UA72733C2 - Sulfonamide derivatives as precursors of aspartyl protease inhibitors - Google Patents
Sulfonamide derivatives as precursors of aspartyl protease inhibitors Download PDFInfo
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- UA72733C2 UA72733C2 UA2000074456A UA2000074456A UA72733C2 UA 72733 C2 UA72733 C2 UA 72733C2 UA 2000074456 A UA2000074456 A UA 2000074456A UA 2000074456 A UA2000074456 A UA 2000074456A UA 72733 C2 UA72733 C2 UA 72733C2
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- 238000000034 method Methods 0.000 claims abstract description 32
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 30
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- 125000000623 heterocyclic group Chemical group 0.000 claims description 31
- 125000001424 substituent group Chemical group 0.000 claims description 25
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- 125000005842 heteroatom Chemical group 0.000 claims description 20
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P31/12—Antivirals
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
- C07C311/18—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by nitrogen atoms, not being part of nitro or nitroso groups
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- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/18—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/20—Oxygen atoms
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/65515—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
- C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
- C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
- C07F9/65842—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring
- C07F9/65844—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring the phosphorus atom being part of a five-membered ring which may be condensed with another ring system
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- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/02—Acyclic radicals, not substituted by cyclic structures
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/998,050 US6436989B1 (en) | 1997-12-24 | 1997-12-24 | Prodrugs of aspartyl protease inhibitors |
PCT/US1998/004595 WO1999033815A1 (en) | 1997-12-24 | 1998-03-09 | Sulphonamide derivatives as prodrugs of aspartyl protease inhibitors |
Publications (1)
Publication Number | Publication Date |
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UA72733C2 true UA72733C2 (en) | 2005-04-15 |
Family
ID=25544691
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
UA2000074456A UA72733C2 (en) | 1997-12-24 | 1998-09-03 | Sulfonamide derivatives as precursors of aspartyl protease inhibitors |
Country Status (43)
Families Citing this family (158)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040122000A1 (en) * | 1981-01-07 | 2004-06-24 | Vertex Pharmaceuticals Incorporated. | Inhibitors of aspartyl protease |
UA59384C2 (uk) * | 1996-12-20 | 2003-09-15 | Пфайзер, Інк. | Похідні сульфонамідів та амідів як агоністи простагландину, фармацевтична композиція та способи лікування на їх основі |
US6436989B1 (en) * | 1997-12-24 | 2002-08-20 | Vertex Pharmaceuticals, Incorporated | Prodrugs of aspartyl protease inhibitors |
PL204628B1 (pl) | 1998-06-02 | 2010-01-29 | Osi Pharmaceuticals | Pochodna pirolo[2,3d]pirymidyny, jej zastosowanie i sposoby wytwarzania tej pochodnej i preparaty farmaceutyczne |
US6878716B1 (en) | 1998-06-02 | 2005-04-12 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A1 receptor and uses thereof |
US6686366B1 (en) | 1998-06-02 | 2004-02-03 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A3 receptor and uses thereof |
GB9815567D0 (en) * | 1998-07-18 | 1998-09-16 | Glaxo Group Ltd | Antiviral compound |
AU6329599A (en) * | 1998-09-28 | 2000-04-17 | Glaxo Group Limited | Antiviral combinations comprising (s)-2-ethyl -7-fluoro -3-oxo-3, 4-dihydro -2h-quinoxaline -1-carboxylic acid isopropyl ester |
GB9914821D0 (en) * | 1999-06-24 | 1999-08-25 | Glaxo Group Ltd | Compounds |
US7160890B2 (en) | 1999-12-02 | 2007-01-09 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A3 receptor and uses thereof |
US6664252B2 (en) | 1999-12-02 | 2003-12-16 | Osi Pharmaceuticals, Inc. | 4-aminopyrrolo[2,3-d]pyrimidine compounds specific to adenosine A2a receptor and uses thereof |
US6680322B2 (en) | 1999-12-02 | 2004-01-20 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A1 receptors and uses thereof |
US6680324B2 (en) | 2000-12-01 | 2004-01-20 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A1 receptors and uses thereof |
US6673802B2 (en) | 2000-12-01 | 2004-01-06 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A3 receptor and uses thereof |
ATE343567T1 (de) | 2001-02-14 | 2006-11-15 | Tibotec Pharm Ltd | Breitspektrum 2-(substituierte-amino)- benzothiazol-sulfonamide hiv protease inhibitoren |
PL367084A1 (en) | 2001-04-09 | 2005-02-21 | Tibotec Pharmaceuticals Ltd. | Broadspectrum 2-(substituted-amino)-benzoxazole sulfonamide hiv protease inhibitors |
AU2002310818B2 (en) | 2001-05-11 | 2007-12-13 | Tibotec Pharmaceuticals Ltd. | Broadspectrum 2-amino-benzoxazole sulfonamide HIV protease inhibitors |
US7576084B2 (en) * | 2001-10-12 | 2009-08-18 | Choongwae Pharma Corporation | Reverse-turn mimetics and method relating thereto |
EP1450811B1 (de) | 2001-11-30 | 2009-10-21 | OSI Pharmaceuticals, Inc. | Verbindungen, die für Adenosin A1 und A3 Rezeptoren spezifisch sind, und deren Anwendungen |
AR037797A1 (es) * | 2001-12-12 | 2004-12-01 | Tibotec Pharm Ltd | Combinacion de inhibidores de proteasa dependientes del citocromo p450 |
US20030229067A1 (en) | 2001-12-20 | 2003-12-11 | Arlindo Castelhano | Pyrrolopyrimidine A2b selective antagonist compounds, their synthesis and use |
CA2471059C (en) | 2001-12-20 | 2011-04-26 | Osi Pharmaceuticals, Inc. | Pyrimidine a2b selective antagonist compounds, their synthesis and use |
HUP0500164A3 (en) | 2001-12-21 | 2009-03-30 | Tibotec Pharm Ltd | Heterocyclic substituted benzenesulfonamides as hiv protease inhibitors and pharmaceutical compositions containing them |
US7157489B2 (en) * | 2002-03-12 | 2007-01-02 | The Board Of Trustees Of The University Of Illinois | HIV protease inhibitors |
MY142238A (en) | 2002-03-12 | 2010-11-15 | Tibotec Pharm Ltd | Broadspectrum substituted benzimidazole sulfonamide hiv protease inhibitors |
AU2003231766A1 (en) | 2002-04-26 | 2003-11-10 | Gilead Sciences, Inc. | Non nucleoside reverse transcriptase inhibitors |
PL373425A1 (en) | 2002-05-17 | 2005-08-22 | Tibotec Pharmaceuticals Ltd. | Broadspectrum substituted benzisoxazole sulfonamide hiv protease inhibitors |
KR100994759B1 (ko) | 2002-08-14 | 2010-11-16 | 티보텍 파마슈티컬즈 | 광역스펙트럼의 치환된 옥신돌 설폰아미드 hiv프로테아제 저해제 |
DE10303974A1 (de) | 2003-01-31 | 2004-08-05 | Abbott Gmbh & Co. Kg | Amyloid-β(1-42)-Oligomere, Verfahren zu deren Herstellung und deren Verwendung |
CA2425031A1 (en) * | 2003-04-01 | 2004-10-01 | Smithkline Beecham Corporation | Pharmaceutical compositions |
CA2522845A1 (en) | 2003-04-25 | 2004-11-11 | Gilead Sciences, Inc. | Kinase inhibitor phosphonate conjugates |
WO2005002626A2 (en) | 2003-04-25 | 2005-01-13 | Gilead Sciences, Inc. | Therapeutic phosphonate compounds |
US7452901B2 (en) | 2003-04-25 | 2008-11-18 | Gilead Sciences, Inc. | Anti-cancer phosphonate analogs |
WO2004096285A2 (en) | 2003-04-25 | 2004-11-11 | Gilead Sciences, Inc. | Anti-infective phosphonate conjugates |
US7470724B2 (en) | 2003-04-25 | 2008-12-30 | Gilead Sciences, Inc. | Phosphonate compounds having immuno-modulatory activity |
EP1628685B1 (de) | 2003-04-25 | 2010-12-08 | Gilead Sciences, Inc. | Antivirale phosphonate analoge |
WO2004096287A2 (en) | 2003-04-25 | 2004-11-11 | Gilead Sciences, Inc. | Inosine monophosphate dehydrogenase inhibitory phosphonate compounds |
US7407965B2 (en) | 2003-04-25 | 2008-08-05 | Gilead Sciences, Inc. | Phosphonate analogs for treating metabolic diseases |
US7432261B2 (en) | 2003-04-25 | 2008-10-07 | Gilead Sciences, Inc. | Anti-inflammatory phosphonate compounds |
JP4738333B2 (ja) * | 2003-07-09 | 2011-08-03 | パラテック ファーマシューティカルズ インコーポレイテッド | 9−アミノメチルテトラサイクリン化合物のプロドラッグ |
EP2298323A3 (de) | 2003-07-09 | 2011-05-11 | Paratek Pharmaceuticals, Inc. | Substituierte Tetracyclin-Verbindungen |
US20050119163A1 (en) * | 2003-09-18 | 2005-06-02 | The Government Of The United States Of America, As Represented By The Secretary, | SH2 domain binding inhibitors |
WO2005044279A1 (en) | 2003-10-24 | 2005-05-19 | Gilead Sciences, Inc. | Purine nucleoside phosphonate conjugates |
US7432273B2 (en) | 2003-10-24 | 2008-10-07 | Gilead Sciences, Inc. | Phosphonate analogs of antimetabolites |
US20050131042A1 (en) * | 2003-12-11 | 2005-06-16 | Flentge Charles A. | HIV protease inhibiting compounds |
US7834043B2 (en) * | 2003-12-11 | 2010-11-16 | Abbott Laboratories | HIV protease inhibiting compounds |
US8193227B2 (en) | 2003-12-11 | 2012-06-05 | Abbott Laboratories | HIV protease inhibiting compounds |
CN102627609B (zh) * | 2003-12-15 | 2016-05-04 | 默沙东公司 | 杂环天冬氨酰蛋白酶抑制剂 |
JP4936897B2 (ja) | 2003-12-18 | 2012-05-23 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 抗増殖剤としてのピリド−およびピリミドピリミジン誘導体 |
BRPI0417988A (pt) | 2003-12-22 | 2007-04-27 | Gilead Sciences Inc | análogos de fosfonato antivirais |
EP1773850B1 (de) | 2004-07-06 | 2013-01-30 | Abbott Laboratories | Prodrugs von hiv-protease-inhibitoren |
ME03423B (de) | 2004-07-27 | 2020-01-20 | Gilead Sciences Inc | Phosphonat Analoga von HIV Inhibitor Verbindungen |
US7388008B2 (en) * | 2004-08-02 | 2008-06-17 | Ambrilia Biopharma Inc. | Lysine based compounds |
ES2575871T3 (es) * | 2004-08-02 | 2016-07-01 | Ambrilia Biopharma Inc. | Composiciones farmacéuticas que comprende un compuesto a base de lisina y un agente antiviral o antirretroviral VIH |
EP1789029A2 (de) | 2004-08-30 | 2007-05-30 | Interstitial Therapeutics | Verfahern und zusammensetzungen zur behandlung von zellproliferation |
BRPI0516915A (pt) | 2004-12-01 | 2008-03-11 | Devgen Nv | derivados de tiazol substituìdos por 5-carboxamido que interagem com canais de ìons, particularmante com canais de ìons da famìlia kv |
NI200700147A (es) | 2004-12-08 | 2019-05-10 | Janssen Pharmaceutica Nv | Derivados de quinazolina inhibidores de cinasas dirigidos a multip |
MX2007006534A (es) | 2004-12-17 | 2007-07-25 | Devgen Nv | Composiciones nematicidas. |
EP2161275A1 (de) * | 2005-01-19 | 2010-03-10 | Rigel Pharmaceuticals, Inc. | Prodrugs aus 2,4-Pyrimidindiamin-Verbindungen und ihre Verwendungen |
JP2008533017A (ja) * | 2005-03-11 | 2008-08-21 | スミスクライン ビーチャム コーポレーション | Hivプロテアーゼ阻害薬 |
AR053845A1 (es) | 2005-04-15 | 2007-05-23 | Tibotec Pharm Ltd | 5-tiazolilmetil[(1s,2r)-3-[[(2-amino-6-benzoxazolil)sulfonil)](2-metilpropil)amino]-2-hidroxi-1-(fenilmetil)propil]carbamato como mejorador de farmacos metabolizados por el citocromo p450 |
US20060287316A1 (en) * | 2005-04-27 | 2006-12-21 | Ambrilia Biopharma Inc. | Method for improving pharmacokinetics of protease inhibitors and protease inhibitor precursors |
US8003627B2 (en) | 2005-10-21 | 2011-08-23 | Universiteit Antwerpen | Urokinase inhibitors |
TWI432438B (zh) | 2005-11-28 | 2014-04-01 | Tibotec Pharm Ltd | 作為hiv蛋白酶抑制劑之經取代的胺基苯基磺醯胺化合物及衍生物 |
TWI385173B (zh) | 2005-11-28 | 2013-02-11 | Tibotec Pharm Ltd | 作為hiv蛋白酶抑制劑之經取代的胺基苯基磺醯胺化合物 |
PL1954718T3 (pl) | 2005-11-30 | 2015-04-30 | Abbvie Inc | Przeciwciała skierowane przeciwko A globulomerowi, ich reszty wiążące antygeny, odpowiednie hybrydomy, kwasy nukleinowe, wektory, komórki gospodarze, sposoby wytwarzania tych przeciwciał, kompozycje zawierające te przeciwciała, zastosowania tych przeciwciał i sposoby stosowania tych przeciwciał |
DK1976877T4 (en) | 2005-11-30 | 2017-01-16 | Abbvie Inc | Monoclonal antibodies to amyloid beta protein and uses thereof |
US8227450B2 (en) * | 2005-11-30 | 2012-07-24 | Ambrilia Biopharma Inc. | Lysine-based prodrugs of aspartyl protease inhibitors and processes for their preparation |
US20100004206A1 (en) * | 2005-12-27 | 2010-01-07 | Makoto Komatsu | Water-soluble benzoazepine compound and its pharmaceutical composition |
CA2654583C (en) | 2006-07-13 | 2015-11-24 | Janssen Pharmaceutica N.V. | Mtki quinazoline derivatives |
US8557776B2 (en) | 2006-09-08 | 2013-10-15 | Bayer Pharma AG | Compounds and methods for 18F labeled agents |
US8410300B2 (en) * | 2006-09-21 | 2013-04-02 | Taimed Biologics, Inc. | Protease inhibitors |
US8455626B2 (en) | 2006-11-30 | 2013-06-04 | Abbott Laboratories | Aβ conformer selective anti-aβ globulomer monoclonal antibodies |
US20100311767A1 (en) | 2007-02-27 | 2010-12-09 | Abbott Gmbh & Co. Kg | Method for the treatment of amyloidoses |
EP2131865B1 (de) * | 2007-03-12 | 2014-12-17 | Nektar Therapeutics | Oligomer-proteasehemmer-konjugate |
CA2693715C (en) | 2007-07-27 | 2015-10-27 | Janssen Pharmaceutica Nv | Pyrrolopyrimidines |
EP2053033A1 (de) | 2007-10-26 | 2009-04-29 | Bayer Schering Pharma AG | Verbindungen zur Verwendung bei der Abbildung, Diagnose und/oder Behandlung von Erkrankungen des zentralen Nervensystems oder von Tumoren |
EP2100900A1 (de) | 2008-03-07 | 2009-09-16 | Universitätsspital Basel | Bombesin-analoge Peptid-antagonistische Konjugate |
JP5480824B2 (ja) | 2008-03-10 | 2014-04-23 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | Plkキナーゼ阻害剤としての4−アリール−2−アニリノ−ピリミジン |
EP2262538B1 (de) * | 2008-03-12 | 2014-12-10 | Nektar Therapeutics | Oligomer-aminosäure konjugate |
EP2116236A1 (de) | 2008-04-21 | 2009-11-11 | Université de Mons-Hainaut | Bisbenzamidinderivate als Antioxidationsmittel |
BRPI0915878A2 (pt) | 2008-07-08 | 2015-11-03 | Gilead Sciences Inc | sais ou hidratos de compostos inibidores de hiv, seu uso e composição farmacêutica que os compreende |
ES2623794T3 (es) | 2008-12-09 | 2017-07-12 | Gilead Sciences, Inc. | Intermedios para la preparación de moduladores de receptores tipo toll |
WO2010134045A1 (en) * | 2009-05-20 | 2010-11-25 | Ranbaxy Laboratories Limited | Amorphous fosamprenavir calcium |
US20120108501A1 (en) | 2009-06-12 | 2012-05-03 | Nektar Therapeutics | Protease Inhibitors |
US9085592B2 (en) | 2009-09-16 | 2015-07-21 | Ranbaxy Laboratories Limited | Process for the preparation of fosamprenavir calcium |
WO2011061590A1 (en) | 2009-11-17 | 2011-05-26 | Hetero Research Foundation | Novel carboxamide derivatives as hiv inhibitors |
WO2011061295A1 (en) | 2009-11-19 | 2011-05-26 | Blue Medical Devices Bv | Narrow profile composition-releasing expandable medical balloon catheter |
EP2507250A1 (de) | 2010-01-07 | 2012-10-10 | Pliva Hrvastka D.O.O. | Feste formen von fosamprenavir-calciumsalz und verfahren zu deren herstellung |
AU2011209788C1 (en) | 2010-01-27 | 2014-08-28 | Viiv Healthcare Company | Antiviral therapy |
US20110223131A1 (en) | 2010-02-24 | 2011-09-15 | Gilead Sciences, Inc. | Antiviral compounds |
US20110224443A1 (en) * | 2010-03-15 | 2011-09-15 | Venkata Naga Brahmeshwara Rao Mandava | Preparation of fosamprenavir calcium |
WO2011114212A1 (en) | 2010-03-19 | 2011-09-22 | Lupin Limited | Ammonium, calcium and tris salts of fosamprenavir |
JP2013523182A (ja) | 2010-04-15 | 2013-06-17 | アボット・ラボラトリーズ | アミロイドベータ結合タンパク質 |
WO2011141515A1 (en) | 2010-05-14 | 2011-11-17 | Bayer Pharma Aktiengesellschaft | Diagnostic agents for amyloid beta imaging |
WO2011158259A1 (en) | 2010-06-18 | 2011-12-22 | Matrix Laboratories Ltd | Novel process for the preparation of (3s)-tetrahydrofuran-3-yl (is, 2r)-3-[[(4-aminophenyl) sulfonyl] (isobutyl) amino]-1-benzyl-2-(phosphonooxy) propylcarbamate and its pharmaceutically acceptable salts thereof |
US8785648B1 (en) | 2010-08-10 | 2014-07-22 | The Regents Of The University Of California | PKC-epsilon inhibitors |
EP2603524A1 (de) | 2010-08-14 | 2013-06-19 | AbbVie Inc. | Amyloid-beta-bindende proteine |
US8877947B2 (en) * | 2010-09-10 | 2014-11-04 | Lupin Limited | Process for preparation of substantially pure fosamprenavir calcium and its intermediates |
GB201019043D0 (en) | 2010-11-10 | 2010-12-22 | Protea Biopharma N V | Use of 2',5'-oligoadenylate derivative compounds |
WO2012085625A1 (en) | 2010-12-21 | 2012-06-28 | Lupin Limited | Process for the preparation of fosamprenavir calcium and intermediate used in its preparation |
WO2012107937A2 (en) * | 2011-02-10 | 2012-08-16 | Mylan Laboratories Ltd | Crystalline fosamprenavir calcium and process for the preparation thereof" |
SG10201913683WA (en) | 2011-06-21 | 2020-03-30 | Alnylam Pharmaceuticals Inc | Angiopoietin-like 3 (angptl3) irna compositions and methods of use thereof |
EP3366312A1 (de) | 2011-06-23 | 2018-08-29 | Alnylam Pharmaceuticals, Inc. | Serpina 1 sirnas: materialzusammensetzungen und verfahren zur behandlung |
US9309213B2 (en) | 2011-07-11 | 2016-04-12 | Purdue Research Foundation | C-3 substituted bicyclooctane based HIV protease inhibitors |
WO2013011485A1 (en) | 2011-07-20 | 2013-01-24 | Ranbaxy Laboratories Limited | Process for the preparation of sulfonamides useful as retroviral protease inhibitors |
WO2013105118A1 (en) | 2012-01-10 | 2013-07-18 | Council Of Scientific & Industrial Research | A process for synthesis of syn azido epoxide and its use as intermediate the synthesis of amprenavir & saquinavir |
US9127274B2 (en) | 2012-04-26 | 2015-09-08 | Alnylam Pharmaceuticals, Inc. | Serpinc1 iRNA compositions and methods of use thereof |
EP2700396A3 (de) | 2012-06-20 | 2015-04-29 | Sylphar Nv | Streifen zur Abgabe einer Mundpflegezusammensetzung |
US9877981B2 (en) | 2012-10-09 | 2018-01-30 | President And Fellows Of Harvard College | NAD biosynthesis and precursors for the treatment and prevention of cancer and proliferation |
WO2014068265A1 (en) | 2012-10-29 | 2014-05-08 | Cipla Limited | Antiviral phosphonate analogues and process for preparation thereof |
PL2929031T4 (pl) | 2012-12-05 | 2022-06-27 | Alnylam Pharmaceuticals, Inc. | Kompozycje iRNA PCSK9 i sposoby ich zastosowania |
KR102605775B1 (ko) | 2013-03-14 | 2023-11-29 | 알닐람 파마슈티칼스 인코포레이티드 | 보체 성분 C5 iRNA 조성물 및 그 이용 방법 |
KR20220154244A (ko) | 2013-05-22 | 2022-11-21 | 알닐람 파마슈티칼스 인코포레이티드 | SERPINA1 iRNA 조성물 및 이의 사용 방법 |
CN110317810A (zh) | 2013-05-22 | 2019-10-11 | 阿尔尼拉姆医药品有限公司 | Tmprss6 irna组合物及其使用方法 |
AU2014362262B2 (en) | 2013-12-12 | 2021-05-13 | Alnylam Pharmaceuticals, Inc. | Complement component iRNA compositions and methods of use thereof |
KR102389968B1 (ko) | 2014-02-11 | 2022-04-25 | 알닐람 파마슈티칼스 인코포레이티드 | 케토헥소키나제(KHK) iRNA 조성물 및 그의 사용 방법 |
WO2015175510A1 (en) | 2014-05-12 | 2015-11-19 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for treating a serpinc1-associated disorder |
EA201692370A1 (ru) | 2014-05-22 | 2017-03-31 | Элнилэм Фармасьютикалз, Инк. | КОМПОЗИЦИИ иРНК АНГИОТЕНЗИНОГЕНА (AGT) И СПОСОБЫ ИХ ИСПОЛЬЗОВАНИЯ |
EP3180003B1 (de) | 2014-07-01 | 2022-01-12 | The Regents of the University of California | Pkc-epsilon-inhibitoren |
WO2016001907A1 (en) | 2014-07-02 | 2016-01-07 | Prendergast Patrick T | Mogroside iv and mogroside v as agonist/stimulator/un-blocking agent for toll-like receptor 4 and adjuvant for use in human/animal vaccine and to stimulate immunity against disease agents. |
CA2954056C (en) | 2014-07-11 | 2020-04-28 | Gilead Sciences, Inc. | Modulators of toll-like receptors for the treatment of hiv |
WO2016040589A1 (en) | 2014-09-12 | 2016-03-17 | Alnylam Pharmaceuticals, Inc. | Polynucleotide agents targeting complement component c5 and methods of use thereof |
WO2016061487A1 (en) | 2014-10-17 | 2016-04-21 | Alnylam Pharmaceuticals, Inc. | Polynucleotide agents targeting aminolevulinic acid synthase-1 (alas1) and uses thereof |
EP3212196A4 (de) | 2014-10-29 | 2018-07-11 | Wisconsin Alumni Research Foundation | Boronsäurehemmer der hiv-protease |
EP3212794B1 (de) | 2014-10-30 | 2021-04-07 | Genzyme Corporation | Polynukleotidwirkstoffe mit abzielung auf serpinc1 (at3) und verfahren zur verwendung davon |
AU2015350120B2 (en) | 2014-11-17 | 2021-05-27 | Alnylam Pharmaceuticals, Inc. | Apolipoprotein C3 (APOC3) iRNA compositions and methods of use thereof |
WO2016083490A1 (en) | 2014-11-27 | 2016-06-02 | Remynd Nv | Compounds for the treatment of amyloid-associated diseases |
JP2018510621A (ja) | 2015-02-13 | 2018-04-19 | アルナイラム ファーマシューティカルズ, インコーポレイテッドAlnylam Pharmaceuticals, Inc. | パタチン様ホスホリパーゼドメイン含有3(PNPLA3)iRNA組成物およびその使用方法 |
CN115927335A (zh) | 2015-04-13 | 2023-04-07 | 阿尔尼拉姆医药品有限公司 | 类血管生成素3(ANGPTL3)iRNA组合物及其使用方法 |
DK3288637T3 (da) | 2015-04-28 | 2022-10-17 | Newsouth Innovations Pty Ltd | Målretning af nad+ til behandling af kemoterapi- og radioterapi-induceret, kognitiv funktionsnedsættelse, neuropatier og inaktivitet |
BR112017021967A2 (pt) | 2015-05-06 | 2018-07-31 | Alnylam Pharmaceuticals Inc | composições do fator xii (fator hageman) (f12), kallikrein b, plasma (fator fletcher) 1 (klkb1), e kininogen 1 (kng1) irna e métodos de uso dos mesmos |
EP3310918B1 (de) | 2015-06-18 | 2020-08-05 | Alnylam Pharmaceuticals, Inc. | Gegen hydroxysäureoxidase (glycolat-oxidase, hao1) gerichtete polynukleotidwirkstoffe und verfahren zur verwendung davon |
EP3350328A1 (de) | 2015-09-14 | 2018-07-25 | Alnylam Pharmaceuticals, Inc. | Gegen patatin-like-phospholipasedomäne gerichtete polynukleotidmittel mit 3 (pnpla3) und verfahren zur verwendung davon |
WO2017048727A1 (en) | 2015-09-15 | 2017-03-23 | Gilead Sciences, Inc. | Modulators of toll-like recptors for the treatment of hiv |
EP4424828A1 (de) | 2015-12-07 | 2024-09-04 | Genzyme Corporation | Verfahren und zusammensetzungen zur behandlung einer serpinc1-assoziierten erkrankung |
WO2017100542A1 (en) | 2015-12-10 | 2017-06-15 | Alnylam Pharmaceuticals, Inc. | Sterol regulatory element binding protein (srebp) chaperone (scap) irna compositions and methods of use thereof |
JP2019518028A (ja) | 2016-06-10 | 2019-06-27 | アルナイラム ファーマシューティカルズ, インコーポレイテッドAlnylam Pharmaceuticals, Inc. | 補体成分C5iRNA組成物及び発作性夜間血色素尿症(PNH)を処置するためのその使用方法 |
TWI788312B (zh) | 2016-11-23 | 2023-01-01 | 美商阿尼拉製藥公司 | 絲胺酸蛋白酶抑制因子A1 iRNA組成物及其使用方法 |
SG10201913552UA (en) | 2016-12-16 | 2020-03-30 | Alnylam Pharmaceuticals Inc | Methods for treating or preventing ttr-associated diseases using transthyretin (ttr) irna compositions |
CA3060481C (en) | 2017-05-11 | 2024-04-30 | Remynd N.V. | Compounds for the treatment of epilepsy, neurodegenerative disorders and other cns disorders |
MX2020000790A (es) | 2017-07-21 | 2020-11-11 | Viiv Healthcare Co | Pautas para el tratamiento de infecciones por el vih y sida. |
EP3661937B1 (de) | 2017-08-01 | 2021-07-28 | Gilead Sciences, Inc. | Kristalline formen von ethyl ((s)-((((2r,5r)-5-(6-amino-9h-purin-9-yl)-4-fluoro-2,5-dihydrofuran-2-yl)oxy)methyl)(phenoxy)phosphoryl)-l-alaninat (gs-9131) zur behandlung von viralen infektionen |
WO2019089922A1 (en) | 2017-11-01 | 2019-05-09 | Alnylam Pharmaceuticals, Inc. | Complement component c3 irna compositions and methods of use thereof |
BR112021001613A2 (pt) | 2018-08-13 | 2021-05-04 | Alnylam Pharmaceuticals, Inc. | agentes de ácido ribonucleico de fita dupla, célula, composições farmacêuticas, métodos de inibição da expressão gênica, de inibição da replicação e de tratar um sujeito, métodos para reduzir o nível de um antígeno e para reduzir a carga viral e uso de um agente de dsrna |
KR20210116509A (ko) | 2019-01-16 | 2021-09-27 | 젠자임 코포레이션 | Serpinc1 irna 조성물 및 그의 이용 방법 |
WO2021154941A1 (en) | 2020-01-31 | 2021-08-05 | Alnylam Pharmaceuticals, Inc. | Complement component c5 irna compositions for use in the treatment of amyotrophic lateral sclerosis (als) |
CN115175909A (zh) | 2020-02-24 | 2022-10-11 | 鲁汶天主教大学 | 吡咯并吡啶和咪唑并吡啶抗病毒化合物 |
US20230218644A1 (en) | 2020-04-16 | 2023-07-13 | Som Innovation Biotech, S.A. | Compounds for use in the treatment of viral infections by respiratory syndrome-related coronavirus |
US12083099B2 (en) | 2020-10-28 | 2024-09-10 | Accencio LLC | Methods of treating symptoms of coronavirus infection with viral protease inhibitors |
WO2022136486A1 (en) | 2020-12-22 | 2022-06-30 | Luxembourg Institute Of Health (Lih) | Conolidine analogues as selective ackr3 modulators for the treatment of cancer and cardiovascular diseases |
US20240002351A1 (en) | 2021-03-04 | 2024-01-04 | Universiteit Antwerpen | Quinazolin-4-one and thieno[2,3-d]pyrimidin-4-one inhibitors of erbb4 (her4) for use in the treatment of cancer |
WO2022253785A2 (en) | 2021-05-31 | 2022-12-08 | Universität Heidelberg | Improved prostate-specific membrane antigen targeting radiopharmaceuticals and uses thereof |
WO2023021132A1 (en) | 2021-08-18 | 2023-02-23 | Katholieke Universiteit Leuven | 6-substituted- and 6,7-disubstituted-7-deazapurine ribonucleoside analogues |
WO2023046900A1 (en) | 2021-09-23 | 2023-03-30 | Katholieke Universiteit Leuven | Ribonucleoside analogues against -sars-cov-2 |
WO2023241799A1 (en) | 2022-06-15 | 2023-12-21 | Université Libre de Bruxelles | Flavanols for use in the treatment of retroviral infections |
WO2024062043A1 (en) | 2022-09-21 | 2024-03-28 | Universiteit Antwerpen | Substituted phenothiazines as ferroptosis inhibitors |
WO2024175804A1 (en) | 2023-02-24 | 2024-08-29 | Katholieke Universiteit Leuven | Nuclear transport modulators |
Family Cites Families (51)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3743722A (en) | 1971-07-14 | 1973-07-03 | Abbott Lab | Anti-coagulant isolation |
FR2459235A1 (fr) | 1979-06-14 | 1981-01-09 | Sanofi Sa | Nouveaux derives de sulfonyl-aniline, leur procede de preparation et leur application therapeutique |
JPS5946252A (ja) | 1982-09-09 | 1984-03-15 | Dainippon Ink & Chem Inc | 含フツ素アミノカルボキシレ−トおよびその製法 |
JPS5948449A (ja) | 1982-09-13 | 1984-03-19 | Dainippon Ink & Chem Inc | 直鎖状含フツ素アニオン化合物およびその製造方法 |
JPS6171830A (ja) | 1984-09-17 | 1986-04-12 | Dainippon Ink & Chem Inc | 界面活性剤組成物 |
US4616088A (en) | 1984-10-29 | 1986-10-07 | E. R. Squibb & Sons, Inc. | Amino acid ester and amide renin inhibitor |
US4629724A (en) | 1984-12-03 | 1986-12-16 | E. R. Squibb & Sons, Inc. | Amino acid ester and amide renin inhibitors |
DE3635907A1 (de) | 1986-10-22 | 1988-04-28 | Merck Patent Gmbh | Hydroxy-aminosaeurederivate |
NL8800100A (nl) | 1987-01-21 | 1988-08-16 | Sandoz Ag | Nieuwe peptidederivaten en werkwijzen voor het bereiden en toepassen van deze derivaten. |
CA1340588C (en) | 1988-06-13 | 1999-06-08 | Balraj Krishan Handa | Amino acid derivatives |
IL91780A (en) | 1988-10-04 | 1995-08-31 | Abbott Lab | History of the amine of the xenon-preventing xanine acid, the process for their preparation and the pharmaceutical preparations containing them |
WO1990007329A1 (en) | 1989-01-06 | 1990-07-12 | The Regents Of The University Of California | Selection method for pharmacologically active compounds |
US5151438A (en) | 1989-05-23 | 1992-09-29 | Abbott Laboratories | Retroviral protease inhibiting compounds |
US5354866A (en) * | 1989-05-23 | 1994-10-11 | Abbott Laboratories | Retroviral protease inhibiting compounds |
IE902295A1 (en) | 1989-07-07 | 1991-01-16 | Abbott Lab | Amino acid analog cck antagonists |
GB8927913D0 (en) * | 1989-12-11 | 1990-02-14 | Hoffmann La Roche | Amino acid derivatives |
HUT64738A (en) | 1990-06-01 | 1994-02-28 | Du Pont Merck Pharma | Process for preparing 1,4-diamino-2,3-dihydroxi-butane compounds and pharmaceutical compositions contianing them |
TW225540B (de) | 1990-06-28 | 1994-06-21 | Shionogi & Co | |
CA2096407C (en) | 1990-11-19 | 2007-10-02 | Kathryn Lea Reed | Retroviral protease inhibitors |
DE69126987T2 (de) | 1990-11-19 | 1998-03-05 | Monsanto Co | Retrovirale protease-inhibitoren |
HU9301447D0 (en) | 1990-11-19 | 1993-11-29 | Monsanto Co | Inhibitors of retrovirus protease |
WO1993023388A1 (en) | 1992-05-20 | 1993-11-25 | G.D. Searle & Co. | Method for making intermediates useful in synthesis of retroviral protease inhibitors |
ES2151618T3 (es) | 1990-11-19 | 2001-01-01 | Monsanto Co | Inhibidores de proteasas retrovirales. |
IE913840A1 (en) | 1990-11-20 | 1992-05-20 | Abbott Lab | Retroviral protease inhibiting compounds |
IL103613A (en) | 1991-11-08 | 1999-05-09 | Merck & Co Inc | VIH protease inhibitors, and the process of preparing intermediates and pharmaceutical preparations containing them. |
EP0641325B1 (de) | 1992-05-21 | 2001-03-07 | Monsanto Company | Inhibitoren retroviraler proteasen |
KR100336699B1 (ko) | 1992-08-25 | 2002-05-13 | 윌리암스 로저 에이 | 레트로바이러스 프로테아제 저해제로서 유용한히드록시에틸아미노 술폰아미드 |
RU2146668C1 (ru) | 1992-08-25 | 2000-03-20 | Джи Ди Сирл энд Компани | Сульфонилалканоиламино-гидроксиэтиламино-сульфонамидное соединение, фармацевтические композиции и способы лечения и ингибирования ретровирусных протеаз |
ATE154800T1 (de) | 1992-08-25 | 1997-07-15 | Searle & Co | N-(alkanoylamino-2-hydroxypropyl)-sulfonamide verwendbar als retrovirale proteaseninhibitoren |
HUT70475A (en) * | 1992-09-03 | 1995-10-30 | Boehringer Ingelheim Kg | New aminoacid derivates, process for producing the same and pharmaceutical compositions containing these compounds |
US5723490A (en) * | 1992-09-08 | 1998-03-03 | Vertex Pharmaceuticals Incorporated | THF-containing sulfonamide inhibitors of aspartyl protease |
IS2334B (is) | 1992-09-08 | 2008-02-15 | Vertex Pharmaceuticals Inc., (A Massachusetts Corporation) | Aspartyl próteasi hemjari af nýjum flokki súlfonamíða |
US5783701A (en) | 1992-09-08 | 1998-07-21 | Vertex Pharmaceuticals, Incorporated | Sulfonamide inhibitors of aspartyl protease |
TW372972B (en) | 1992-10-23 | 1999-11-01 | Novartis Ag | Antiretroviral acyl compounds |
CA2143191A1 (en) | 1992-10-30 | 1994-05-11 | Michael L. Vazquez | Sulfonylalkanoylamino hydroxyethylamino sulfamic acids useful as retroviral protease inhibitors |
WO1994010134A1 (en) | 1992-10-30 | 1994-05-11 | G.D. Searle & Co. | Hydroxyethylamino sulfamic acid derivatives useful as retroviral protease inhibitors |
US5484926A (en) | 1993-10-07 | 1996-01-16 | Agouron Pharmaceuticals, Inc. | HIV protease inhibitors |
AU6135294A (en) | 1993-02-12 | 1994-08-29 | Merck & Co., Inc. | Piperazine derivatives as hiv protease inhibitors |
JP3419539B2 (ja) | 1993-02-17 | 2003-06-23 | 中外製薬株式会社 | インドリン−2−オン誘導体 |
ES2127938T3 (es) | 1993-08-24 | 1999-05-01 | Searle & Co | Hidroxietilamino sulfonamidas utiles como inhibidores de proteasas retroviricas. |
IL110898A0 (en) | 1993-09-10 | 1994-11-28 | Narhex Australia Pty Ltd | Polar-substituted hydrocarbons |
IL111584A0 (en) | 1993-11-18 | 1995-01-24 | Merck & Co Inc | Prodrugs of an inhibitor of hiv protease and pharmaceutical compositions containing them |
US5527829A (en) | 1994-05-23 | 1996-06-18 | Agouron Pharmaceuticals, Inc. | HIV protease inhibitors |
DE19506742A1 (de) | 1995-02-27 | 1996-08-29 | Bayer Ag | Verwendung von Chinoxalinen in Kombination mit Protease-Inhibitoren als Arzneimittel zur Behandlung von AIDS und/oder HIV-Infektionen |
US5691372A (en) | 1995-04-19 | 1997-11-25 | Vertex Pharmaceuticals Incorporated | Oxygenated-Heterocycle containing sulfonamide inhibitors of aspartyl protease |
US5750493A (en) | 1995-08-30 | 1998-05-12 | Raymond F. Schinazi | Method to improve the biological and antiviral activity of protease inhibitors |
US5646180A (en) | 1995-12-05 | 1997-07-08 | Vertex Pharmaceuticals Incorporated | Treatment of the CNS effects of HIV |
US6180634B1 (en) | 1997-11-13 | 2001-01-30 | Merck & Co., Inc. | Combination therapy for the treatment of AIDS |
ID25551A (id) * | 1997-12-24 | 2000-10-12 | Vertex Pharma | Bahan baku obat penghambat protease aspartil |
US6436989B1 (en) * | 1997-12-24 | 2002-08-20 | Vertex Pharmaceuticals, Incorporated | Prodrugs of aspartyl protease inhibitors |
US6319946B1 (en) * | 1999-02-12 | 2001-11-20 | Vertex Pharmaceuticals Incorporated | Inhibitors of aspartyl protease |
-
1997
- 1997-12-24 US US08/998,050 patent/US6436989B1/en not_active Expired - Lifetime
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