PL3661937T3 - Formy krystaliczne ((s)-((((2r,5r)-5-(6-amino-9h-puryn-9-ylo)-4-fluoro-2,5-dihydrofuran-2-ylo)oksy)metylo)(fenoksy)fosforylo)-l-alaninianu etylu (gs-9131) do leczenia zakażeń wirusowych - Google Patents

Formy krystaliczne ((s)-((((2r,5r)-5-(6-amino-9h-puryn-9-ylo)-4-fluoro-2,5-dihydrofuran-2-ylo)oksy)metylo)(fenoksy)fosforylo)-l-alaninianu etylu (gs-9131) do leczenia zakażeń wirusowych

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Publication number
PL3661937T3
PL3661937T3 PL18755368T PL18755368T PL3661937T3 PL 3661937 T3 PL3661937 T3 PL 3661937T3 PL 18755368 T PL18755368 T PL 18755368T PL 18755368 T PL18755368 T PL 18755368T PL 3661937 T3 PL3661937 T3 PL 3661937T3
Authority
PL
Poland
Prior art keywords
alaninate
purin
dihydrofuran
phosphoryl
phenoxy
Prior art date
Application number
PL18755368T
Other languages
English (en)
Inventor
Olga Viktorovna Lapina
Bing Shi
Silas Wang
Original Assignee
Gilead Sciences, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Gilead Sciences, Inc. filed Critical Gilead Sciences, Inc.
Publication of PL3661937T3 publication Critical patent/PL3661937T3/pl

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • 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
    • C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
    • C07F9/65616—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/16—Purine radicals
    • C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5365—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines ortho- or peri-condensed with heterocyclic ring systems
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • 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
    • A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
    • A61K31/635—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
    • 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
    • A61K31/66—Phosphorus compounds
    • A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
    • C07D473/32—Nitrogen atom
    • C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D498/14—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/16—Purine radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Virology (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Engineering & Computer Science (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Communicable Diseases (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • AIDS & HIV (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
PL18755368T 2017-08-01 2018-07-30 Formy krystaliczne ((s)-((((2r,5r)-5-(6-amino-9h-puryn-9-ylo)-4-fluoro-2,5-dihydrofuran-2-ylo)oksy)metylo)(fenoksy)fosforylo)-l-alaninianu etylu (gs-9131) do leczenia zakażeń wirusowych PL3661937T3 (pl)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201762539822P 2017-08-01 2017-08-01
EP18755368.0A EP3661937B1 (en) 2017-08-01 2018-07-30 Crystalline forms of ethyl ((s)-((((2r,5r)-5-(6-amino-9h-purin-9-yl)-4-fluoro-2,5-dihydrofuran-2-yl)oxy)methyl)(phenoxy)phosphoryl)-l-alaninate (gs-9131) for treating viral infections
PCT/US2018/044415 WO2019027920A1 (en) 2017-08-01 2018-07-30 CRYSTALLINE FORMS OF ETHYL ((S) - (((((2R, 5R) -5- (6-AMINO-9H-PURIN-9-YL) -4-FLUORO-2,5-DIHYDROFURAN-2-YL) OXY ) METHYL) (PHENOXY) PHOSPHORYL) -L-ALANINATE (GS-9131) FOR THE TREATMENT OF VIRAL INFECTIONS

Publications (1)

Publication Number Publication Date
PL3661937T3 true PL3661937T3 (pl) 2021-12-20

Family

ID=63207888

Family Applications (1)

Application Number Title Priority Date Filing Date
PL18755368T PL3661937T3 (pl) 2017-08-01 2018-07-30 Formy krystaliczne ((s)-((((2r,5r)-5-(6-amino-9h-puryn-9-ylo)-4-fluoro-2,5-dihydrofuran-2-ylo)oksy)metylo)(fenoksy)fosforylo)-l-alaninianu etylu (gs-9131) do leczenia zakażeń wirusowych

Country Status (9)

Country Link
US (1) US10851125B2 (pl)
EP (2) EP3661937B1 (pl)
AR (1) AR112642A1 (pl)
ES (2) ES2892402T3 (pl)
PL (1) PL3661937T3 (pl)
PT (1) PT3661937T (pl)
SI (1) SI3661937T1 (pl)
TW (1) TW201918250A (pl)
WO (1) WO2019027920A1 (pl)

Family Cites Families (195)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB835785A (en) 1956-04-30 1960-05-25 Victor Chemical Works Method of making diaryl phosphites
MX3898E (es) 1975-12-29 1981-09-10 Monsanto Co Procedimiento mejorado para la preparacion de triesteres de n-fosfonometilglicina
US4198355A (en) 1977-03-28 1980-04-15 Mobil Oil Corporation Preparation of tertiary alkylphosphorodichloridite derivatives
US4816570A (en) 1982-11-30 1989-03-28 The Board Of Regents Of The University Of Texas System Biologically reversible phosphate and phosphonate protective groups
US4649041A (en) 1983-07-20 1987-03-10 Warner-Lambert Company Magnesium trisilicate suitable for preparation of medicament adsorbates of antinauseants
DK159431C (da) 1984-05-10 1991-03-18 Byk Gulden Lomberg Chem Fab 6-phenyl-3(2h)-pyridazinoner, fremgangsmaade til fremstilling deraf, laegemidler indeholdende disse samt anvendelse af forbindelserne til fremstilling af laegemidler
US4751221A (en) 1985-10-18 1988-06-14 Sloan-Kettering Institute For Cancer Research 2-fluoro-arabinofuranosyl purine nucleosides
US4968788A (en) 1986-04-04 1990-11-06 Board Of Regents, The University Of Texas System Biologically reversible phosphate and phosphonate protective gruops
US5455339A (en) 1986-05-01 1995-10-03 University Of Georgia Research Foundation, Inc. Method for the preparation of 2',3'-dideoxy and 2',3'-dideoxydide-hydro nucleosides
IE63869B1 (en) 1986-11-06 1995-06-14 Res Dev Foundation Aerosols containing liposomes and method for their preparation
FR2611203B1 (fr) 1987-02-20 1989-06-09 Sturtz Georges Analogues gem-diphosphoniques d'amethopterine (methotrexate) et de derives deaza-n-10 amethopterine. leur preparation et les compositions pharmaceutiques qui les contiennent
US5459256A (en) 1987-04-17 1995-10-17 The Government Of The United States Of America As Represented By The Department Of Health And Human Services Lipophilic, aminohydrolase-activated prodrugs
US5631370A (en) 1988-01-20 1997-05-20 Regents Of The University Of Minnesota Optically-active isomers of dideoxycarbocyclic nucleosides
US5466793A (en) 1988-03-01 1995-11-14 Ajinomoto Co., Inc. Process for preparing 2', 3'- dideoxyinosine
ZA894534B (en) 1988-06-20 1990-03-28 Merrell Dow Pharma Novel neplanocin derivatives
US5744600A (en) 1988-11-14 1998-04-28 Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic Phosphonomethoxy carbocyclic nucleosides and nucleotides
CA2001715C (en) 1988-11-14 1999-12-28 Muzammil M. Mansuri Carbocyclic nucleosides and nucleotides
US5202128A (en) 1989-01-06 1993-04-13 F. H. Faulding & Co. Limited Sustained release pharmaceutical composition
HU906976D0 (en) 1989-11-13 1991-05-28 Bristol Myers Squibb Co Process for producing 2', 3'-didesoxy-2'-fluoarabinonucleoside analogues
DE4003574A1 (de) 1990-02-07 1991-08-08 Bayer Ag Neue dipeptide, verfahren zu ihrer herstellung und ihre verwendung als renininhibitoren in arzneimitteln
EP0533833B1 (en) 1990-06-13 1995-12-20 GLAZIER, Arnold Phosphorous produgs
DE69116750T2 (de) 1990-07-04 1996-11-14 Merrell Dow Pharma 9-Purinyl-Phosphonsäurederivate
US5177064A (en) 1990-07-13 1993-01-05 University Of Florida Targeted drug delivery via phosphonate derivatives
EP0468119A1 (en) 1990-07-24 1992-01-29 Merrell Dow Pharmaceuticals Inc. Novel carbocyclic analogs of certain nucleosides
US5223618A (en) 1990-08-13 1993-06-29 Isis Pharmaceuticals, Inc. 4'-desmethyl nucleoside analog compounds
DE69129650T2 (de) 1990-09-14 1999-03-25 Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic, Prag/Praha Wirkstoffvorläufer von Phosphonaten
US5672697A (en) 1991-02-08 1997-09-30 Gilead Sciences, Inc. Nucleoside 5'-methylene phosphonates
DE4111730A1 (de) 1991-04-10 1992-10-15 Knoll Ag Neue cytarabin-derivate, ihre herstellung und verwendung
JP2648897B2 (ja) 1991-07-01 1997-09-03 塩野義製薬株式会社 ピリミジン誘導体
EP0531597A1 (en) 1991-09-12 1993-03-17 Merrell Dow Pharmaceuticals Inc. Novel unsaturated acyclic phosphonate derivatives of purine and pyrimidine
US5610294A (en) 1991-10-11 1997-03-11 The Du Pont Merck Pharmaceutical Company Substituted cyclic carbonyls and derivatives thereof useful as retroviral protease inhibitors
DE4138584A1 (de) 1991-11-23 1993-05-27 Hoechst Ag Carbocyclische phosphonat-nucleotidanaloge, deren herstellung und verwendung
GB9126144D0 (en) 1991-12-10 1992-02-12 British Bio Technology Compounds
FR2692265B1 (fr) 1992-05-25 1996-11-08 Centre Nat Rech Scient Composes biologiquement actifs de type phosphotriesters.
US5968942A (en) 1992-08-25 1999-10-19 G. D. Searle & Co. α- and β-amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors
IS2334B (is) 1992-09-08 2008-02-15 Vertex Pharmaceuticals Inc., (A Massachusetts Corporation) Aspartyl próteasi hemjari af nýjum flokki súlfonamíða
DE4308096A1 (de) 1993-03-13 1994-09-15 Hoechst Ag Prodrug-Derivate von Enzyminhibitoren mit Hydroxylgruppen, Verfahren zu deren Herstellung und ihre Verwendung
US5654286A (en) 1993-05-12 1997-08-05 Hostetler; Karl Y. Nucleotides for topical treatment of psoriasis, and methods for using same
CA2126601A1 (en) 1993-06-29 1994-12-30 Mitsubishi Chemical Corporation Phosphonate-nucleotide ester derivatives
JPH09500120A (ja) 1993-07-14 1997-01-07 チバ−ガイギー アクチェンゲゼルシャフト 環式ヒドラジン化合物
WO1995007920A1 (en) 1993-09-17 1995-03-23 Gilead Sciences, Inc. Nucleotide analogs
US5656745A (en) 1993-09-17 1997-08-12 Gilead Sciences, Inc. Nucleotide analogs
US5446137B1 (en) 1993-12-09 1998-10-06 Behringwerke Ag Oligonucleotides containing 4'-substituted nucleotides
US5493030A (en) 1994-02-18 1996-02-20 Syntex (U.S.A.) Inc. 5-substituted derivatives of mycophenolic acid
KR100387157B1 (ko) 1994-09-26 2003-09-29 시오노기세이야쿠가부시키가이샤 이미다졸유도체
JP2002515849A (ja) 1994-11-04 2002-05-28 ギリアード サイエンシーズ，インコーポレイテッド Ｈｉｖプロテアーゼを阻害および検出するチエパン化合物
US5543523A (en) 1994-11-15 1996-08-06 Regents Of The University Of Minnesota Method and intermediates for the synthesis of korupensamines
EP0799181A4 (en) 1994-12-23 1998-03-25 Smithkline Beecham Corp DIMERES 3.3- (DISUBSTITUTED) CYCLOHEXANE-1-CARBOXYLATE AND RELATED COMPOUNDS
ES2097703B1 (es) 1995-04-12 1997-12-01 Decox S L Una nueva composicion estimulante de la actividad cerebral basada en alcaloides de nucleo de eburnamenina, y sus metodos de preparacion.
US5747498A (en) 1996-05-28 1998-05-05 Pfizer Inc. Alkynyl and azido-substituted 4-anilinoquinazolines
AU6299496A (en) 1995-06-29 1997-01-30 Novo Nordisk A/S Novel substituted azabicyclic compounds
US5750493A (en) 1995-08-30 1998-05-12 Raymond F. Schinazi Method to improve the biological and antiviral activity of protease inhibitors
EP0852233A4 (en) 1995-09-21 1999-09-15 Nippon Shinyaku Co Ltd CYCLOSPORIN PHOSPHATE DERIVATIVES AND MEDICINAL COMPOSITION
US5914332A (en) 1995-12-13 1999-06-22 Abbott Laboratories Retroviral protease inhibiting compounds
RU2106353C1 (ru) 1996-03-19 1998-03-10 Корпорация "С энд Ти Сайенс энд Текнолоджи Инк." Соли 5'-н-фосфоната 3'- азидо-3'-дезокситимидина, являющиеся специфическими ингибиторами продукции вируса иммунодефицита человека вич-1 и вич-2
US5874577A (en) 1996-04-03 1999-02-23 Medichem Research, Inc. Method for the preparing 9-12-(Diethoxyphosphonomethoxy)ethyl!adenine and analogues thereof
US5795909A (en) 1996-05-22 1998-08-18 Neuromedica, Inc. DHA-pharmaceutical agent conjugates of taxanes
WO1998004569A1 (en) 1996-07-26 1998-02-05 Gilead Sciences, Inc. Nucleotide analogs
ES2186911T3 (es) 1996-08-13 2003-05-16 Mitsubishi Chem Corp Compuestos nucleotidico de fosfonato.
JP2002514183A (ja) 1996-09-17 2002-05-14 スーパージェン・インコーポレーテッド リン脂質薬剤誘導体
KR100560182B1 (ko) 1996-10-09 2006-03-13 파마셋 인코포레이티드 비스포스포네이트 화합물
ATE261944T1 (de) 1996-12-26 2004-04-15 Shionogi & Co Verfahren zur herstellung von carbamoylsubstituierten imidazolderivaten
US5851171A (en) 1997-11-04 1998-12-22 Advanced Cardiovascular Systems, Inc. Catheter assembly for centering a radiation source within a body lumen
WO1999029702A2 (en) 1997-12-10 1999-06-17 The Government Of The United States Of America Reppresented By The Secretary, Department Of Health And Human Services METHOD FOR SYNTHESIZING 9-(2,3-DIDEOXY-2-FLUORO-β-D-THREO-PENTOFURANOSYL)ADENINE (β-FddA)
US6436989B1 (en) 1997-12-24 2002-08-20 Vertex Pharmaceuticals, Incorporated Prodrugs of aspartyl protease inhibitors
AU2787199A (en) 1998-02-25 1999-09-15 Emory University 2'-fluoronucleosides
US6312662B1 (en) 1998-03-06 2001-11-06 Metabasis Therapeutics, Inc. Prodrugs phosphorus-containing compounds
US6174888B1 (en) 1998-05-28 2001-01-16 Novartis Ag 2-amino-7-(1-substituted-2-hydroxyethyl)-3,5-dihydropyrrolo[3,2-D]pyrimidin-4-ones
AU4125099A (en) 1998-06-01 1999-12-20 S & T Science And Technology Inc. Antiviral phosphorus derivatives of 4'-thio-5-ethyl-2'-deoxyuridine
GB9815567D0 (en) 1998-07-18 1998-09-16 Glaxo Group Ltd Antiviral compound
US6319946B1 (en) 1999-02-12 2001-11-20 Vertex Pharmaceuticals Incorporated Inhibitors of aspartyl protease
US6761903B2 (en) 1999-06-30 2004-07-13 Lipocine, Inc. Clear oil-containing pharmaceutical compositions containing a therapeutic agent
HK1043796B (en) 1999-03-05 2007-02-23 Metabasis Therapeutics, Inc. Novel phosphorus-containing prodrugs
DE19912636A1 (de) 1999-03-20 2000-09-21 Aventis Cropscience Gmbh Bicyclische Heterocyclen, Verfahren zu ihrer Herstellung und ihre Verwendung als Herbizide und pharmazeutische Mittel
US6258831B1 (en) 1999-03-31 2001-07-10 The Procter & Gamble Company Viral treatment
US6608027B1 (en) 1999-04-06 2003-08-19 Boehringer Ingelheim (Canada) Ltd Macrocyclic peptides active against the hepatitis C virus
DE19927689A1 (de) 1999-06-17 2000-12-21 Gruenenthal Gmbh Orale Darreichungsformen zur Verabreichung einer fixen Kombination von Tramadol und Diclofenac
DK1196414T3 (da) 1999-06-25 2003-11-24 Vertex Pharma Prolægemiddel af carbamathæmmer for IMPDH
US6581606B2 (en) 1999-07-06 2003-06-24 The Rx Files Corporation Method, apparatus and system for use in treating patient with a drug having an antineoplastic effect to optimize therapy and prevent an adverse drug response
EP2269654A3 (en) 1999-08-24 2011-04-13 Cellgate Inc. Enhancing drug delivery across and into epithelial tissues using oligo arginine moieties
GB9920872D0 (en) 1999-09-04 1999-11-10 Glaxo Group Ltd Benzophenones as inhibitors of reverse transcriptase
IL131887A0 (en) 1999-09-14 2001-03-19 Dpharm Ltd Phospholipid prodrugs of anti-proliferative drugs
BR0016058A (pt) 1999-12-03 2003-07-15 Univ California San Diego Compostos de fosfonato
EP1242431A1 (en) 1999-12-22 2002-09-25 Merck Frosst Canada & Co. Aromatic phosphonates as protein tyrosine phosphatase 1b (ptp-1b) inhibitors
KR20020093824A (ko) 2000-02-29 2002-12-16 미쯔비시 웰 파마 가부시키가이샤 포스포네이트 뉴클레오티드 화합물
MY164523A (en) 2000-05-23 2017-12-29 Univ Degli Studi Cagliari Methods and compositions for treating hepatitis c virus
HUP0301713A3 (en) 2000-06-13 2005-04-28 Shionogi & Co Pharmaceutical compositions containing propenone derivatives and their use
FR2810322B1 (fr) 2000-06-14 2006-11-10 Pasteur Institut PRODUCTION COMBINATOIRE D'ANALOGUES DE NUCLEOTIDES ET NUCLEOTIDES (XiTP)
UA72612C2 (en) 2000-07-06 2005-03-15 Pyrido[2.3-d]pyrimidine and pyrimido[4.5-d]pyrimidine nucleoside analogues, prodrugs and method for inhibiting growth of neoplastic cells
US6617310B2 (en) 2000-07-19 2003-09-09 Bristol-Myers Squibb Pharma Company Phosphate esters of bis-amino acid sulfonamides containing substituted benzyl amines
OA12393A (en) 2000-07-21 2006-04-18 Gilead Sciences Inc Prodrugs of phosphonate nucleotide analogues and methods for selecting and making same.
US6420586B1 (en) 2000-08-15 2002-07-16 University Of Kansas Amino acid-derived cyclic phosphonamides and methods of synthesizing the same
DE10043204A1 (de) 2000-09-01 2002-04-04 Siemens Ag Organischer Feld-Effekt-Transistor, Verfahren zur Strukturierung eines OFETs und integrierte Schaltung
ATE343384T1 (de) 2000-09-08 2006-11-15 Zeria Pharm Co Ltd Pharmazeutische zusammensetzungen enthaltend aminothiazole derivate zur behandlung von motorischen störungen des dickdarms
RU2188203C2 (ru) 2000-10-05 2002-08-27 Государственный научный центр вирусологии и биотехнологии "Вектор" 2',3'-дидегидро-2',3'-дидезокситимидин-5'[(этоксикарбонил)(этил)фосфонат]- ингибитор репродукции вируса иммунодефицита человека
GB0028429D0 (en) 2000-11-22 2001-01-10 Astrazeneca Ab Therapy
WO2002048165A2 (en) 2000-12-15 2002-06-20 Pharmasset Ltd. Antiviral agents for treatment of flaviviridae infections
MXPA03005923A (es) 2000-12-28 2004-01-26 Kissei Pharmaceuticals Co Ltd Derivados de glupopiranosiloxipirazol y su uso en medicinas.
DZ3487A1 (fr) 2001-01-22 2002-07-25 Merck Sharp & Dohme Derives de nucleoside comme inhibiteurs de l'arn polymerase virale d'arn-dependant
WO2002060893A1 (en) 2001-01-31 2002-08-08 Warner-Lambert Company Llc Method for carbamoylating alcohols
DE60221642T3 (de) 2001-02-12 2017-10-26 Wyeth LLC (n.d.Ges.d. Staates Delaware) O-desmethyl-venlafaxine succinat salz
EP1262458B1 (en) 2001-05-31 2008-03-05 Sumitomo Chemical Company, Limited Method for producing an activated alumina formed body
GB0114286D0 (en) 2001-06-12 2001-08-01 Hoffmann La Roche Nucleoside Derivatives
KR20020097384A (ko) 2001-06-20 2002-12-31 미쯔비시 도꾜 세이야꾸 가부시끼가이샤 기존의 약제에 내성변이를 가지는 바이러스에 유효한 약제
EP2305808B1 (en) 2001-06-20 2016-03-02 Nuevolution A/S Templated molecules and methods for using such molecules
JP4085233B2 (ja) 2001-06-21 2008-05-14 日本ゼオン株式会社 トナーの製造方法
DE50212935D1 (de) 2001-07-20 2008-12-04 Bioagency Ag Organo-phosphorverbindungen zur aktivierung von gamma/delta-t-zellen
DE60232981D1 (de) 2001-08-17 2009-08-27 Sankyo Agro Co Ltd 3-phenoxy-4-pyridazinolderivat und dieses enthaltende herbizide zusammensetzung
JP2005508924A (ja) 2001-08-30 2005-04-07 三菱ウェルファーマ株式会社 抗ウイルス剤
MXPA04003192A (es) 2001-11-29 2004-07-27 Pfizer Prod Inc Sales de acido succinico de 5, 7, 14-triazatetraciclo ?10.3.1.02,11.04,9? -hexadeca-2(11), 3, 5, 7, 9-pentaeno y composiciones farmacetucias de las mismas.
WO2003050129A1 (en) 2001-12-07 2003-06-19 Eli Lilly And Company Use of phosphonate nucleotide analogue for treating hepatitis b virus infections
HRP20040530A2 (en) 2001-12-12 2004-10-31 Pfizer Prod Inc Salt forms of e-2-methoxy-n-(3-(4-(3-methyl-pyridin-3-yloxy)-phenylamino)-quinazolin-6-yl)-allyl)-acetamide, its preparation and its use against cancer
UA77033C2 (uk) 2001-12-21 2006-10-16 Mgi Gp Inc Спосіб отримання водорозчинних фосфонооксиметильних похідних спирту та фенолу
US20030198666A1 (en) 2002-01-07 2003-10-23 Richat Abbas Oral insulin therapy
JP4547911B2 (ja) 2002-02-01 2010-09-22 アリアド・ファーマシューティカルズ・インコーポレイテッド リン含有化合物およびその用途
JP2005530689A (ja) 2002-02-08 2005-10-13 コンフォーマ・セラピューティクス・コーポレイション 改良された薬理学的および生物学的特性を有するアンサマイシン
US7927613B2 (en) 2002-02-15 2011-04-19 University Of South Florida Pharmaceutical co-crystal compositions
AU2003216523A1 (en) 2002-03-18 2003-10-08 Mitsubishi Pharma Corporation Treatment of pre-core hepatitis b virus mutant infections
JP2005525398A (ja) 2002-04-10 2005-08-25 オーソ−マクニール・フアーマシユーチカル・インコーポレーテツド ブラジキニン受容体モジュレーターとして有用な新規なヘテロアリールアルキルアミド誘導体
US6872827B2 (en) 2002-04-26 2005-03-29 Chembridge Research Laboratories, Inc. Somatostatin analogue compounds
US20050239054A1 (en) 2002-04-26 2005-10-27 Arimilli Murty N Method and compositions for identifying anti-HIV therapeutic compounds
WO2003090691A2 (en) 2002-04-26 2003-11-06 Gilead Sciences, Inc. Method and compositions for identifying anti-hiv therapeutic compounds
ATE541840T1 (de) 2002-09-30 2012-02-15 Gea Farmaceutisk Fabrik As Raloxifene-l-lactat oder ein hemihydrat davon, deren verwendungen, pharmazeutischen zusammensetzungen und herstellungsverfahren
AU2003290816A1 (en) 2002-11-12 2004-06-03 Pharmasset, Inc. Modified nucleosides as antiviral agents
CA2514466C (en) 2003-02-19 2015-05-26 Yale University Anti-viral nucleoside analogs and methods for treating viral infections, especially hiv infections
WO2004100960A2 (en) 2003-04-25 2004-11-25 Gilead Sciences, Inc. Anti-inflammatory phosphonate compounds
WO2004096237A2 (en) 2003-04-25 2004-11-11 Gilead Sciences, Inc. Phosphonate analogs for treating metabolic diseases
BRPI0409680A (pt) 2003-04-25 2006-04-18 Gilead Sciences Inc análogos de fosfonato anti-cáncer
US7427636B2 (en) 2003-04-25 2008-09-23 Gilead Sciences, Inc. Inosine monophosphate dehydrogenase inhibitory phosphonate compounds
JP2006524710A (ja) 2003-04-25 2006-11-02 ギリアード サイエンシーズ， インコーポレイテッド キナーゼインヒビターホスホネート抱合体
JP2010535701A (ja) 2003-04-25 2010-11-25 ギリアード サイエンシーズ， インコーポレイテッド 抗癌ホスホネートアナログ
WO2005002626A2 (en) 2003-04-25 2005-01-13 Gilead Sciences, Inc. Therapeutic phosphonate compounds
US7470724B2 (en) 2003-04-25 2008-12-30 Gilead Sciences, Inc. Phosphonate compounds having immuno-modulatory activity
US7407965B2 (en) 2003-04-25 2008-08-05 Gilead Sciences, Inc. Phosphonate analogs for treating metabolic diseases
WO2004096233A2 (en) 2003-04-25 2004-11-11 Gilead Sciences, Inc. Nucleoside phosphonate conjugates
US7432261B2 (en) 2003-04-25 2008-10-07 Gilead Sciences, Inc. Anti-inflammatory phosphonate compounds
WO2004096285A2 (en) 2003-04-25 2004-11-11 Gilead Sciences, Inc. Anti-infective phosphonate conjugates
EP1620110A2 (en) 2003-04-25 2006-02-01 Gilead Sciences, Inc. Immunomodulator phosphonate conjugates
US7452901B2 (en) 2003-04-25 2008-11-18 Gilead Sciences, Inc. Anti-cancer phosphonate analogs
CN101410120A (zh) 2003-04-25 2009-04-15 吉里德科学公司 抗炎的膦酸酯化合物
CA2523083C (en) 2003-04-25 2014-07-08 Gilead Sciences, Inc. Antiviral phosphonate analogs
EP1626950A4 (en) 2003-05-23 2007-05-23 Transform Pharmaceuticals Inc SERTRALINZUSAMMENSETZUNGEN
CN101220070B (zh) 2003-06-16 2012-07-18 味之素株式会社 肌苷及其制造方法
NZ544988A (en) 2003-07-30 2009-11-27 Gilead Sciences Inc Nucleobase phosphonate analogs for antiviral treatment
JP5144930B2 (ja) 2003-08-18 2013-02-13 ハー・ルンドベック・アクチエゼルスカベット トランス−１−（６−クロロ−３−フェニルインダン−１−イル）−３，３−ジメチルピペラジン
WO2005044279A1 (en) 2003-10-24 2005-05-19 Gilead Sciences, Inc. Purine nucleoside phosphonate conjugates
US7273717B2 (en) 2003-10-24 2007-09-25 Gilead Sciences, Inc. Methods and compositions for identifying therapeutic compounds with GS-9005 ester hydrolase B
US7432273B2 (en) 2003-10-24 2008-10-07 Gilead Sciences, Inc. Phosphonate analogs of antimetabolites
JP2007515495A (ja) 2003-12-22 2007-06-14 ギリアード サイエンシーズ， インコーポレイテッド ４’−置換カルボビル誘導体およびアバカビル誘導体ならびにｈｉｖおよびｈｃｖ抗ウイルス活性を有する関連化合物
WO2005063258A1 (en) 2003-12-22 2005-07-14 Gilead Sciences, Inc. Kinase inhibitor phosphonate conjugates
US20050171126A1 (en) 2003-12-26 2005-08-04 Ajinomoto Co., Inc. Process for the production of purine nucleoside compounds
US7404949B2 (en) 2004-03-15 2008-07-29 Unilever Home & Personal Care Usa, Division Of Conopco, Inc. Methods and compositions useful to prevent in-grown hair arising from shaving
JP2008502609A (ja) 2004-06-17 2008-01-31 オステオロジックス エイ／エス リウマチおよび関節性疾患の治療改善方法
PT1778702E (pt) 2004-07-16 2011-10-18 Gilead Sciences Inc Compostos antivirais
PL216369B1 (pl) 2004-07-27 2014-03-31 Gilead Sciences Pochodne fosfonianowe, kompozycje farmaceutyczne zawierające te pochodne oraz zastosowanie tych pochodnych do wytwarzania leku do hamowania wirusa HIV
US20060181714A1 (en) 2004-07-29 2006-08-17 Coherix, Inc Method for processing multiwavelength interferometric imaging data
US20060069060A1 (en) 2004-09-27 2006-03-30 Sanjeev Redkar Salts of decitabine
JP2006135111A (ja) 2004-11-05 2006-05-25 Canon Inc 波面収差測定装置、露光装置、及びデバイス製造方法
US7154505B2 (en) 2004-11-11 2006-12-26 Stonecube Limited Method of and apparatus for generating a representation of an object
KR20060080817A (ko) 2005-01-06 2006-07-11 씨제이 주식회사 시부트라민의 디카복실산염
MY148074A (en) 2005-05-10 2013-02-28 Novartis Ag Pharmaceutical compositions comprising imatinib and a release retardant
JP2009502964A (ja) 2005-07-27 2009-01-29 ギリアード サイエンシーズ， インコーポレイテッド Ｈｉｖを阻害するための抗ウイルス性ホスホン酸結合体
US20080279932A1 (en) 2005-08-04 2008-11-13 Jean-Louis Reber Compounds
DE102005041860A1 (de) 2005-09-02 2007-03-08 Schering Ag Nanopartikulärer Einschluss- und Ladungskomplex für pharmazeutische Formulierungen
WO2007075452A2 (en) 2005-12-16 2007-07-05 Wyeth Lyophilized compositions of a triazolopyrimidine compound
PL387008A1 (pl) 2006-03-17 2009-05-11 Invista Technologies S.A.R.L. Sposób oczyszczania triorganofosforynów przez obróbkę dodatkiem zasadowym
US20060223820A1 (en) 2006-03-21 2006-10-05 Chemagis Ltd. Crystalline aripiprazole salts and processes for preparation and purification thereof
US8895531B2 (en) 2006-03-23 2014-11-25 Rfs Pharma Llc 2′-fluoronucleoside phosphonates as antiviral agents
PT2049506E (pt) 2006-07-07 2015-10-09 Gilead Sciences Inc Moduladores de propriedades farmacocinéticas de agentes terapêuticos
WO2008100447A2 (en) 2007-02-09 2008-08-21 Gilead Sciences, Inc. Nucleoside analogs for antiviral treatment
BRPI0807581A2 (pt) 2007-02-23 2014-07-01 Gilead Science, Inc. Moduladores de propriedades farmacocinéticas de produtos terapêuticos
NZ585226A (en) 2007-11-16 2012-08-31 Gilead Sciences Inc Inhibitors of human immunodeficiency virus replication
US20090163449A1 (en) 2007-12-20 2009-06-25 Eastman Chemical Company Sulfo-polymer powder and sulfo-polymer powder blends with carriers and/or additives
JP5620376B2 (ja) 2008-07-08 2014-11-05 ギリアード サイエンシーズ， インコーポレイテッド Ｈｉｖ阻害剤化合物の塩
WO2010077613A1 (en) 2008-12-09 2010-07-08 Gilead Sciences, Inc. Modulators of toll-like receptors
US8338441B2 (en) 2009-05-15 2012-12-25 Gilead Sciences, Inc. Inhibitors of human immunodeficiency virus replication
US9790252B2 (en) 2009-07-01 2017-10-17 Cornell University 2-fluorinated riboses and arabinoses and methods of use and synthesis
EP2305680A3 (en) 2009-09-30 2011-05-18 Aurobindo Pharma Limited Novel salts of (1S,4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol
PL3290428T3 (pl) 2010-03-31 2022-02-07 Gilead Pharmasset Llc Tabletka zawierająca krystaliczny (S)-2-(((S)-(((2R,3R,4R,5R)-5-(2,4-diokso-3,4-dihydropirymidyn-1(2H)-ylo)-4-fluoro-3-hydroksy-4-metylotetrahydrofuran-2-ylo)metoksy)(fenoksy)fosforylo)amino)propanian izopropylu
US20130165489A1 (en) 2010-05-03 2013-06-27 The Trustees Of The University Of Pennsylvania Small Molecule Modulators of HIV-1 Capsid Stability and Methods Thereof
AP2013006706A0 (en) 2010-07-02 2013-02-28 Gilead Sciences Inc Napht-2-ylacetic acid derivatives to treat AIDS
SG186821A1 (en) 2010-07-02 2013-02-28 Gilead Sciences Inc 2 -quinolinyl- acetic acid derivatives as hiv antiviral compounds
SG194512A1 (en) 2011-04-21 2013-12-30 Gilead Sciences Inc Benzothiazole compounds and their pharmaceutical use
US8987437B2 (en) 2011-05-19 2015-03-24 Gilead Sciences, Inc. Processes and intermediates for preparing anti-HIV Agents
ES2553449T3 (es) 2011-07-06 2015-12-09 Gilead Sciences, Inc. Compuestos para el tratamiento de VIH
CN102863512B (zh) 2011-07-07 2016-04-20 上海泓博智源医药技术有限公司 抗病毒化合物
US9399645B2 (en) 2011-12-20 2016-07-26 Boehringer Ingelheim International Gmbh Inhibitors of HIV replication
CN105121418A (zh) 2012-04-20 2015-12-02 吉利德科学公司 苯并噻唑-6-基乙酸衍生物及其治疗hiv感染的用途
US20140094485A1 (en) 2012-10-03 2014-04-03 Gilead Sciences, Inc. Solid state forms of hiv inhibitor
WO2014055603A1 (en) 2012-10-03 2014-04-10 Gilead Sciences, Inc. Process for the preparation of an hiv integrase inhibitor
SI2822954T1 (sl) 2012-12-21 2016-07-29 Gilead Sciences, Inc. Policiklične karbamoilpiridonske spojine in njihova farmacevtska uporaba
EP2940019B1 (en) 2012-12-27 2018-03-28 Japan Tobacco Inc. SUBSTITUTED SPIROPYRIDO[1,2-a]PYRAZINE DERIVATIVE AND MEDICINAL USE THEREOF AS HIV INTEGRASE INHIBITOR
WO2015040640A2 (en) 2013-09-20 2015-03-26 Laurus Labs Private Limited An improved process for the preparation of tenofovir alafenamide or pharmaceutically acceptable salts thereof
US20180085387A1 (en) 2016-09-27 2018-03-29 Gilead Sciences, Inc. Therapeutic compositions for treatment of human immunodeficiency virus
TWI868958B (zh) 2017-01-31 2025-01-01 美商基利科學股份有限公司 替諾福韋埃拉酚胺(tenofovir alafenamide)之晶型

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