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EE200300494A - Laiaspektrilised 2-(asendatud amino)bensoksasoolsulfoonamiidid kui HIV proteaasi inhibiitorid, nende kasutamine, farmatseutiline kompositsioon ja meetod retroviiruse replikatsiooni inhibeerimiseks - Google Patents

Laiaspektrilised 2-(asendatud amino)bensoksasoolsulfoonamiidid kui HIV proteaasi inhibiitorid, nende kasutamine, farmatseutiline kompositsioon ja meetod retroviiruse replikatsiooni inhibeerimiseks

Info

Publication number
EE200300494A
EE200300494A EEP200300494A EEP200300494A EE200300494A EE 200300494 A EE200300494 A EE 200300494A EE P200300494 A EEP200300494 A EE P200300494A EE P200300494 A EEP200300494 A EE P200300494A EE 200300494 A EE200300494 A EE 200300494A
Authority
EE
Estonia
Prior art keywords
broad
spectrum
pharmaceutical composition
substituted amino
protease inhibitors
Prior art date
Application number
EEP200300494A
Other languages
English (en)
Inventor
Louis Nestor Ghislain Surleraux Dominique
Marie Helene Vendeville Sandrine
Gaston Verschueren Wim
T.M.M.G De Bethune Marie-Pierre
Augustinus De Kock Herman
Tahri Abdellah
Erra Sol Montserrat
Original Assignee
Tibotec Pharmaceuticals Ltd.
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 Tibotec Pharmaceuticals Ltd. filed Critical Tibotec Pharmaceuticals Ltd.
Publication of EE200300494A publication Critical patent/EE200300494A/et
Publication of EE05384B1 publication Critical patent/EE05384B1/et

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/14Antivirals for RNA viruses
    • A61P31/18Antivirals for RNA viruses for HIV
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D263/00Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/52Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
    • C07D263/54Benzoxazoles; Hydrogenated benzoxazoles
    • C07D263/58Benzoxazoles; Hydrogenated benzoxazoles 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 in position 2
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic 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
    • C07D417/02Heterocyclic 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
    • C07D417/12Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic 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
    • C07D417/14Heterocyclic 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 three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D493/00Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/04Ortho-condensed systems

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Virology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • AIDS & HIV (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Plural Heterocyclic Compounds (AREA)
EEP200300494A 2001-04-09 2002-04-09 LaiaspektrilisedÁ2-(asendatudÁamino)bensoksasoolsulfoonamiididÁkuiÁHIVÁproteaasiÁinhibiitorid,ÁnendeÁkasutamine,ÁfarmatseutilineÁkompositsioonÁjaÁmeetodÁretroviiruseÁreplikatsiooniÁinhibeerimiseks EE05384B1 (et)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP01201308 2001-04-09
US28770401P 2001-05-02 2001-05-02
PCT/EP2002/004012 WO2002081478A2 (en) 2001-04-09 2002-04-09 Broadspectrum 2-(substituted-amino)-benzoxazole sulfonamide hiv protease inhibitors

Publications (2)

Publication Number Publication Date
EE200300494A true EE200300494A (et) 2003-12-15
EE05384B1 EE05384B1 (et) 2011-02-15

Family

ID=26076876

Family Applications (1)

Application Number Title Priority Date Filing Date
EEP200300494A EE05384B1 (et) 2001-04-09 2002-04-09 LaiaspektrilisedÁ2-(asendatudÁamino)bensoksasoolsulfoonamiididÁkuiÁHIVÁproteaasiÁinhibiitorid,ÁnendeÁkasutamine,ÁfarmatseutilineÁkompositsioonÁjaÁmeetodÁretroviiruseÁreplikatsiooniÁinhibeerimiseks

Country Status (25)

Country Link
US (2) US7244752B2 (et)
EP (1) EP1397367A2 (et)
JP (1) JP4417010B2 (et)
KR (1) KR100872029B1 (et)
CN (1) CN100491360C (et)
AP (1) AP1544A (et)
AR (1) AR035819A1 (et)
AU (1) AU2002257774B2 (et)
BG (1) BG66371B1 (et)
BR (1) BR0208796A (et)
CA (1) CA2442870C (et)
CZ (1) CZ303139B6 (et)
EA (1) EA007383B1 (et)
EE (1) EE05384B1 (et)
HR (1) HRP20030905B1 (et)
HU (1) HUP0303744A3 (et)
IL (1) IL158092A0 (et)
MX (1) MXPA03009179A (et)
NO (1) NO328896B1 (et)
NZ (1) NZ528954A (et)
OA (1) OA12464A (et)
PL (1) PL367084A1 (et)
SK (1) SK288232B6 (et)
WO (1) WO2002081478A2 (et)
ZA (1) ZA200307683B (et)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100491360C (zh) * 2001-04-09 2009-05-27 泰博特克药品有限公司 广谱2-(取代的-氨基)-苯并唑磺酰胺hiv蛋白酶抑制剂
EE05307B1 (et) * 2001-05-11 2010-06-15 Tibotec Pharmaceuticals Ltd. Laiaspektrilised 2-aminobensoksasoolsulfoonamiidid kui HIV proteaasi inhibiitorid, nende kasutamine, farmatseutiline kompositsioon ja meetod retroviiruse replikatsiooni inhibeerimiseks
AU2003202914A1 (en) 2002-01-07 2003-07-24 Sequoia Pharmaceuticals Broad spectrum inhibitors
US7285566B2 (en) * 2002-01-07 2007-10-23 Erickson John W Resistance-repellent retroviral protease inhibitors
US7157489B2 (en) 2002-03-12 2007-01-02 The Board Of Trustees Of The University Of Illinois HIV protease inhibitors
IL165043A0 (en) * 2002-05-17 2005-12-18 Tibotec Pharm Ltd broadspectrum substituted benzisoxazole sulfonamide hiv protease inhibitors
US7807845B2 (en) * 2004-03-11 2010-10-05 Sequoia Pharmaceuticals, Inc. Resistance-repellent retroviral protease inhibitors
CA2566340C (en) * 2004-05-07 2014-05-06 Sequoia Pharmaceuticals, Inc. Resistance-repellent retroviral protease inhibitors
PT1856125E (pt) 2005-02-25 2009-11-06 Tibotec Pharm Ltd Síntese de precursor de inibidor de proteases
DE102010044584A1 (de) * 2010-09-07 2012-03-08 Kautex Textron Gmbh & Co. Kg Kraftstoffbehälter aus thermoplastischem Kunststoff
WO2014194519A1 (en) 2013-06-07 2014-12-11 Merck Sharp & Dohme Corp. Imidazole derivatives and methods of use thereof for improving pharmacokinetics of drug

Family Cites Families (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3021326A1 (de) 1980-06-06 1981-12-17 Drägerwerk AG, 2400 Lübeck Einrichtung zur messung von mindestens zwei pneumatischen lungenparametern und messverfahren hierzu
US4448192A (en) 1982-03-05 1984-05-15 Hewlett Packard Company Medical ventilator device parametrically controlled for patient ventilation
IT1185906B (it) 1985-09-13 1987-11-18 Luciano Gattinoni Sistema ed apparecchio biomedicale per la misurazione con precisione dei valori di variazione di pressione e volume nei polmoni di un paziente
DE3919840A1 (de) 1989-06-17 1991-01-17 Hoechst Ag Verfahren zur herstellung von aromatischen sulfonsaeurechloriden
US5136043A (en) 1989-06-17 1992-08-04 Hoechst Aktiengesellschaft Process for the preparation of aromatic sulfonyl chlorides
EP0445926B1 (en) 1990-03-09 1996-08-21 Milliken Research Corporation Organic materials having sulfonamido linked poly(oxyalkylene) moieties and their preparation
US5145684A (en) 1991-01-25 1992-09-08 Sterling Drug Inc. Surface modified drug nanoparticles
PH30929A (en) 1992-09-03 1997-12-23 Janssen Pharmaceutica Nv Beads having a core coated with an antifungal and a polymer.
IS2334B (is) * 1992-09-08 2008-02-15 Vertex Pharmaceuticals Inc., (A Massachusetts Corporation) Aspartyl próteasi hemjari af nýjum flokki súlfonamíða
EP0715618B1 (en) * 1993-08-24 1998-12-16 G.D. Searle & Co. Hydroxyethylamino sulphonamides useful as retroviral protease inhibitors
PT721331E (pt) 1993-10-01 2002-05-31 Astrazeneca Ab Processo i
DK0855388T3 (da) 1993-11-23 2002-04-29 Searle & Co Fremgangsmåde til fremstilling af mellemprodukter, der kan anvendes til syntese af retrovirale proteaseinhibitorer
ATE382041T1 (de) 1995-01-20 2008-01-15 Searle Llc Bis-sulfonamid-hydroxyethylamino-derivate als inhibitoren retroviraler proteasen
US5756533A (en) * 1995-03-10 1998-05-26 G.D. Searle & Co. Amino acid hydroxyethylamino sulfonamide retroviral protease inhibitors
US5705500A (en) 1995-03-10 1998-01-06 G.D. Searle & Co. Sulfonylalkanoylamino hydroxyethylamino sulfonamide retroviral protease inhibitors
CN1530372A (zh) * 1995-03-10 2004-09-22 G.D.ɪ����˾ 杂环羰基氨基酸羟乙氨基磺酰胺逆转录病毒蛋白酶抑制剂
US6150556A (en) * 1995-03-10 2000-11-21 G. D. Dearle & Co. Bis-amino acid hydroxyethylamino sulfonamide retroviral protease inhibitors
US5691372A (en) * 1995-04-19 1997-11-25 Vertex Pharmaceuticals Incorporated Oxygenated-Heterocycle containing sulfonamide inhibitors of aspartyl protease
AU7722296A (en) * 1995-11-15 1997-06-05 G.D. Searle & Co. Substituted sulfonylalkanoylamino hydroxyethylamino sulfonamide retroviral protease inhibitors
GB9525994D0 (en) 1995-12-20 1996-02-21 Univ Manitoba Improvements in delivery of assist modes of mechanical ventilation
IL124935A (en) 1996-05-20 2001-06-14 Janssen Pharmaceutica Nv Dispersible antifungal compositions comprising itraconazole with improved bioavailability
EP0969821B1 (en) 1997-03-26 2003-06-04 Janssen Pharmaceutica N.V. Pellets having a core coated with an antifungal and a polymer
SE513969C2 (sv) 1997-05-17 2000-12-04 Draegerwerk Ag Anordning och förfarande för bestämning av respirationssystemetsmekaniska egenskaper
WO1999006254A1 (de) * 1997-07-31 1999-02-11 Continental Teves Ag & Co. Ohg Verfahren und vorrichtung zur aktivierung einer bremsanlage
AU2012199A (en) 1997-12-24 1999-07-19 Vertex Pharmaceuticals Incorporated Prodrugs of aspartyl protease inhibitors
US6436989B1 (en) 1997-12-24 2002-08-20 Vertex Pharmaceuticals, Incorporated Prodrugs of aspartyl protease inhibitors
WO1999033792A2 (en) 1997-12-24 1999-07-08 Vertex Pharmaceuticals Incorporated Prodrugs os aspartyl protease inhibitors
BR9814484A (pt) 1997-12-24 2000-10-10 Vertex Pharma "pró-drogas de inibidores de aspartil protease"
AU4828199A (en) * 1998-06-23 2000-01-10 Board Of Trustees Of The University Of Illinois, The Multi-drug resistant retroviral protease inhibitors and associated methods
CA2336160C (en) 1998-06-23 2015-02-17 The United States Of America, Represented By The Secretary, Department Of Health And Human Services Use of compounds for treating hiv
ATE398623T1 (de) * 1999-10-06 2008-07-15 Tibotec Pharm Ltd Hexahydrofuro-2,3-b furan-3-yl-n- 3-,(1,3- benzodioxol-5-ylsulfonyl)(isobutyl)amino -1- benzyl-2-hydroxypropyl carbamat als retrovirusproteasehemmer
CN100491360C (zh) * 2001-04-09 2009-05-27 泰博特克药品有限公司 广谱2-(取代的-氨基)-苯并唑磺酰胺hiv蛋白酶抑制剂

Also Published As

Publication number Publication date
US20070135447A1 (en) 2007-06-14
CA2442870A1 (en) 2002-10-17
BG108218A (bg) 2004-09-30
US20040132791A1 (en) 2004-07-08
HUP0303744A2 (hu) 2004-03-01
NO20034505L (no) 2003-12-08
NO328896B1 (no) 2010-06-07
US7595334B2 (en) 2009-09-29
HRP20030905A2 (en) 2005-08-31
AP1544A (en) 2006-01-12
SK13392003A3 (en) 2004-10-05
SK288232B6 (sk) 2014-11-04
MXPA03009179A (es) 2004-11-22
EP1397367A2 (en) 2004-03-17
HRP20030905B1 (en) 2012-03-31
CZ303139B6 (cs) 2012-04-25
CA2442870C (en) 2011-08-02
BR0208796A (pt) 2004-03-09
WO2002081478A3 (en) 2003-05-01
CN1636006A (zh) 2005-07-06
US7244752B2 (en) 2007-07-17
HUP0303744A3 (en) 2008-03-28
ZA200307683B (en) 2005-03-30
JP2004529144A (ja) 2004-09-24
EA007383B1 (ru) 2006-10-27
KR100872029B1 (ko) 2008-12-05
NO20034505D0 (no) 2003-10-08
AU2002257774B2 (en) 2007-08-30
WO2002081478A2 (en) 2002-10-17
IL158092A0 (en) 2004-03-28
KR20030090719A (ko) 2003-11-28
EA200301110A1 (ru) 2004-04-29
JP4417010B2 (ja) 2010-02-17
AR035819A1 (es) 2004-07-14
NZ528954A (en) 2005-04-29
EE05384B1 (et) 2011-02-15
AP2003002882A0 (en) 2003-12-31
OA12464A (en) 2006-05-24
PL367084A1 (en) 2005-02-21
CN100491360C (zh) 2009-05-27
CZ20032936A3 (cs) 2004-05-12
BG66371B1 (bg) 2013-10-31

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