AR061817A1 - Inhibidores de la replicacion del virus de la hepatitis c - Google Patents

Inhibidores de la replicacion del virus de la hepatitis c

Info

Publication number
AR061817A1
AR061817A1 ARP070102987A ARP070102987A AR061817A1 AR 061817 A1 AR061817 A1 AR 061817A1 AR P070102987 A ARP070102987 A AR P070102987A AR P070102987 A ARP070102987 A AR P070102987A AR 061817 A1 AR061817 A1 AR 061817A1
Authority
AR
Argentina
Prior art keywords
group
unsubstituted
cycloalkyl
alkyl
or1a
Prior art date
Application number
ARP070102987A
Other languages
English (en)
Inventor
Scott D Seiwert
Leonid Beigelman
Lawrence M Blatt
Timothy Kercher
April L Kennedy
Original Assignee
Intermune Inc
Array Biopharma Inc
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=38752388&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=AR061817(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Intermune Inc, Array Biopharma Inc filed Critical Intermune Inc
Publication of AR061817A1 publication Critical patent/AR061817A1/es

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • 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
    • C07D403/14—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 three or more hetero 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
    • A61K31/33—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
    • A61K31/403—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 condensed with carbocyclic rings, e.g. carbazole
    • A61K31/4035—Isoindoles, e.g. phthalimide
    • 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
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
    • C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Virology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Molecular Biology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Epidemiology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

Reivindicacion 1: Un compuesto caracterizado porque responde a la formula (1): o una sal, pro-droga, o éster del mismo aceptable para uso farmacéutico, en donde: R1 y R2 son cada uno independientemente grupos sustituidos o sin sustituir que se seleccionan de H, halogeno, CN, CF3, alcoxilo C1-8, alquilo C1-8, cicloalquilo C3-7, cicloalquilalquilo C4-10, arilalquilo C7-10, o heteroarilalquilo C6-12, o R1 y R2 tomados juntos forman un anillo cicloalquilo arilo o heteroarilo C3-7, sustituido o sin sustituir; R3 y R4 son cada uno en forma independiente porciones sustituidas o no sustituidas seleccionadas del grupo formado por H, alquilo C1-8, cicloalquilo C3-7, cicloalquilalquilo C4-10, arilalquilo C7-10, y heteroarilalquilo C6-12, o R3 y R4 tomados juntos forman un anillo cicloalquílico C3-7 sustituido o no sustituido; R5 es un grupo sustituido o sin sustituir que se selecciona del grupo formado por H, alquilo C1-8, cicloalquilo C3-7, cicloalquilalquilo C4-10, arilo, arilalquilo C7-10, heteroarilo, heteroarilalquilo C6-12, -alquil C1-8-NHC(O)OR1a, - cicloalquil C3-7-NHC(O)OR1a, - cicloalquilalquil C4-10-NHC(O)OR1a, -aril- NHC(O)OR1a, -arilalquil C7-10-NHC(O)OR1a, -heteroaril-NHC(O)OR1a, y -heteroarilalquil C6-12-NHC(O)OR1a; Y tiene una formula que se selecciona del grupo formado por -C(O)NHS(O)2R1a, -C(O)NHS(O)2NR1aR1b, -C(O)C(O)NR1aR1b, C(O)C(O)OH, -C(O)NHR1a, -C(O)R1a, -C(O)OR1a, -C(O)NHC(O)R1a y -C(O)OH; en donde R1a y R1b son cada uno independientemente grupos sustituidos o sin sustituir que se seleccionan del grupo formado por H, alquilo C1-6, cicloalquilo C3-7, cicloalquilalquilo C4-10, arilo, arilalquilo C7-10, heteroarilo, y heteroarilalquilo C6-12, o NR1aR1b forma una amina secundaria alquil cíclica de tres a seis miembros sustituida o sin sustituir, o NR1aR1b en un anillo heteroarilo o heterocíclico. Reivindicacion 13: Un compuesto caracterizado porque responde a la formula (2) o una sal pro-droga, o éster del mismo aceptable para uso farmacéutico, en donde: (a) Z1 es un grupo que se configura para unirse por puente de hidrogeno a un grupo imidazol de His57 de la proteasa de NS3 y para unirse por puente de hidrogeno a un átomo de nitrogeno de Gly137 de la proteasa NS3; (b) P1' es un grupo que se configura para formar una interaccion no polar con al menos un grupo del bolsillo S1' de la proteasa NS3 que se selecciona del grupo formado por Lys136, Gly137, Ser138, His57, Gly58, Gln41, Gly42, y Phe43; (c) L es un grupo unidor que consiste en entre 1 y 5 átomos que se seleccionan del grupo formado por carbono, oxígeno, nitrogeno, hidrogeno, y azufre; (d) P2 se selecciona del grupo formado por arilo sin sustituir, arilo sustituido, heteroarilo sin sustituir, heteroarilo sustituido, heterociclo sin sustituir y heterociclo sustituido; estando P2 posicionado con L para formar una interaccion no polar con al menos un grupo del bolsillo S2 de la proteasa NS3 que se selecciona del grupo formado por His57, Arg155, Val78, Asp79, y Gln80; y (e) R5 es un grupo sustituido o sin sustituir que se selecciona del grupo formado por H, alquilo C1-8, cicloalquilo C3-7, cicloalquilalquilo C4-10, arilo, arilalquilo C7-10, heteroarilo, heteroarilalquilo C6-12, -alquil C1-8- NHC(O)OR1a, -cicloalquil C3-7-NHC(O)OR1a, -cicloalquilalquil C4-10-NHC(O)OR1a, -aril-NHC(O)OR1a, -arilalquil C7-10-NHC(O)OR1a, -heteroaril-NHC(O)OR1a, y - heteroarilalquil C6-12-NHC(O)OR1a; en donde R1a es un grupo sustituido o sin sustituir que se selecciona del grupo formado por H, alquilo C1-6, cicloalquilo C3-7, cicloalquilalquilo C4-10, arilo, arilalquilo C7-10, heteroarilo, y heteroarilalquilo C6-12. Reivindicacion 18: Un compuesto caracterizado porque responde a la formula (3) o una sal , pro-droga, o éster del mismo aceptable para uso farmacéutico, en donde: A es OH o como se muestra en formula (4); R3 y R4 son cada uno en forma independiente porciones sustituidas o no sustituidas seleccionadas del grupo formado por H, alquilo C1-8, cicloalquilo C3-7, cicloalquilalquilo C4-10, arilalquilo C7-10, y heteroalquilo C6-12, o R3 y R4 tomados juntos forman un anillo cicloalquilo C3-7 sustituido o no sustituido; R5a es un grupo sustituido o sin sustituir que se selecciona del grupo formado por H, alquilo C1-8, cicloalquilo C3-7, cicloalquilo C4-10, arilo, arilalquilo C7-10, heteroarilo, y heteroalquilo C6-12; Y tiene una formula que se selecciona del grupo formado por -C(O)NHS(O)2R1a, -C(O)NHS(O)2NR1aR1b, - C(O)C(O)NR1aR1b, -C(O)C(O)OH, C(O)NHR1a, -C(O)R1a, -C(O)OR1a, -C(O)NHC(O)R1a y -C(O)OH; en donde R1a y R1b son cada uno independientemente grupos sustituidos o sin sustituir que se seleccionan del grupo formado por H, alquilo C1-6, cicloalquilo C3- 7, cicloalquilo C4-10, arilo, arilalquilo C7-10, heteroarilo, y heteroalquilo C6-12, o NR1aR1b forma una amina secundaria alquil cíclica de tres a seis miembros sustituida o sin sustituir, o NR1aR1b es un anillo heteroarílico o heterocíclico; y Z es CH2 o tiene una formula que se selecciona del grupo formado por >NC(O)R2a, >NC(O)OR2a, >NC(O)NR2aR2b, >NS(O)2NR2aR2b, y >NR2a; en donde R2a y R2b son cada uno independientemente grupos sustituidos o sin sustituir que se seleccionan del grupo formado por H, alquilo C1-6, cicloalquilo C3-7, cicloalquilo C4-10, arilo, arilalquilo C7-10, heteroarilo, y heteroalquilo C6-12, o NR2aR2b forma una amina secundaria alquil cíclica de tres a seis miembros sustituida o sin sustituir, o NR2aR2b es un anillo heteroarilo o heterocíclico.
ARP070102987A 2006-07-05 2007-07-04 Inhibidores de la replicacion del virus de la hepatitis c AR061817A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US81891406P 2006-07-05 2006-07-05
US81912806P 2006-07-06 2006-07-06

Publications (1)

Publication Number Publication Date
AR061817A1 true AR061817A1 (es) 2008-09-24

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Application Number Title Priority Date Filing Date
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Country Status (11)

Country Link
US (2) US7781474B2 (es)
EP (1) EP2044032A2 (es)
JP (1) JP2009542690A (es)
KR (1) KR20090024834A (es)
AR (1) AR061817A1 (es)
AU (1) AU2007269606A1 (es)
CA (1) CA2657035A1 (es)
MX (1) MX2008016369A (es)
RU (1) RU2008152171A (es)
TW (1) TW200815430A (es)
WO (1) WO2008005511A2 (es)

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