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AR087051A2 - Una composicion inhibidora del virus de la hepatitis c y uso - Google Patents

Una composicion inhibidora del virus de la hepatitis c y uso

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Publication number
AR087051A2
AR087051A2 ARP120102417A ARP120102417A AR087051A2 AR 087051 A2 AR087051 A2 AR 087051A2 AR P120102417 A ARP120102417 A AR P120102417A AR P120102417 A ARP120102417 A AR P120102417A AR 087051 A2 AR087051 A2 AR 087051A2
Authority
AR
Argentina
Prior art keywords
alkyl
optionally substituted
alkoxy
cycloalkyl
amido
Prior art date
Application number
ARP120102417A
Other languages
English (en)
Inventor
Chen Yan
Allen Campbell Jeffrey
Alan Wang Xiangdong
Sun Li
Qiang-Sit Sing
Yuen-Sin Ny
Michael Scola Paul
Hewawasam Piyasena
Charles Good Andrew
Original Assignee
Bristol Myers Squibb Co
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=29584353&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=AR087051(A2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co
Publication of AR087051A2 publication Critical patent/AR087051A2/es

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/06—Tripeptides
    • 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
    • C07D498/02—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 two hetero rings
    • C07D498/04—Ortho-condensed 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/005—Enzyme inhibitors
    • 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
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • 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
    • 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
    • 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
    • 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
    • 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
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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 to ring carbon atoms
    • C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 to carbon atoms of the nitrogen-containing ring
    • C07D217/24—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic 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
    • 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
    • C07D417/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • C07K5/06052—Val-amino acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0802—Tripeptides with the first amino acid being neutral
    • C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
    • C07K5/0808—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0827—Tripeptides containing heteroatoms different from O, S, or N
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Virology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

Una composición que comprende el compuesto de la fórmula (1) en donde: (a) R¹ es alquilo C₁₋₈, cicloalquilo C₃₋₇, o alquilcicloalquilo C₄₋₁₀; (b) m es 1 ó 2; (c) n es 1 ó 2; (d) R² es H, alquilo C₁₋₆, alquenilo C₂₋₆ o cicloalquilo C₃₋₇, cada uno opcionalmente substituido con halógeno; (e) R³ es alquilo C₁₋₈ opcionalmente substituido con halo, ciano, amino, dialquilamino C₁₋₆, arilo C₆₋₁₀, alquilarilo C₇₋₁₄, alcoxi C₁₋₆, carboxi, hidroxi, ariloxi, alquilariloxi C₇₋₁₄, alquiléster C₂₋₆, alquilariléster C₈₋₁₅; alquenilo C₃₋₁₂, cicloalquilo C₃₋₇, o alquilcicloalquilo C₄₋₁₀, en donde el cicloalquilo o alquilcicloalquilo están opcionalmente sustituido con hidroxi, alquilo C₁₋₆, alquenilo C₂₋₆ o alcoxi C₁₋₆; o R³ junto con el átomo de carbono al cual se colocan, forma un grupo cicloalquilo C₃₋₇ opcionalmente substituido con alquenilo C₂₋₆; (f) Y es H, fenilo substituido con nitro, piridilo substituido con nitro, o alquilo C₁₋₆ opcionalmente substituido con ciano, OH o cicloalquilo C₃₋₇; con tal de que si R⁴ o R⁵ es H entonces Y es H; (g) B es H, alquilo C₁₋₆, R⁴-(C=O)-, R⁴O(C=O)-, R⁴-N(R⁵)-C(=O), -R⁴-N(R⁵)-C(=S)-, R⁴SO₂-, o R⁴-N(R⁵)-SO₂-; (h) R⁴ es (i) alquilo C₁₋₁₀ opcionalmente substituido con fenilo, carboxilo, alcanoilo C₁₋₆, 1 - 3 halógeno, hidroxi, -OC(O)alquilo C₁₋₆, alcoxi C₁₋₆, amino opcionalmente substituido con alquilo C₁₋₆, amido, o (alquilo inferior)amido; (ii) cicloalquilo C₃₋₇, cicloalcoxi C₃₋₇, o alquilcicloalquilo C₄₋₁₀, cada uno opcionalmente substituido con hidroxi, carboxilo, (alcoxi C₁₋₆)carbonilo, amino opcionalmente substituido con alquilo C₁₋₆, amido, o (alquilo inferior)amido; (iii) arilo C₆₋₁₀ o arilalquilo C₇₋₁₆, cada uno opcionalmente substituido con alquilo C₁₋₆, halógeno, nitro, hidroxi, amido, (alquilo inferior)amido, o amino opcionalmente substituido con alquilo C₁₋₆; (iv) Het; (v) biciclo(1.1.1)pentano; o (vi) -C(O)O-alquilo C₁₋₆, alquenilo C₂₋₆ o alquinilo C₂₋₆; (i) R⁵ es H; alquilo C₁₋₆ opcionalmente substituida con 1 - 3 halógenos; o alcoxi C₁₋₆ con tal de que R⁴ es alquilo C₁₋₁₀; (j) X es O, S, SO, SO₂, OCH₂, CH₂O o NH; (k) R es Het; o arilo C₆₋₁₀ o alquilarilo C₇₋₁₄, opcionalmente substituido con Rᵃ; y (l) Rᵃ es alquilo C₁₋₆, cicloalquilo C₃₋₇, alcoxi C₁₋₆, cicloalcoxi C₃₋₇, halo-alquilo C₁₋₆, CF₃, mono- o di-halo-alcoxi C₁₋₆, ciano, halo, tioalquilo, hidroxi, alcanoilo, NO₂, SH, amino, alquilamino C₁₋₆, dialquilamino C₁₋₆, dialquilamida C₁₋₆, carboxilo, carboxiéster C₁₋₆, alquilsulfona C₁₋₆, alquilsulfonamida C₁₋₆, dialquilo(alcoxi)amina C₁₋₆, arilo C₆₋₁₀, alquilarilo C₇₋₁₄, o un heterociclo monocíclico de 5 - 7 miembros; con la condición de que X-R no es un resto de formula (2); o una sal, solvato o profármaco farmacéuticamente aceptable del mismo y un portador farmacéuticamente aceptable. Reivindicación 2: La composición de la reivindicación 1, que comprende además un agente inmunomodulador adicional. Reivindicación 3: La composición de la reivindicación 2, en donde el agente inmunomodulador adicional se selecciona del grupo que consiste de a-, b- y d-interferones. Reivindicación 4: La composición de la reivindicación 1, que comprende además un agente antiviral. Reivindicación 5: La composición de la reivindicación 4, en donde el agente antiviral se selecciona del grupo que consiste de ribavirina y amantadina.
ARP120102417A 2002-05-20 2012-07-04 Una composicion inhibidora del virus de la hepatitis c y uso AR087051A2 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US38205502P 2002-05-20 2002-05-20

Publications (1)

Publication Number Publication Date
AR087051A2 true AR087051A2 (es) 2014-02-12

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ID=29584353

Family Applications (3)

Application Number Title Priority Date Filing Date
ARP030101746A AR040080A1 (es) 2002-05-20 2003-05-20 Inhibidores del virus de la hepatitis c
ARP120102417A AR087051A2 (es) 2002-05-20 2012-07-04 Una composicion inhibidora del virus de la hepatitis c y uso
ARP130101165A AR090649A2 (es) 2002-05-20 2013-04-11 Inhibidores del virus de la hepatitis c

Family Applications Before (1)

Application Number Title Priority Date Filing Date
ARP030101746A AR040080A1 (es) 2002-05-20 2003-05-20 Inhibidores del virus de la hepatitis c

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ARP130101165A AR090649A2 (es) 2002-05-20 2013-04-11 Inhibidores del virus de la hepatitis c

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KR (2) KR101005958B1 (es)
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WO2004101605A1 (en) * 2003-03-05 2004-11-25 Boehringer Ingelheim International Gmbh Hepatitis c inhibiting compounds
EP1599496B1 (en) * 2003-03-05 2010-11-03 Boehringer Ingelheim International GmbH Hepatitis c inhibitor peptide analogs
ATE422895T1 (de) * 2003-04-16 2009-03-15 Bristol Myers Squibb Co Makrocyclische isochinolinpeptidinhibitoren des hepatitis-c-virus
US7176208B2 (en) * 2003-04-18 2007-02-13 Enanta Pharmaceuticals, Inc. Quinoxalinyl macrocyclic hepatitis C serine protease inhibitors
EA009295B1 (ru) * 2003-05-21 2007-12-28 Бёрингер Ингельхайм Интернациональ Гмбх Соединения в качестве ингибиторов вируса гепатита с
US7273851B2 (en) 2003-06-05 2007-09-25 Enanta Pharmaceuticals, Inc. Tri-peptide hepatitis C serine protease inhibitors
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