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

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

ID=36950030

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)

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US8143421B2 (en) 2002-03-12 2012-03-27 Tibotec Pharmaceuticals Ltd. Broadspectrum substituted benzimidazole sulfonamide HIV protease inhibitors

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AU771780B2 (en) 1998-06-23 2004-04-01 Board Of Trustees Of The University Of Illinois, The Fitness assay and associated methods
CZ300031B6 (en) * 1999-10-06 2009-01-14 Tibotec Pharmaceuticals Ltd. Hexahydrofur[2,3-b]furan-3-yl-N-{3-[(1,3-benzodioxol-5-ylsulfonyl) (isobutyl)amino]-1-benzyl-2-hydroxypropyl}carbamate and pharmaceutical composition in which the carbamate is comprised
ES2275866T3 (en) 2001-02-14 2007-06-16 Tibotec Pharmaceuticals Ltd. 2- (AMINOSUSTITUDED) -BENZOTIAZOL-SULFONAMIDES OF SPACIOUS INHIBITING SPIRITS OF THE HIV PROTEASE.
AP1544A (en) * 2001-04-09 2006-01-12 Tibotec Pharm Ltd Broadspectrum 2- (substituted-amino) -benzoxazole sulfonamide HIV protease inhibitors.
EA009590B1 (en) * 2001-05-11 2008-02-28 Тиботек Фармасьютикалз Лтд. Broadspectrum 2-amino-benzoxazole sulfonamide hiv protease inhibitors
HU229505B1 (en) * 2001-09-10 2014-01-28 Tibotec Pharm Ltd Method for the preparation of hexahydro-furo[2,3-b]furan-3-ol
TWI286476B (en) * 2001-12-12 2007-09-11 Tibotec Pharm Ltd Combination of cytochrome P450 dependent protease inhibitors
JP4578101B2 (en) * 2001-12-21 2010-11-10 テイボテク・フアーマシユーチカルズ・リミテツド Heterocyclic substituted phenyl-containing sulfonamides are broad spectrum HIV protease inhibitors
US7285566B2 (en) 2002-01-07 2007-10-23 Erickson John W Resistance-repellent retroviral protease inhibitors
US7109230B2 (en) * 2002-01-07 2006-09-19 Sequoia Pharmaceuticals, Inc. 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
HUE034389T2 (en) 2002-05-16 2018-02-28 Janssen Sciences Ireland Uc Pseudopolymorphic forms of a HIV protease inhibitor
ATE371652T1 (en) 2002-05-17 2007-09-15 Tibotec Pharm Ltd SUBSTITUTED BENZISOXAZOLE SULFONAMIDE WITH BROAD-BAND HIV PROTEASE INHIBITING EFFECT
BR0305717A (en) * 2002-08-02 2004-09-28 Tibotec Pharm Ltd Broad-spectrum hiv 2-amino-benzothiazole sulfonamide protease inhibitors
JP4879484B2 (en) * 2002-08-02 2012-02-22 テイボテク・フアーマシユーチカルズ・リミテツド Broad spectrum 2-amino-benzothiazolesulfonamide HIV protease inhibitors
JP4681296B2 (en) * 2002-08-14 2011-05-11 テイボテク・フアーマシユーチカルズ・リミテツド Broad spectrum substituted oxindolesulfonamide HIV protease inhibitors
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JP2007528423A (en) 2004-03-11 2007-10-11 セコイア、ファーマシューティカルズ、インコーポレイテッド Antiviral resistance retroviral protease inhibitors
JP5073480B2 (en) 2004-05-07 2012-11-14 セコイア、ファーマシューティカルズ、インコーポレイテッド Antiviral resistance retroviral protease inhibitors
WO2006089942A1 (en) 2005-02-25 2006-08-31 Tibotec Pharmaceuticals Ltd. Protease inhibitor precursor synthesis
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TWI385173B (en) * 2005-11-28 2013-02-11 Tibotec Pharm Ltd Substituted aminophenylsulfonamide compounds as hiv protease inhibitor
TWI432438B (en) 2005-11-28 2014-04-01 Tibotec Pharm Ltd Substituted aminophenylsulfonamide compounds and derivatives as hiv protease inhibitor
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DE602007012365D1 (en) 2006-11-09 2011-03-17 Little Island Co Cork PROCESS FOR PREPARING HEXAHYDROFUROA2,3-BÜFURAN-3-OL
EP2120562A4 (en) * 2006-11-21 2010-01-13 Purdue Research Foundation Method and compositions for treating hiv infections
WO2008118849A2 (en) * 2007-03-23 2008-10-02 University Of Massachusetts Hiv-1 protease inhibitors
DE602008005012D1 (en) 2007-04-27 2011-03-31 Little Island Co Cork PREPARATION FOR N-ISOBUTYL-N- (2-HYDROXY-RIVATE
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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
WO1999067254A2 (en) 1999-12-29
AU4828199A (en) 2000-01-10

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