SK286736B6 - Inhibítory kaspázy, farmaceutická kompozícia, ktorá ich obsahuje, a ich použitie - Google Patents
Inhibítory kaspázy, farmaceutická kompozícia, ktorá ich obsahuje, a ich použitie Download PDFInfo
- Publication number
- SK286736B6 SK286736B6 SK1382-2000A SK13822000A SK286736B6 SK 286736 B6 SK286736 B6 SK 286736B6 SK 13822000 A SK13822000 A SK 13822000A SK 286736 B6 SK286736 B6 SK 286736B6
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- Slovakia
- Prior art keywords
- alkyl
- mmol
- aryl
- group
- ring system
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- 239000003112 inhibitor Substances 0.000 title abstract description 25
- 239000008194 pharmaceutical composition Substances 0.000 title abstract description 25
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- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 61
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- 125000004122 cyclic group Chemical group 0.000 claims description 43
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 36
- 125000003118 aryl group Chemical group 0.000 claims description 31
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- 125000001072 heteroaryl group Chemical group 0.000 claims description 23
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
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UA (2) | UA74133C2 (fr) |
WO (1) | WO1999047545A2 (fr) |
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Families Citing this family (77)
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EP2261233A3 (fr) * | 1998-03-19 | 2011-04-20 | Vertex Pharmaceuticals Incorporated | Inhibiteurs de caspase |
US6242422B1 (en) * | 1998-10-22 | 2001-06-05 | Idun Pharmacueticals, Inc. | (Substituted)Acyl dipeptidyl inhibitors of the ice/ced-3 family of cysteine proteases |
US7157430B2 (en) | 1998-10-22 | 2007-01-02 | Idun Pharmaceuticals, Inc. | (Substituted)acyl dipeptidyl inhibitors of the ICE/CED-3 family of cysteine proteases |
US7326542B2 (en) | 1998-12-02 | 2008-02-05 | Princeton University | Compositions and methods for regulating bacterial pathogenesis |
US6720415B2 (en) | 1998-12-02 | 2004-04-13 | Princeton University | Compositions and methods for regulating bacterial pathogenesis |
WO2001027085A1 (fr) * | 1999-10-13 | 2001-04-19 | Merck Frosst Canada & Co. | Utilisation de comme inhibiteurs de la caspase-3 nicotinyl aspartyl ketones as inhibitors of caspase-3 |
US6395767B2 (en) | 2000-03-10 | 2002-05-28 | Bristol-Myers Squibb Company | Cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV and method |
US6525024B1 (en) | 2000-04-17 | 2003-02-25 | Idun Pharmaceuticals, Inc. | Inhibitors of the ICE/ced-3 family of cysteine proteases |
AU2001259734A1 (en) | 2000-05-10 | 2001-11-20 | Princeton University | Compounds and methods for regulating bacterial growth and pathogenesis |
PE20011350A1 (es) | 2000-05-19 | 2002-01-15 | Vertex Pharma | PROFARMACO DE UN INHIBIDOR DE ENZIMA CONVERTIDORA DE INTERLEUCINA-1ß (ICE) |
AU2001290795A1 (en) * | 2000-09-13 | 2002-03-26 | Vertex Pharmaceuticals Incorporated | Caspase inhibitors and uses thereof |
WO2002070544A2 (fr) * | 2001-03-02 | 2002-09-12 | Idun Pharmaceuticals, Inc. | Procedes, compositions et kits pour preserver l'antigenicite |
CN1547486A (zh) | 2001-06-26 | 2004-11-17 | 抗opgl抗体 | |
EP1485107A1 (fr) * | 2002-02-11 | 2004-12-15 | Vertex Pharmaceuticals Incorporated | Phospholipides tels que des promedicaments inhibiteurs de caspases |
WO2003075853A2 (fr) | 2002-03-08 | 2003-09-18 | Bristol-Myers Squibb Company | Derives cycliques servant de modulateurs de l'activite du recepteur de la chimiokine |
FR2839309B1 (fr) | 2002-05-03 | 2004-07-23 | Aventis Pharma Sa | Nouveaux derives de l'acide hexahydro-pyridazine-3- carboxylique, chimiotheques les contenant, leur utilisation comme medicaments, compositions pharmaceutiques les contenant et leurs procedes de preparation |
US7001899B2 (en) | 2002-06-10 | 2006-02-21 | The Procter & Gamble Company | Interleukin converting enzyme inhibitors |
WO2004022536A1 (fr) * | 2002-09-04 | 2004-03-18 | Glenmark Pharmaceuticals Limited | Nouveaux composes amides heterocycliques utilises pour le traitement d'affections inflammatoires et allergiques; procede permettant de les fabriquer et compositions pharmaceutiques les contenant |
AR041173A1 (es) | 2002-09-06 | 2005-05-04 | Amgen Inc | Aniticuerpo monoclonal anti- il- 1r1 humano terapeutico |
AU2003269317B2 (en) | 2002-10-23 | 2009-10-29 | Glenmark Pharmaceuticals Ltd. | Novel tricyclic compounds useful for the treatment of inflammatory and allergic disorders: process for their preparation and pharmaceutical compositions containing them |
FR2846969A1 (fr) * | 2002-11-08 | 2004-05-14 | Salles Jean Pierre | Nouveaux vecteurs moleculaires amphiphiles fluorocarbones a usage biomedical et medical |
FR2847160A1 (fr) * | 2002-11-20 | 2004-05-21 | Oreal | Composition capillaire contenant un compose pyrasol-carboxamide, son utilisation pour stimuler la pousse des cheveux et/ou freiner leur chute |
JP2006519755A (ja) * | 2002-11-20 | 2006-08-31 | ロレアル | ピラゾール−カルボキシアミドを含有する毛髪の手入れ用又は睫毛用の組成物、毛髪及び睫毛の成長を刺激し、及び/又は抜毛を防止するためのそれらの使用 |
WO2004089940A1 (fr) | 2003-04-11 | 2004-10-21 | Glenmark Pharmaceuticals S.A. | Nouveaux composes heterocycliques pour le traitement des affections inflammatoires et allergiques, leur procede de preparation et compositions pharmaceutiques les contenant |
AU2003902704A0 (en) * | 2003-05-29 | 2003-06-19 | Crc For Waste Management And Pollution Control Limited Of Unsw | Process for producing a nanoscale zero-valent metal |
EP1696894A1 (fr) * | 2003-12-01 | 2006-09-06 | Vertex Pharmaceuticals Incorporated | Traitement de maladies infectieuses utilisant des inhibiteurs de l'enzyme de conversion de l'interleukine-1 (ice) |
ATE422350T1 (de) * | 2003-12-12 | 2009-02-15 | Straetmans Chemische Produkte | Anisinsäure und glyceride enthaltende zusammensetzungen |
AU2011226946B2 (en) * | 2004-02-27 | 2012-05-03 | Vertex Pharmaceuticals Incoporated | Caspase Inhibitors and Uses Thereof |
WO2005085236A2 (fr) | 2004-02-27 | 2005-09-15 | Vertex Pharmaceuticals Incorporated | Inhibiteurs de la caspase et leurs utilisations |
CN1942466B (zh) * | 2004-02-27 | 2011-02-23 | 沃泰克斯药物股份有限公司 | 天冬氨酸特异性半胱氨酸蛋白酶抑制剂及其用途 |
ES2532967T3 (es) * | 2004-03-12 | 2015-04-06 | Vertex Pharmaceuticals Incorporated | Proceso y productos intermedios para la preparación de inhibidores de la acetal caspasa aspártica |
US8273794B2 (en) * | 2004-05-14 | 2012-09-25 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
AU2012200214B2 (en) * | 2004-05-14 | 2013-10-24 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
AU2005247409B2 (en) * | 2004-05-15 | 2011-11-10 | Vertex Pharmaceuticals Incorporated | Treating seizures using ICE inhibitors |
GB0411056D0 (en) | 2004-05-18 | 2004-06-23 | Novartis Ag | Organic compounds |
CA2567080A1 (fr) * | 2004-05-27 | 2005-12-15 | Vertex Pharmaceuticals Incorporated | Traitement de maladies a l'aide d'inhibiteurs de l'ice |
EP2457895A1 (fr) * | 2004-07-12 | 2012-05-30 | Idun Pharmaceuticals, Inc. | Analogue de tétrapeptides |
ES2312012T3 (es) * | 2004-09-17 | 2009-02-16 | Biomas Ltd. | Nuevos compuestos de telurio y su uso como inmunomodulares. |
CA2583497A1 (fr) | 2004-10-13 | 2006-04-20 | Glenmark Pharmaceuticals S.A. | Procede de preparation de n-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-8-methanesulfonamido-dibenzo[b,d]furan-1-carboxamide |
WO2006064355A2 (fr) | 2004-12-17 | 2006-06-22 | Glenmark Pharmaceuticals S.A. | Nouveaux composes heterocycliques utiles pour le traitement de troubles inflammatoires et allergiques |
CN101124229B (zh) | 2004-12-17 | 2012-07-18 | 格兰马克药品股份有限公司 | 用于治疗炎性和过敏性障碍的新杂环化合物 |
JP4673068B2 (ja) * | 2005-01-19 | 2011-04-20 | 独立行政法人科学技術振興機構 | Th1型アレルギー疾患治療用組成物 |
DE102005017116A1 (de) * | 2005-04-13 | 2006-10-26 | Novartis Ag | Hemmstoffe für Inhibitoren von Apoptose Proteinen (IAP) |
ATE529430T1 (de) | 2005-07-28 | 2011-11-15 | Vertex Pharma | Caspase-hemmer-propharmaka |
PE20070684A1 (es) | 2005-11-14 | 2007-08-06 | Amgen Inc | MOLECULAS QUIMERICAS DE ANTICUERPO RANKL-PTH/PTHrP |
US20100068150A1 (en) * | 2006-07-07 | 2010-03-18 | The Board Of Trustees Of The Leland Stanford Junior University | Selective Caspase Inhibitors |
US8754107B2 (en) * | 2006-11-17 | 2014-06-17 | Abbvie Inc. | Aminopyrrolidines as chemokine receptor antagonists |
US8084862B2 (en) | 2007-09-20 | 2011-12-27 | International Business Machines Corporation | Interconnect structures with patternable low-k dielectrics and method of fabricating same |
US7709370B2 (en) * | 2007-09-20 | 2010-05-04 | International Business Machines Corporation | Spin-on antireflective coating for integration of patternable dielectric materials and interconnect structures |
US8618663B2 (en) | 2007-09-20 | 2013-12-31 | International Business Machines Corporation | Patternable dielectric film structure with improved lithography and method of fabricating same |
US8343458B2 (en) * | 2008-04-03 | 2013-01-01 | The Board Of Trustees Of The Leland Stanford Junior University | Probes for in vivo targeting of active cysteine proteases |
WO2009144455A2 (fr) * | 2008-05-27 | 2009-12-03 | Imperial Innovations Limited | Procédé de production de supports poreux à partir de verre frittable |
US20110152343A1 (en) * | 2009-12-22 | 2011-06-23 | Functional Genetics, Inc. | Protease inhibitors and broad-spectrum antiviral |
GB201001070D0 (en) | 2010-01-22 | 2010-03-10 | St George's Hospital Medical School | Theraputic compounds and their use |
US9365612B2 (en) | 2010-01-29 | 2016-06-14 | United States Of America As Represented By The Secretary, Department Of Health And Human Services | Caspase inhibitors |
GB201011411D0 (en) | 2010-07-06 | 2010-08-18 | St Georges Hosp Medical School | Therapeutic compounds and their use |
JP6006908B2 (ja) | 2010-11-05 | 2016-10-12 | ブランダイス ユニバーシティBrandeis University | Ice阻害化合物およびその使用 |
US9956260B1 (en) | 2011-07-22 | 2018-05-01 | The J. David Gladstone Institutes | Treatment of HIV-1 infection and AIDS |
EP2766347B1 (fr) | 2011-10-14 | 2016-05-04 | Bristol-Myers Squibb Company | Composés de tétrahydroisoquinoléine substitués en tant qu'inhibiteurs du facteur xia |
KR101937514B1 (ko) | 2011-10-14 | 2019-01-10 | 브리스톨-마이어스 스큅 컴퍼니 | 인자 xia 억제제로서의 치환된 테트라히드로이소퀴놀린 화합물 |
ES2572908T3 (es) | 2011-10-14 | 2016-06-03 | Bristol-Myers Squibb Company | Compuestos de tetrahidroisoquinolina sustituidos como inhibidores del factor XIa |
KR20150046259A (ko) * | 2012-08-23 | 2015-04-29 | 앨리오스 바이오파마 인크. | 파라믹소바이러스 바이러스성 감염의 치료용 화합물 |
EP2906551B1 (fr) | 2012-10-12 | 2018-02-28 | Bristol-Myers Squibb Company | Formes cristallines d'un inhibiteur de facteur xia |
WO2014059202A1 (fr) | 2012-10-12 | 2014-04-17 | Bristol-Myers Squibb Company | Composés de tétrahydroisoquinoléine substitués par guanidine comme inhibiteurs du facteur xia |
WO2014059214A1 (fr) | 2012-10-12 | 2014-04-17 | Bristol-Myers Squibb Company | Composés de tétrahydroisoquinoléine à substitution guanidine et amine utilisés comme inhibiteurs du facteur xia |
JP6479763B2 (ja) | 2013-03-25 | 2019-03-06 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 第xia因子阻害剤としての置換アゾール含有のテトラヒドロイソキノリン |
US20170002006A1 (en) | 2014-01-31 | 2017-01-05 | Bristol-Myers Squibb Company | Macrocycles with hetrocyclic p2' groups as factor xia inhibitors |
NO2760821T3 (fr) | 2014-01-31 | 2018-03-10 | ||
US9737556B2 (en) | 2014-06-13 | 2017-08-22 | Trustees Of Tufts College | FAP-activated therapeutic agents, and uses related thereto |
HRP20230854T1 (hr) | 2014-06-13 | 2023-11-10 | Bach Biosciences, Llc | Fap-aktivirana terapeutska sredstva i s njima povezane uporabe |
ES2714283T3 (es) | 2014-09-04 | 2019-05-28 | Bristol Myers Squibb Co | Macrociclos de diamida que son inhibidores de FXIa |
US9453018B2 (en) | 2014-10-01 | 2016-09-27 | Bristol-Myers Squibb Company | Pyrimidinones as factor XIa inhibitors |
MX2021006326A (es) | 2015-09-17 | 2022-12-16 | Inhibidores de pcna. | |
WO2018016547A1 (fr) * | 2016-07-22 | 2018-01-25 | キッセイ薬品工業株式会社 | Dérivé de pyrrolidine |
WO2018112626A1 (fr) | 2016-12-23 | 2018-06-28 | Andrea Leblanc | Inhibition de la caspase-1 et ses utilisations dans la prévention et le traitement d'états neurologiques |
WO2020035482A1 (fr) | 2018-08-13 | 2020-02-20 | Iltoo Pharma | Combinaison d'interleukine 2 et d'un inhibiteur de l'interleukine 1, conjugués et utilisations thérapeutiques de celle-ci |
EP4251140A1 (fr) * | 2020-11-25 | 2023-10-04 | Lysosomal and Rare Disorders Research and Treatment Center, Inc. | Inhibition de voie de caspase en tant que traitement pour des troubles du stockage lysosomal |
Family Cites Families (80)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2973111A (en) * | 1958-02-11 | 1961-02-28 | Dempster Brothers Inc | Compaction bodies |
US6204261B1 (en) * | 1995-12-20 | 2001-03-20 | Vertex Pharmaceuticals Incorporated | Inhibitors of interleukin-1β Converting enzyme inhibitors |
US5874424A (en) | 1995-12-20 | 1999-02-23 | Vertex Pharmaceuticals Incorporated | Inhibitors of interleukin-1β converting enzyme |
US4465679A (en) | 1983-01-31 | 1984-08-14 | Usv Pharmaceutical Corporation | 1,2-Diaza-3-one compounds, their use in treating hypertension and pharmaceutical compositions thereof |
IL72523A (en) | 1983-08-12 | 1988-06-30 | Takeda Chemical Industries Ltd | 3-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine derivatives,their production and pharmaceutical compositions containing them |
US5055451A (en) | 1986-12-22 | 1991-10-08 | Syntex Inc. | Aryloxy and arylacyloxy methyl ketones as thiol protease inhibitors |
US5158936A (en) | 1986-12-22 | 1992-10-27 | Syntex (U.S.A.) Inc. | Aryloxy and arylacyloxy methyl ketones as thiol protease inhibitors |
US5008245A (en) | 1988-10-27 | 1991-04-16 | University Of Kentucky Research Foundation | Novel peptidyl carbamate inhibitors of the enzyme elastase |
CA2021660A1 (fr) | 1989-07-26 | 1991-01-27 | Philippe Bey | Inhibiteurs de la peptidose |
NZ235155A (en) | 1989-09-11 | 1993-04-28 | Merrell Dow Pharma | Peptidase substrates in which the carboxy terminal group has been replaced by a tricarbonyl radical |
US5416013A (en) | 1990-04-04 | 1995-05-16 | Sterling Winthrop Inc. | Interleukin 1β protease and interleukin 1β protease inhibitors |
AU7775991A (en) | 1990-04-04 | 1991-10-30 | Immunex Corporation | Interleukin 1beta protease |
EP0503561B1 (fr) | 1991-03-15 | 1998-10-28 | Hoechst Aktiengesellschaft | Procédé pour l'accouplement diastereoselective reductif des alpha aminoaldehydes homochirales |
DE69226820T2 (de) * | 1991-06-21 | 1999-05-12 | Merck & Co., Inc., Rahway, N.J. | Peptidylderivate als Inhibitoren von Interleukin-1B-konvertierenden Enzymen |
JP3190431B2 (ja) | 1991-07-01 | 2001-07-23 | 三菱化学株式会社 | ケトン誘導体 |
DE69229252T2 (de) | 1991-08-16 | 1999-12-16 | Merck & Co., Inc. | DNS, welche das Interleukin-1B-Vorläufer-Converting-Enzym kodiert |
EP0533226A3 (en) | 1991-08-16 | 1993-08-18 | Merck & Co. Inc. | Novel chromophore containing compounds |
US6348570B1 (en) | 1991-08-16 | 2002-02-19 | Merck & Co., Inc. | Chromophore containing compounds and their use in determining interleukin-1β convertase activity |
US5278061A (en) | 1991-08-16 | 1994-01-11 | Merck & Co., Inc. | Affinity chromatography matrix useful in purifying interleukin-1β converting enzyme |
WO1993005071A1 (fr) | 1991-08-30 | 1993-03-18 | Sterling Winthrop Inc. | INTERLEUKINE 1β PROTEASE ET INHIBITEURS D'INTERLEUKINE 1β PROTEASE |
EP0541946B1 (fr) | 1991-10-07 | 1996-07-17 | Hoechst Aktiengesellschaft | Procédé de couplage-pinacol réductant diastéréosélectif d'alpha-aminoaldéhydes |
GB9123326D0 (en) | 1991-11-04 | 1991-12-18 | Sandoz Ltd | Improvements in or relating to organic compounds |
WO1993012076A1 (fr) | 1991-12-13 | 1993-06-24 | Corvas International Inc. | Reactifs pour la synthese automatisee d'analogues peptidiques |
EP0547699A1 (fr) | 1991-12-19 | 1993-06-23 | Merck & Co. Inc. | Dérivés peptidiques comme inhibiteurs d'enzyme convertissant l'interleukine 1-bêta |
AU3479593A (en) | 1992-01-31 | 1993-09-01 | Merck & Co., Inc. | Peptidyl derivatives as inhibitors of interleukin-1beta converting enzyme |
EP0627926B1 (fr) | 1992-02-21 | 1998-08-05 | Merck & Co., Inc. (a New Jersey corp.) | DERIVES DE PEPTIDYLE UTILES COMME INHIBITEURS DE L'ENZYME CONVERTISSANT L'INTERLEUKINE-1$g(b) |
CA2136981A1 (fr) | 1992-06-24 | 1994-01-06 | Andrew D. Howard | Adn codant pour l'enzyme de conversion de l'interleukine 1.beta. precurseur |
EP0654041B1 (fr) | 1992-07-31 | 1998-07-01 | Pfizer Inc. | Derives de l'acide peptidyl 4-amino-2,2-difluoro-3-oxo-1,6-hexane-dio utilises comme agents antiinflammatoires |
CA2109646C (fr) | 1992-11-24 | 2000-03-07 | Gaston O. Daumy | Peptides para-nitroanilides |
EP0618223A3 (fr) | 1993-03-08 | 1996-06-12 | Sandoz Ltd | Peptides inhibent la libération d'interleukine 1-bêta utiles comme agents antiinflammatoires. |
CA2122227A1 (fr) | 1993-04-29 | 1994-10-30 | Roland E. Dolle | Analogues de peptides utilises comme inhibiteurs irreversibles de la protease de l'interleukine-1.beta. |
US5462939A (en) | 1993-05-07 | 1995-10-31 | Sterling Winthrop Inc. | Peptidic ketones as interleukin-1β-converting enzyme inhibitors |
US5411985A (en) | 1993-05-17 | 1995-05-02 | Merck & Co., Inc. | Gamma-pyrone-3-acetic acid as an inhibitor or interleukin-1 β inventory enzyme |
JPH0789951A (ja) | 1993-06-03 | 1995-04-04 | Sterling Winthrop Inc | インターロイキン−1β転換酵素阻害剤 |
DK0644197T3 (da) | 1993-06-04 | 1999-06-07 | Vertex Pharma | Peptidphosphinyloxymethylketoner som inhibitorer af interleukin-1beta-konverterende enzymer |
WO1995000160A1 (fr) | 1993-06-24 | 1995-01-05 | The General Hospital Corporation | Genes regulateurs de la mort cellulaire programmee et proteines |
AU7714594A (en) | 1993-08-13 | 1995-03-14 | Merck & Co., Inc. | Substituted ketone derivatives as inhibitors of interleukin-1beta converting enzyme |
DE59405370D1 (de) * | 1993-11-11 | 1998-04-09 | Basf Ag | P-Hydroxyanilinderivate, Verfahren zu ihrer Herstellung und ihre Verwendung zur Bekämpfung von Schadpilzen oder Schädlingen |
US5486623A (en) | 1993-12-08 | 1996-01-23 | Prototek, Inc. | Cysteine protease inhibitors containing heterocyclic leaving groups |
US5714484A (en) | 1993-12-08 | 1998-02-03 | Prototek, Inc. | α-(1,3-dicarbonylenol ether) methyl ketones as cysteine protease inhibitors |
CN1504462A (zh) | 1994-03-31 | 2004-06-16 | ������˹ҩƷ��˾ | 作为白细胞介素抑制剂的嘧啶基衍生物 |
CN1147201A (zh) | 1994-04-29 | 1997-04-09 | 圣诺菲温特洛普公司 | 用作IL-Iβ蛋白酶抑制剂的卤甲基酰胺 |
US5492824A (en) | 1994-05-12 | 1996-02-20 | Basf Ag | Ice and ice-like compositions and methods of making same |
US5552400A (en) | 1994-06-08 | 1996-09-03 | Sterling Winthrop Inc. | Fused-bicyclic lactams as interleukin-1β converting enzyme inhibitors |
US5847135A (en) | 1994-06-17 | 1998-12-08 | Vertex Pharmaceuticals, Incorporated | Inhibitors of interleukin-1β converting enzyme |
US6057119A (en) | 1994-06-17 | 2000-05-02 | Vertex Pharmaceuticals, Incorporated | Crystal structure and mutants of interleukin-1β converting enzyme |
US5716929A (en) * | 1994-06-17 | 1998-02-10 | Vertex Pharmaceuticals, Inc. | Inhibitors of interleukin-1β converting enzyme |
US5756466A (en) | 1994-06-17 | 1998-05-26 | Vertex Pharmaceuticals, Inc. | Inhibitors of interleukin-1β converting enzyme |
US5565430A (en) | 1994-08-02 | 1996-10-15 | Sterling Winthrop Inc. | Azaaspartic acid analogs as interleukin-1β converting enzyme inhibitors |
GB2292149A (en) * | 1994-08-09 | 1996-02-14 | Ferring Res Ltd | Peptide inhibitors of pro-interleukin-1beta converting enzyme |
US5498616A (en) | 1994-11-04 | 1996-03-12 | Cephalon, Inc. | Cysteine protease and serine protease inhibitors |
TW394764B (en) | 1995-02-14 | 2000-06-21 | Mitsubishi Chemcal Corp | Oxygen-containing heterocyclic derivatives |
CA2215211A1 (fr) * | 1995-03-31 | 1996-10-03 | Takeda Chemical Industries, Ltd. | Inhibiteur de la protease de cysteine |
JPH09165360A (ja) * | 1995-03-31 | 1997-06-24 | Takeda Chem Ind Ltd | システインプロテアーゼ阻害剤 |
US5798442A (en) | 1995-04-21 | 1998-08-25 | Merck Frosst Canada, Inc. | Peptidyl derivatives as inhibitors of pro-apoptotic cysteine proteinases |
WO1997007805A1 (fr) | 1995-08-31 | 1997-03-06 | Smithkline Beecham Corporation | Enzyme de conversion d'interleukines et apoptose |
WO1997008174A1 (fr) | 1995-08-31 | 1997-03-06 | Smithkline Beecham Corporation | Enzyme de conversion d'interleukine et apoptose |
EP0761680A3 (fr) | 1995-09-12 | 1999-05-06 | Ono Pharmaceutical Co., Ltd. | Composés de tétrazole ayant une activité inhibante d'enzyme convertissant l'Interleukine-1bêta |
US5744451A (en) | 1995-09-12 | 1998-04-28 | Warner-Lambert Company | N-substituted glutamic acid derivatives with interleukin-1 β converting enzyme inhibitory activity |
WO1997024339A1 (fr) | 1995-12-27 | 1997-07-10 | Ono Pharmaceutical Co., Ltd. | Derives de tetrazole et medicaments les contenant a titre d'ingredients actifs |
AU3359697A (en) | 1996-07-08 | 1998-02-02 | Yamanouchi Pharmaceutical Co., Ltd. | Bone resorption inhibitors |
WO1998004539A1 (fr) | 1996-07-29 | 1998-02-05 | Mitsubishi Chemical Corporation | Derives heterocycliques oxygenes |
WO1998011109A1 (fr) | 1996-09-12 | 1998-03-19 | Idun Pharmaceuticals, Incorporated | Nouveaux composes tricycliques permettant d'inhiber la famille de proteases ice/ced-3 |
WO1998010778A1 (fr) | 1996-09-12 | 1998-03-19 | Idun Pharmaceuticals, Inc. | INHIBITION DE L'APOPTOSE AU MOYEN D'INHIBITEURS DE LA FAMILLE CED-3/ICE (ENZYME DE CONVERSION DE L'INTERLEUKINE-1β) |
CN1234038A (zh) * | 1996-09-12 | 1999-11-03 | 伊邓药品公司 | 作为ICE/ced-3类半胱氨酸蛋白酶抑制剂的C-末端修饰的(N-取代)-2-吲哚基二肽 |
US5869519A (en) * | 1996-12-16 | 1999-02-09 | Idun Pharmaceuticals, Inc. | C-terminal modified (n-substituted)-2-indolyl dipeptides as inhibitors of the ICE/ced-3 family of cysteine proteases |
US5968927A (en) * | 1996-09-20 | 1999-10-19 | Idun Pharmaceuticals, Inc. | Tricyclic compounds for the inhibition of the ICE/ced-3 protease family of enzymes |
US5877197A (en) * | 1996-12-16 | 1999-03-02 | Karanewsky; Donald S. | C-terminal modified (N-substituted)-2-indolyl dipeptides as inhibitors of the ICE/ced-3 family of cysteine proteases |
US6184244B1 (en) * | 1996-12-16 | 2001-02-06 | Idun Pharmaceuticals, Inc. | C-terminal modified (N-substituted)-2-indolyl dipeptides as inhibitors of the ICE/ced-3 family of cysteine proteases |
US6054487A (en) * | 1997-03-18 | 2000-04-25 | Basf Aktiengesellschaft | Methods and compositions for modulating responsiveness to corticosteroids |
HUP9700816A3 (en) | 1997-04-28 | 1999-06-28 | Gyogyszerkutato Intezet | 3(r)-3-amino-4-carboxy-butiraldehyde derivatives inhibiting release of interleukin-1-beta |
US6184210B1 (en) * | 1997-10-10 | 2001-02-06 | Cytovia, Inc. | Dipeptide apoptosis inhibitors and the use thereof |
WO1999022619A1 (fr) * | 1997-10-31 | 1999-05-14 | Kimberly-Clark Worldwide, Inc. | Materiaux crepes non tisses et doublure |
EP2261233A3 (fr) * | 1998-03-19 | 2011-04-20 | Vertex Pharmaceuticals Incorporated | Inhibiteurs de caspase |
US6197750B1 (en) * | 1998-07-02 | 2001-03-06 | Idun Pharmaceuticals, Inc. | C-terminal modified oxamyl dipeptides as inhibitors of the ICE/ced-3 family of cysteine proteases |
US6242422B1 (en) * | 1998-10-22 | 2001-06-05 | Idun Pharmacueticals, Inc. | (Substituted)Acyl dipeptidyl inhibitors of the ice/ced-3 family of cysteine proteases |
PE20011350A1 (es) * | 2000-05-19 | 2002-01-15 | Vertex Pharma | PROFARMACO DE UN INHIBIDOR DE ENZIMA CONVERTIDORA DE INTERLEUCINA-1ß (ICE) |
CA2545733A1 (fr) * | 2003-11-10 | 2005-05-26 | Vertex Pharmaceuticals Incorporated | Methodes de controle de l'il-18 |
WO2005085236A2 (fr) * | 2004-02-27 | 2005-09-15 | Vertex Pharmaceuticals Incorporated | Inhibiteurs de la caspase et leurs utilisations |
CA2567080A1 (fr) * | 2004-05-27 | 2005-12-15 | Vertex Pharmaceuticals Incorporated | Traitement de maladies a l'aide d'inhibiteurs de l'ice |
-
1999
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2000
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2001
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2002
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2006
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2008
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MK4A | Patent expired |
Expiry date: 20190319 |