DK2873665T3 - Antivirale forbindelser - Google Patents

Antivirale forbindelser Download PDF

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Publication number
DK2873665T3
DK2873665T3 DK14175539.7T DK14175539T DK2873665T3 DK 2873665 T3 DK2873665 T3 DK 2873665T3 DK 14175539 T DK14175539 T DK 14175539T DK 2873665 T3 DK2873665 T3 DK 2873665T3
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Prior art keywords
compound
scheme
protease inhibitor
coupling
reaction
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DK14175539.7T
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English (en)
Inventor
Hongyan Guo
Darryl Kato
Thorstens A Kirschberg
Hongtae Liu
John O Link
Michael L Mitchell
Jay P Parrish
Neil Squires
Jianyu Sun
James Taylor
Elizabeth M Bacon
Eda Canales
Aesop Cho
Jeromy J Cottell
Manoj C Desai
Randall L Halcomb
Evan S Krygowski
Scott E Lazerwith
Qi Liu
Richard Mackman
Hyung-Jung Pyun
Joseph H Saugier
James D Trenkle
Winston C Tse
Randall W Vivian
Scott D Schroeder
William J Watkins
Lianhong Xu
Zheng-Yu Yang
Terry Kellar
Xiaoning Sheng
Michael O'neil Hanrahan Clarke
Chien-Hung Chou
Michael Graupe
Haolun Jin
Ryan Mcfadden
Michael R Mish
Samuel E Metobo
Barton W Phillips
Chandrasekar Venkataramani
Chuong U Kim
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Gilead Pharmasset Llc
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Publication of DK2873665T3 publication Critical patent/DK2873665T3/da

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    • 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
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    • 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
    • A61K31/4025—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 not condensed and containing further heterocyclic rings, e.g. cromakalim
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    • 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
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    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
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    • 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
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/5415—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
    • A—HUMAN NECESSITIES
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
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    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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    • 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
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    • 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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Claims (26)

  1. ANTIVIRALE FORBINDELSER
    1. Farmaceutisk sammensætning omfattende; (1) en forbindelse med formlen;
    eller et farmaceutisk acceptabelt salt deraf; (2) en NS5B-polymerasebæmmer, og (3) enNS3-proteasehæmmer.
  2. 2. Sammensætmng ifølge krav 1, hvor NS3-proteasehæmmeren er boceprevir.
  3. 3. Saminensætning ifølge krav 1, hvor NS3-proteasehæmmeren er telapievi!·,
  4. 4. Samniensætiung ifølge krav 1, hvor NS3-proteasehæmmeren er TMC435350,
  5. 5. Sammensætning ifølge krav 1, hvor NS3-proteasehæmmeren er Bl-1335.
  6. 6. Sammensæiriirig ifølge krav 1, hvor NS3-proteasehæmmeren er Bl-1230.
  7. 7. Sarnrnensæiriirig ifølge kiav 1, hvoi NS3-prøteasehæmmeren er MK-7009.
  8. 8. Sarnrnensæiriirig ifølge krav 1, hvorNS3-prøteasehæmmeren er VBY-3 76.
  9. 9. Sammensætning ifølge krav 1, hvorNS3-proteasehæmmeren er ITMN-191.
  10. 10. Sammensætning ifølge et hvilket som helst af kravene i til 9, hvor (1) er en forbindelse med formlen;
  11. 11. Farmaceutisk sammensætning omfattende; (1) en forbindelse med fomilen;
    eller et farmaceutisk acceptabelt salt deraf, (2) en NS5E-jrolymerasehæmmer, og (3) en NS3-proteasehænmier, iil anvendelse i den profylakiiske eller terapeutiske behandling af hepatitis C eller en hepatitis C associeret lidelse.
  12. 12. Sammensætning til anvendelse ifølge krav 11, hvor NSS-proteasehæmmeren er sorn defineret i et hvilket som helst af kravene 2 til 9.
  13. 13. Sainmensæin.ing til anveridelse ifølge krav 11 eller krav 12, hvor (1) er en forbindelse ined fomilen;
  14. 14. Sammensætning til anvendelse iio'lge el hvilket som .helst av kraverie 11 til 13, hvor anvendelsen er den terapeutiske behandling af hepaiitis C.
  15. 15. Forbindelse med fonnleii:
    eller et farmaceutisk acceptabelt salt deraf^ til anvendelse i kombination med en NS5B-polymerasehæiiiiiier og en lNS3-proteasehæmmer i den profylaktiske eller terapeutiske behandling af hepatitis C eller en hepatitis C associeret lidelse.
  16. 16. Forbindelse ti) anvendelse ifølge krav 15, Irvor NS3-proteasehæmrneren er som defineret i et hvilke; som helst af kravene 2 til 9.
  17. 17. Forbindelse til anvendelse ifølge krav 15 eller krav 16, hvor forbindelsen er en forbindelse med form) en;
  18. 18. Forbindelse til anvendelse ifølge et hvilket som helst af kravene 15 til 17, hvor anvendelsen er den terapeutiske behandling af hepatitis C.
  19. 19. Farmaceutisk sammensætning omfattende; (I) en forlrindelse med fonnlen;
    eller et farmaceutisk acceptabelt sal· deraf, og (2) en NS5Fl~polyrnerase]iæmmer, til anvendelse i komibination med en NS3-proteasehæmmer i den profylaktiske eller terapeutiske behandling af hepaiitis C eller en hepatitis C associere! lidelse.
  20. 20. Sairanensætning til anvendelse ifølge krav 19, hvor NS3-proteasehæiiimeren er som defineret i et hvilket som helst af kravene 2 til 9.
  21. 21. Sammensæining til anvendelse ifølge krav 19 eller krav 20, hvor (1) er en forbindelse med fonnlen;
  22. 22. Sammensætimig til anvendelse ifølge et hvilket som helst af kravene 19 til 21, hvor anvendelsen er den terapeutiske behandling af hepatitis C,
  23. 23. Kombination af {1) en forbindelse med formlen;
    eller et farmaceutisk acceptabelt salt deraf, (2) en INS.'iB-polyrnerasdiæmnier og (3) en NS3-proteasehæmmer, til anvendelse i den profyiaktiske eller terapeutiske be’nandbng af hepatitis C eller en hepatitis C associeret lidelse.
  24. 24. Kombination til anvendelse ifølge krav 23, hvor NS3 proieasehæmineren er som defineret i et hvilket som helst af kravene 2 til 9.
  25. 25. Kombination tit anvendelse ifølge krav 23 eller krav 24, Irvor {1} er en forbindelse med fornalen;
  26. 26. Kombination til anvendelse ifølge et hvilket son; iielst af kravene 23 til 25, hvor anvendelsen er den terajieiitiske behandling af hepatitis C,
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