1998-05-20 | Hoechst Ag | Neue Heterocyclen als Inhibitoren der Leukozytenadhäsion und VLA-4-Antagonisten |
| KR20000069074A (ko) | 1996-11-22 | 2000-11-25 | 진 엠. 듀발 | Ｎ-(아릴/헤테로아릴아세틸) 아미노산 에스테르, 이를 함유한 약제학적 조성물 및 이를 사용한 β-아밀로이드 펩티드의 방출 및(또는) 합성 억제 방법 |
| AU6264898A (en) | 1997-02-04 | 1998-08-25 | 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 |
| WO1998053817A1 (fr) | 1997-05-29 | 1998-12-03 | Merck & Co., Inc. | Acide biarylalcanoique utilise en tant qu'inhibiteur de l'adhesion cellulaire |
| EP1001764A4 (fr) | 1997-05-29 | 2005-08-24 | Merck & Co Inc | Composes d'amide heterocycliques utilises en tant qu'inhibiteurs de l'adhesion cellulaire |
| 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 |
| HUP0002495A3 (en) | 1997-07-31 | 2001-01-29 | American Home Prod | Dipeptide and related compounds which inhibit leukocyte adhesion mediated by vla-4, pharmaceutical compositions comprising thereof and their use |
| NZ502582A (en) | 1997-07-31 | 2002-07-26 | American Home Prod | Substituted phenylalanine type compounds which inhibit leukocyte adhesion mediated by VLA-4 |
| IL133641A0 (en) | 1997-07-31 | 2001-04-30 | Elan Pharm Inc | Compounds which inhibit leukocyte adhesion mediated by vla-4 |
| IL134550A (en) | 1997-08-22 | 2005-12-18 | Hoffmann La Roche | History of N - aroylphenylalanine, their use in drug preparation and as a drug |
| PT1005446E (pt) | 1997-08-22 | 2004-06-30 | Hoffmann La Roche | Derivados de n-aroilfenilalanina |
| 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 |
| TR200100141T2 (tr) | 1998-04-16 | 2001-06-21 | Texas Biotechnology Corporation | İntegrinlerin reseptörlerine bağlanmasını engelleyen bileşikler |
| GB9821061D0 (en) | 1998-09-28 | 1998-11-18 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9825652D0 (en) | 1998-11-23 | 1999-01-13 | Celltech Therapeutics Ltd | Chemical compounds |
| WO2000043372A1 (fr) * | 1999-01-22 | 2000-07-27 | Elan Pharmaceuticals, Inc. | Derives d'acyle utiles pour traiter des affections associees a vla-4 |
| KR100711840B1 (ko) * | 1999-01-22 | 2007-05-02 | 엘란 파마슈티칼스, 인크. | Ｖｌａ-4 관련 질환 치료용 아실 유도체 |
| PE20020384A1 (es) | 2000-07-21 | 2002-05-28 | Schering Corp | PEPTIDOS COMO INHIBIDORES DE LA PROTEASA SERINA NS3/NS4a DEL VIRUS DE LA HEPATITIS C |
| TWI281470B (en) * | 2002-05-24 | 2007-05-21 | Elan Pharm Inc | Heterocyclic compounds which inhibit leukocyte adhesion mediated by alpha4 integrins |
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- 2003-05-27 DK DK03731419T patent/DK1507775T3/da active
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