WO2013178782A1 - Inhibiteurs allostériques de la protéase ns3 du virus de l'hépatite c virus - Google Patents
Inhibiteurs allostériques de la protéase ns3 du virus de l'hépatite c virus Download PDFInfo
- Publication number
- WO2013178782A1 WO2013178782A1 PCT/EP2013/061256 EP2013061256W WO2013178782A1 WO 2013178782 A1 WO2013178782 A1 WO 2013178782A1 EP 2013061256 W EP2013061256 W EP 2013061256W WO 2013178782 A1 WO2013178782 A1 WO 2013178782A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- compound
- protease
- hepatitis
- compounds
- virus
- Prior art date
- Legal status (The legal status 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 status listed.)
- Ceased
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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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4196—1,2,4-Triazoles
-
- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
-
- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
-
- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/576—Immunoassay; Biospecific binding assay; Materials therefor for hepatitis
- G01N33/5767—Immunoassay; Biospecific binding assay; Materials therefor for hepatitis non-A, non-B hepatitis
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
- G01N2500/04—Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
Definitions
- the viral RNA is directly translated in infected cells into a precursor polyprotein which must be processed for successful viral
- the present invention also provides a method for identifying compounds that can be used according to the present invention.
- the present invention further provides a method for screening a compound capable of binding and stabilizing the Zn+2 -free NS3 protease conformation of the hepatitis C virus in a non-native inactive partially- folded conformation, wherein a compound library is subjected to a binding assay as illustrated herein in example 1 and 2 ,
- esters of the compounds of this invention include C1-C6 alkyl esters, wherein the alkyl group is a straight or branched substituted or
- prodrug refers to compounds that are rapidly
- prodrugs are provided in . Higuchi and V . Stella, "Pro-drugs as Novel Delivery Systems , " Vol . 14 of the A. C . S .
- the carrier or diluent ma- include ime delay material, such as glyceryl monoscearate or glyceryl distearate alone or with a wax, or other materials well known in the arc .
- Huh 5-2 cells were seeded at a density of 5X 103 per well in a tissue culture-treated white 96 -well view plate [Techno Plastic Products AG, Switzerland) in complete DMEM supplemented with 250 /ig/iTiL G418. After incubation for 24 hours at 37°C (5% COG ⁇ medium was removed and 2-fold serial dilutions in complete DMEM (without G418) of the test compounds were added in a total volume of 100 ⁇ .
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Analytical Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pathology (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- General Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Biochemistry (AREA)
- Oncology (AREA)
- Physics & Mathematics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP12382218 | 2012-05-30 | ||
| EP12382218.1 | 2012-05-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2013178782A1 true WO2013178782A1 (fr) | 2013-12-05 |
Family
ID=48577728
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP2013/061256 Ceased WO2013178782A1 (fr) | 2012-05-30 | 2013-05-31 | Inhibiteurs allostériques de la protéase ns3 du virus de l'hépatite c virus |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2013178782A1 (fr) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015035072A1 (fr) * | 2013-09-04 | 2015-03-12 | The Arizona Board Of Regents On Behalf Of The University Of Arizona | Traitement et/ou prévention de métastases osseuses |
| KR101771784B1 (ko) | 2015-02-17 | 2017-08-28 | 중앙대학교 산학협력단 | Tlr2 신호전달계 관련 질병의 예방 및 치료용 약학 조성물 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000032177A2 (fr) * | 1998-11-24 | 2000-06-08 | Hollis-Eden Pharmaceuticals, Inc. | Utilisation de composes 17-cetosteroides et de leurs derives, metabolites et precurseurs pour le traitement du virus de l'hepatite c ou autres togavirus |
| WO2006122156A2 (fr) * | 2005-05-09 | 2006-11-16 | Hydra Biosciences, Inc. | Composes pour moduler la fonction trpv3 |
| US20070213321A1 (en) * | 2005-05-09 | 2007-09-13 | Hydra Biosciences, Inc. | Compounds for modulating TRPV3 function |
| WO2010020676A1 (fr) * | 2008-08-20 | 2010-02-25 | Vib Vzw | Utilisation d’inhibiteurs de la topoisomérase de type i pour traiter des infections virales |
| WO2010101649A2 (fr) * | 2009-03-05 | 2010-09-10 | Pablo Gastaminza | Inhibition du récepteur sigma 1 en tant que nouvelle approche thérapeutique contre une infection par le virus de l'hépatite c |
-
2013
- 2013-05-31 WO PCT/EP2013/061256 patent/WO2013178782A1/fr not_active Ceased
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000032177A2 (fr) * | 1998-11-24 | 2000-06-08 | Hollis-Eden Pharmaceuticals, Inc. | Utilisation de composes 17-cetosteroides et de leurs derives, metabolites et precurseurs pour le traitement du virus de l'hepatite c ou autres togavirus |
| WO2006122156A2 (fr) * | 2005-05-09 | 2006-11-16 | Hydra Biosciences, Inc. | Composes pour moduler la fonction trpv3 |
| US20070213321A1 (en) * | 2005-05-09 | 2007-09-13 | Hydra Biosciences, Inc. | Compounds for modulating TRPV3 function |
| WO2010020676A1 (fr) * | 2008-08-20 | 2010-02-25 | Vib Vzw | Utilisation d’inhibiteurs de la topoisomérase de type i pour traiter des infections virales |
| WO2010101649A2 (fr) * | 2009-03-05 | 2010-09-10 | Pablo Gastaminza | Inhibition du récepteur sigma 1 en tant que nouvelle approche thérapeutique contre une infection par le virus de l'hépatite c |
Non-Patent Citations (5)
| Title |
|---|
| A. URBANI: "The Metal Binding Site of the Hepatitis C Virus NS3 Protease. A SPECTROSCOPIC INVESTIGATION", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 273, no. 30, 24 July 1998 (1998-07-24), pages 18760 - 18769, XP055076030, ISSN: 0021-9258, DOI: 10.1074/jbc.273.30.18760 * |
| DE FRANCESCO ET AL: "Advances in the development of new therapeutic agents targeting the NS3-4A serine protease or the NS5B RNA-dependent RNA polymerase of the hepatitis C virus", ADVANCED DRUG DELIVERY REVIEWS, ELSEVIER, vol. 59, no. 12, 10 October 2007 (2007-10-10), pages 1242 - 1262, XP022328021, ISSN: 0169-409X, DOI: 10.1016/J.ADDR.2007.04.016 * |
| F. ROOHVAND ET AL: "Initiation of Hepatitis C Virus Infection Requires the Dynamic Microtubule Network: ROLE OF THE VIRAL NUCLEOCAPSID PROTEIN", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 284, no. 20, 15 May 2009 (2009-05-15), pages 13778 - 13791, XP055076195, ISSN: 0021-9258, DOI: 10.1074/jbc.M807873200 * |
| OLGA ABIAN ET AL: "Conformational Stability of Hepatitis C Virus NS3 Protease", BIOPHYSICAL JOURNAL, vol. 99, no. 11, 1 December 2010 (2010-12-01), pages 3811 - 3820, XP055076078, ISSN: 0006-3495, DOI: 10.1016/j.bpj.2010.10.037 * |
| OLGA ABIAN ET AL: "Thermodynamics of zinc binding to hepatitis C virus NS3 protease: A folding by binding event", PROTEINS: STRUCTURE, FUNCTION, AND BIOINFORMATICS, vol. 77, no. 3, 15 November 2009 (2009-11-15), pages 624 - 636, XP055075941, ISSN: 0887-3585, DOI: 10.1002/prot.22475 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015035072A1 (fr) * | 2013-09-04 | 2015-03-12 | The Arizona Board Of Regents On Behalf Of The University Of Arizona | Traitement et/ou prévention de métastases osseuses |
| US10179142B2 (en) | 2013-09-04 | 2019-01-15 | The Arizona Board Of Regents On Behalf Of The University Of Arizona | Treatment and/or prevention of bone metastasis |
| KR101771784B1 (ko) | 2015-02-17 | 2017-08-28 | 중앙대학교 산학협력단 | Tlr2 신호전달계 관련 질병의 예방 및 치료용 약학 조성물 |
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