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WO1999067254A3 - Multi-drug resistant retroviral protease inhibitors and use thereof - Google Patents

Multi-drug resistant retroviral protease inhibitors and use thereof Download PDF

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Publication number
WO1999067254A3
WO1999067254A3 PCT/US1999/014120 US9914120W WO9967254A3 WO 1999067254 A3 WO1999067254 A3 WO 1999067254A3 US 9914120 W US9914120 W US 9914120W WO 9967254 A3 WO9967254 A3 WO 9967254A3
Authority
WO
WIPO (PCT)
Prior art keywords
formula
optionally substituted
retroviral protease
resistant retroviral
multidrug
Prior art date
Application number
PCT/US1999/014120
Other languages
French (fr)
Other versions
WO1999067254A2 (en
Inventor
John W Erickson
Sergei V Gulnik
Arun K Ghosh
Khaja A Hussain
Original Assignee
Us Health
Univ Illinois
John W Erickson
Sergei V Gulnik
Arun K Ghosh
Khaja A Hussain
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 Us Health, Univ Illinois, John W Erickson, Sergei V Gulnik, Arun K Ghosh, Khaja A Hussain filed Critical Us Health
Priority to AU48281/99A priority Critical patent/AU4828199A/en
Priority to PCT/US1999/014120 priority patent/WO1999067254A2/en
Publication of WO1999067254A2 publication Critical patent/WO1999067254A2/en
Publication of WO1999067254A3 publication Critical patent/WO1999067254A3/en

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Classifications

    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4525—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • 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
    • 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
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
    • C12Q1/025—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/34—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase
    • C12Q1/37—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase involving peptidase or proteinase
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/005—Assays involving biological materials from specific organisms or of a specific nature from viruses
    • G01N2333/08—RNA viruses
    • G01N2333/15—Retroviridae, e.g. bovine leukaemia virus, feline leukaemia virus, feline leukaemia virus, human T-cell leukaemia-lymphoma virus
    • G01N2333/155—Lentiviridae, e.g. visna-maedi virus, equine infectious virus, FIV, SIV
    • G01N2333/16—HIV-1, HIV-2
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/81—Protease inhibitors
    • G01N2333/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
    • G01N2333/8142—Aspartate protease (E.C. 3.4.23) inhibitors, e.g. HIV protease inhibitors

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Wood Science & Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Zoology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Molecular Biology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Genetics & Genomics (AREA)
  • Virology (AREA)
  • Analytical Chemistry (AREA)
  • Biophysics (AREA)
  • Epidemiology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Oncology (AREA)
  • AIDS & HIV (AREA)
  • Toxicology (AREA)
  • Communicable Diseases (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

The present invention generally provides a retroviral protease-inhibiting compound represented by formula (I), or a pharmaceutically acceptable salt, a prodrug, or an ester thereof, wherein A is a group of formula (II), (III), (IV), or (V); R?1, R2, R3, R5, or R6¿ is H, or an optionally substituted and/or heteroatom-bearing alkyl, alkenyl, alkynyl, or cyclic group; Y and/or Z are CH¿2?, O, S, SO, SO2, amino, amides, carbamates, ureas or thiocarbonyl derivatives thereof, optionally substituted with an alkyl, alkenyl, or alkynyl group; n is from 1 to 5; X is a bond, an optionally substituted methylene or ethylene, an amino, O or S; Q is C(O), C(S), or SO2; m is from 0 to 6; R?4¿ is OH, =O (keto), NH¿2?, or alkylamino, including esters, amides, and salts thereof; and W is C(O), C(S), S(O), or SO2; wherein the compound inhibits a multidrug-resistant retroviral protease. Optionally, R?5 and R6¿, together the N-W bond of formula (I), comprise a 12- to 18-membered ring. Also provided are pharmaceutical compositions for, and therapeutic methods of, treating a multidrug-resistant retroviral infection in a mammal.
PCT/US1999/014120 1998-06-23 1999-06-23 Multi-drug resistant retroviral protease inhibitors and use thereof WO1999067254A2 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU48281/99A AU4828199A (en) 1998-06-23 1999-06-23 Multi-drug resistant retroviral protease inhibitors and associated methods
PCT/US1999/014120 WO1999067254A2 (en) 1998-06-23 1999-06-23 Multi-drug resistant retroviral protease inhibitors and use thereof

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US9039398P 1998-06-23 1998-06-23
US60/090,393 1998-06-23
PCT/US1999/014120 WO1999067254A2 (en) 1998-06-23 1999-06-23 Multi-drug resistant retroviral protease inhibitors and use thereof

Publications (2)

Publication Number Publication Date
WO1999067254A2 WO1999067254A2 (en) 1999-12-29
WO1999067254A3 true WO1999067254A3 (en) 2000-02-10

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1999/014120 WO1999067254A2 (en) 1998-06-23 1999-06-23 Multi-drug resistant retroviral protease inhibitors and use thereof

Country Status (2)

Country Link
AU (1) AU4828199A (en)
WO (1) WO1999067254A2 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8143421B2 (en) 2002-03-12 2012-03-27 Tibotec Pharmaceuticals Ltd. Broadspectrum substituted benzimidazole sulfonamide HIV protease inhibitors

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PT2336134T (en) 1998-06-23 2016-10-19 The Board Of Trustees Of The Univ Of Illionis Fitness assay and methods for reducing resistance of hiv to therapy
CA2386850C (en) * 1999-10-06 2010-03-30 Piet Tom Bert Paul Wigerinck Hexahydrofuro[2,3-b]furan-3-yl-n-{3-[(1,3-benzodioxol-5-ylsulfonyl)(isobutyl)amino]-1-benzyl-2-hydroxypropyl} carbamate as retroviral protease inhibitor
DK1370543T3 (en) 2001-02-14 2007-02-19 Tibotec Pharm Ltd Widespread 2- (substituted amino) benzothiazole sulfonamide HIV protease inhibitors
EP1397367A2 (en) 2001-04-09 2004-03-17 Tibotec Pharmaceuticals Ltd. Broadspectrum 2-(substituted-amino)-benzoxazole sulfonamide hiv protease inhibitors
HRP20031026B1 (en) 2001-05-11 2012-07-31 Tibotec@Pharmaceuticals@Ltd AMINO BENZOXAZOLE SULFONAMIDE INHIBITORS OF WIDE SPECTRUM HIV PROTEASE
WO2003022853A1 (en) * 2001-09-10 2003-03-20 Tibotec Pharmaceuticals Ltd. Method for the preparation of hexahydro-furo[2,3-b]furan-3-ol
AR037797A1 (en) * 2001-12-12 2004-12-01 Tibotec Pharm Ltd COMBINATION OF PROTEASA INHIBITORS DEPENDENTS OF CITOCROMO P450
CA2470964C (en) * 2001-12-21 2013-07-02 Tibotec Pharmaceuticals Ltd. Broadspectrum heterocyclic substituted phenyl containing sulfonamide hiv protease inhibitors
US7285566B2 (en) 2002-01-07 2007-10-23 Erickson John W Resistance-repellent retroviral protease inhibitors
CA2473231A1 (en) * 2002-01-07 2003-08-07 Sequoia Pharmaceuticals 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
PT1567529E (en) * 2002-05-16 2014-09-09 Janssen R & D Ireland Pseudopolymorphic forms of a hiv protease inhibitor
IL165043A0 (en) 2002-05-17 2005-12-18 Tibotec Pharm Ltd broadspectrum substituted benzisoxazole sulfonamide hiv protease inhibitors
AU2003262561B2 (en) * 2002-08-02 2008-10-16 Tibotec Pharmaceuticals Ltd. Broadspectrum 2-amino-benzothiazole sulfonamide HIV protease inhibitors
KR101327772B1 (en) * 2002-08-02 2013-11-11 얀센 알 앤드 디 아일랜드 Broadspectrum 2-amino-benzothiazole sulfonamide HIV protease inhibitors
NZ538714A (en) * 2002-08-14 2007-03-30 Tibotec Pharm Ltd Broadspectrum substituted oxindole sulfonamide HIV protease inhibitors
EP1589018A4 (en) 2002-12-27 2007-03-14 Sumitomo Chemical Co PROCESS FOR PRODUCING A DERIVATIVE OF HEXAHYDROFURANOL, INTERMEDIATE THEREOF AND PROCESS FOR PRODUCING THE SAME
GB0310593D0 (en) * 2003-05-08 2003-06-11 Leuven K U Res & Dev Peptidic prodrugs
CA2559328A1 (en) 2004-03-11 2005-09-22 Sequoia Pharmaceuticals, Inc. Resistance-repellent retroviral protease inhibitors
US7378441B2 (en) 2004-05-07 2008-05-27 Sequoia Pharmaceuticals, Inc. Resistance-repellent retroviral protease inhibitors
BRPI0607827B8 (en) 2005-02-25 2021-05-25 Janssen R & D Ireland protease inhibitor precursor compound, process for the production of said compound and its use
WO2007002172A2 (en) * 2005-06-22 2007-01-04 University Of Massachusetts Hiv-1 protease inhibitors
AR058238A1 (en) * 2005-11-28 2008-01-23 Tibotec Pharm Ltd COMPOUNDS AND DERIVATIVES OF AMINOPHENYL SULFONAMIDE REPLACED AS HIV PROTEASE INHIBITORS
AR057182A1 (en) 2005-11-28 2007-11-21 Tibotec Pharm Ltd AMINOPHENYL SULFONAMIDE COMPOUNDS REPLACED AS HIV PROTEASE INHIBITORS
US20080070910A1 (en) * 2006-07-24 2008-03-20 Desai Manoj C Therapeutic compounds and methods
AU2007316562B2 (en) 2006-11-09 2013-02-21 Janssen Sciences Ireland Unlimited Company Methods for the preparation of hexahydrofuro[2,3-b]furan-3-ol
EP2491785A1 (en) * 2006-11-21 2012-08-29 Purdue Research Foundation Method and compositions for treating HIV infections
CN101702908A (en) * 2007-03-23 2010-05-05 麻萨诸塞州大学 HIV-1 protease inhibitors
ATE498606T1 (en) 2007-04-27 2011-03-15 Tibotec Pharm Ltd PRODUCTION PROCESS FOR N-ISOBUTYL-N-(2-HYDROXY-3-AMINO-4-PHENYLBUTYL)- - NITROBENZENESULFONYLAMIDE DERIVATIVES
PA8809601A1 (en) 2007-12-24 2009-07-23 Cipla Ltd ANTI-RETROVIRAL COMBINATION
US20110046199A1 (en) 2008-01-17 2011-02-24 Purdue Research Foundation Small molecule inhibitors of hiv proteases
WO2010002994A1 (en) 2008-07-01 2010-01-07 Purdue Research Foundation Nonpeptide hiv-1 protease inhibitors
WO2010006050A1 (en) 2008-07-09 2010-01-14 Purdue Research Foundation Hiv protease inhibitors and methods for using
TWI482775B (en) * 2008-09-01 2015-05-01 Tibotec Pharm Ltd Process for the preparation of (3r,3as,6ar)-hexahydrofuro2,3-bfuran-3-yl(1s,2r)-3-(4-aminophenyl)sulfonyl(isobutyl)amino-1-benzyl-2-hydroxypropylcarbamate
US8921415B2 (en) 2009-01-29 2014-12-30 Mapi Pharma Ltd. Polymorphs of darunavir
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US5705500A (en) * 1995-03-10 1998-01-06 G.D. Searle & Co. Sulfonylalkanoylamino hydroxyethylamino sulfonamide retroviral protease inhibitors
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US5502060A (en) * 1991-10-23 1996-03-26 Merck & Co., Inc. HIV protease inhibitors
US5723490A (en) * 1992-09-08 1998-03-03 Vertex Pharmaceuticals Incorporated THF-containing sulfonamide inhibitors of aspartyl protease
WO1994014793A1 (en) * 1992-12-29 1994-07-07 G. D. Searle & Co. Cyclic sulfone containing retroviral protease inhibitors
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US5728718A (en) * 1994-12-20 1998-03-17 The United States Of America As Represented By The Department Of Health And Human Services 2,5-diamino-3,4-disubstituted-1,6-diphenylhexane isosteres comprising benzamide, sulfonamide and anthranilamide subunits and methods of using same
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8143421B2 (en) 2002-03-12 2012-03-27 Tibotec Pharmaceuticals Ltd. Broadspectrum substituted benzimidazole sulfonamide HIV protease inhibitors

Also Published As

Publication number Publication date
AU4828199A (en) 2000-01-10
WO1999067254A2 (en) 1999-12-29

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