ME01882B - 1 '-supstituisani-karba-nukleozidni prolekovi za antivirusni tretman - Google Patents

1 '-supstituisani-karba-nukleozidni prolekovi za antivirusni tretman

Info

Publication number
ME01882B
ME01882B MEP-2014-58A MEP5814A ME01882B ME 01882 B ME01882 B ME 01882B ME P5814 A MEP5814 A ME P5814A ME 01882 B ME01882 B ME 01882B
Authority
ME
Montenegro
Prior art keywords
alkyl
aryl
heterocyclyl
independently
alkynyl
Prior art date
Application number
MEP-2014-58A
Other languages
English (en)
Inventor
Aesop Cho
Choung U Kim
Adrian S Ray
Lijun Zhang
Original Assignee
Gilead Sciences 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
Application filed by Gilead Sciences Inc filed Critical Gilead Sciences Inc
Publication of ME01882B publication Critical patent/ME01882B/me

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed 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
    • 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
    • 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
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings 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
    • C07D309/10—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table

Landscapes

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

Claims (23)

1.Jedinjenje Formule I: ili njegova farmaceutski prihvatljiva so ili estar; u kojoj: R1 je H, (C1-C8)alkil, (C2-C8)alkenil, ili (C2-C8)alkinil; R2 je OH ili -0C(0)R3; svaki R3 je nezavisno H, OR4, NH(R4), N(R4)2, SR4, (C1-C8)alkil, (C2-C8)alkenil, (C2-C8)alkinil, (C3-C8)karbociklil, (C4-C8) karbociklilalkil, aril(C1-C8)alkil, heterociklil(C1-C8)alkil, aril, heterociklil ili heteroaril; svaki Ra R4 ili R6 je nezavisno (C1-C8)alkil, (C2-C8)alkenil, (C2-C8)alkinil, (C3-C8) karbociklil, (C4-C8)karbociklilalkil, aril(C1-C8)alkil, heterociklil(C1-C8)alkil, (C6-C2o)aril, (C6-C2o)heterociklil ili heteroaril; jedan od W1 ili W2 je i drugi od W1 ili W2 je OR4 ili svaki Rc, Rd ili R5 je nezavisno H, (C1-C8)alkil, (C2-C8)alkenil, (C2-C8)alkinil, (C3-C8)karbociklil, (C4-C8)karbociklilalkil, aril(C1-C8)alkil, heterociklil(C1-C8)alkil, (C6-C2o)aril, (C6-C2o)heterociklil ili heteroaril; svaki R8 je halogen, NR11R12, N(R11)OR11, NR11NR11R12, N3, NO, N02, CHO, CN, -CH(=NR11), -CH=NNHR11, -CH=N(OR11), -CH(OR11)2, -C(=0)NR11R12, -C(=S)NR11R12, -C(=0)0R11, (C1-C8)alkil, (C2-C8)alkenil, (C2-C8)alkinil, (C1-C8)karbociklilalkil, (C6-C2o)aril, (C6-C2o)heterociklil, heteroaril, -C(=0)(C1-C8)alkil, -S(0)n(C1-C8)alkil, aril(C1-C8)alkil, OR11 ili SR11; svaki n je nezavisno 0, 1, ili 2; svaki R9 ili R10 je nezavisno H, halogen, NR11R12, N(Rn)OR11, NR11NR11R12, N3, NO, N02, CHO, CN, -CH(=NR11), -CH=NHNR11, -CH=N(OR11), -CH(OR11)2, -C(=0)NR11R12, -C(=S)NR11R12, -C(=0)0R11, R11, OR11 ili SR11; svaki R11 or R12 je nezavisno H, (C1-C8)alkil, (C2-C8)alkenil, (C2-C8)alkinil, (C3-C8)karbociklil, (C4-C8)karbociklilalkil, aril(C1-C8)alkil, heterociklil(C1-C8)alkil, (C6-C2o)aril, (C2-C2o)heterociklil, heteroaril, -C(=0)(C1-C8)alkil, -S(0)n(C1-C8)alkil ili R11 i R12 zajedno sa azotom za koji su oba vezana obrazuju 3 do 7-člani heterociklični prsten gde ma koji ugljenikov atom u pomenutom heterocikličnom prstenu može opciono biti zamenjen sa -O-, -S(0)n- ili -NRa-; i gde je svaki (C1-C8)alkil, (C2-C8)alkenil, (C2-C8)alkinil, (C3-C8)karbociklil, (C4-C8)karbociklilalkil, aril(C1-C8)alkil, heterociklil(C1-C8)alkil, (C6-C2o)aril, (C6-C2o) heterociklil, heteroaril u Rc, Rd, R1, R1, R3, R4, R5, R6. R8, R11 ili R12 nezavisno, opciono supstituisan sa jednim ili više halo, hidroksi, CN, N3, N(Ra)2, NH(Ra), NH2, C(0)N(Ra)2, C(0)NH(Ra), C(0)NH2, 0C(0)N(Ra)2, 0C(0)NH(Ra), 0C(0)NH2, C(0)0Ra, 0C(0)0Ra, C(0)Ra, 0C(0)Ra, S(0)nRa. S(0)2N(Ra)2, S(0)2NH(Ra), S(0)2NH2, ORa ili Ra. ili njegova farmaceutski prihvatljiva so ili estar, gde je svaki H.
2. Jedinjenje prema zahtevu 1, predstavljeno Formulom II
3.    Jedinjenje prema zahtevu 1 ili 2, u kom je R1 (C1-C8)alkil.
4.    Jedinjenje prema ma kom od zahteva 1 -3, u kom je R2 OH.
5.    Jedinjenje prema ma kom od zahteva 1-4, predstavljeno Formulom III: ili njegova farmaceutski prihvatljiva so ili estar; u kom: R3 je (C1-C8)alkil, (C2-C8)alkenil, (C2-C8)alkinil, (C3-C8)karbociklil, (C4-C8) karbociklilalkil, aril(C1-C8)alkil, heterociklil(C1-C8)alkil, aril, heterociklil ili heteroaril; svaki Ra ili R6 je nezavisno (C1-C8)alkil, (C2-C8)alkenil, (C2-C8)alkinil, (C3-C8) karbociklil, (C4-C8)karbociklilalkil, aril(C1-C8)alkil, heterociklil(C1-C8)alkik (C6-C2o)aril, (C2-C2o)heterociklil ili heteroaril; jedan od W1 ili W2 je i drugi od W' ili or W2 je OR4 ili svaki Rc ili Rd je nezavisno H, (C1-C8)alkil, (C2-C8)alkenil, (C2-C8)alkinil, (C3-C8) karbociklil, (C4-C8)karbociklilalkil, aril(C1-C8)alkil, heterociklil(C1-C8)alkil, (C6-C2o)aril, (C6-C2o)heterociklil ili heteroaril; svaki R4 je (C6-C2o)aril ili heteroaril; svaki R8 je halogen, NR11R12, N(R11)OR11, NR11NR11Ri2, N3, -S(0)n(C1-C8)alkil, OR11 ili SR11; svaki n je nezavisno 0, 1, ili 2; svaki R9 je nezavisno H, halogen, NR11R12, N(R11)OR11, NR11NR11R12, N3, OR11 ili SR11; svaki R11 ili R12 je nezavisno H, (C1-C8)alkil, (C2-C8)alkenil, (C2-C8)alkinil, (C3-C8) karbociklil, (C4-C8)karbociklilalkil, aril(C1-C8)alkil, heterociklil(C1-C8)alkil, (C6-C2o)aril, (C2-C2o)heterociklil, heteroaril, -C(=0)(C1-C8)alkil, -S(O)n(C1-C8)alkil ili R11 i R12 zajedno sa azotom za koji su oba vezana obrazuju 3 do 7-člani heterociklični prsten u kome ma koji ugljenikov atom u pomenutom heterocikličnom prstenu može opciono biti zamenjen sa -O-, -S(0)n- ili -NRa-; i gde je svaki (C1-C8)alkil, (C2-C8)alkenil, (C2-C8)alkinil, (C3-C8)karbociklil, (C4-C8)karbociklilalkil, aril(C1-C8)alkil, heterociklil(C1-C8)alkil, (C6-C2o)aril, (C2-C2o)heterociklil, heteroaril u Rc, Rd. R3. R4, R6, R8, R11 ili R12 je, nezavisno, opciono supstituisan sa jednim ili više halo, hidroksi, CN, N3, N(Ra)2, NH(Ra), NH2, C(0)N(Ra)2, C(0)NH(Ra), C(0)NH2, OC(OjN(Ra)2, OC(OjNH(Ra), OC(OjNH2, C(OjORa, OC(O)ORa, C(0)Ra, OC(O)Ra, S(0)nRa. S(0)2N(Ra)2, S(O)2NH(Ra), S(0)2NH2, ORa ili Ra.
6. Jedinjenje prema ma kom od zahteva 1 -5, predstavljeno Formulom IV: ili njegova farmaceutski prihvatljiva so ili estar; gde: R3 je (C1-C8)alkil, (C2-C8)alkenil, (C2-C8)alkinil, (C3-C8)karbociklil ili (C4-C8) karbociklilalkil; svaki Ra je nezavisno (C1-C8)alkil, (C2-C8)alkenil, (C2-C8)alkinil, (C3-C8)karbociklil, (C4-C8)karbociklilalkil, aril(C1-C8)alkil, heterociklil(C1-C8)alkil, (C6-C2o)aril, (C2-C2o)heterociklil ili heteroaril; svaki Rc ili Rd je nezavisno H ili metil; R4 je (C6-C20)aril; R6 je (C1-C8)alkil, (C2-C8)alkenil, (C2-C8)alkinil, (C3-C8)karbociklil ili (C4-C8)karbociklilalkil; svaki R8 je halogen, NR11R12, N(R11)OR11, NRnNR11R12, N3, -S(O)n(C1-C8)alkil, OR11 ili SR11; svaki n je nezavisno 0, 1, ili 2; svaki R9 je nezavisno H, halogen, NRnR12, N(Rn)ORn, NR11NR11R12, N3, OR11 ili SR"; svaki R11 ili R12 je nezavisno H, (C1-C8)alkil, (C2-C8)alkenil, (C2-C8)alkinil, (C3-C8) karbociklil, (C4-C8)karbociklilalkil, aril(C1-C8)alkil, heterociklil(C1-C8)alkil, (C6-C2o)aril, (C2-C2o)heterociklil, heteroaril, -C(=O)(C1-C8)alkil, -S(0)n(C1-C8)alkil ili R11 i R12 zajedno sa azotom za koji su oba vezana obrazuju 3 do 7-člani heterociklični prsten gde ma koji ugljenikov atom iz navedenog heterocikličnog prstena može opciono biti zamenjen sa -O-, -S(0)n- ili -NRa-; i gde je svaki (C1-C8)alkil, (C2-C8)alkenil, (C2-C8)alkinil, (C3-C8)karbociklil, (C4-C8)karbociklilalkil, aril(C1-C8)alkil, heterociklil(C1-C8)alkil, (C6-C2o)aril, (C2-C20) heterociklil, heteroaril u R3, R4. R6, R8, R11 ili R12 je, nezavisno, opciono supstituisan sa jednim ili više halo, hidroksi, CN, N3, N(Ra)2, NH(Ra), NH2, C(0)N(Ra)2, C(0)NH(Ra), C(0)NH2, 0C(0)N(Ra)2, 0C(0)NH(Ra), 0C(0)NH2, C(0)0Ra, 0C(0)0Ra, C(0)Ra, 0C(0)Ra, S(0)nRa. S(0)2N(Ra)2, S(0)2NH(Ra), S(0)2NH2, ORa ili Ra.
7.    Jedinjenje prema ma    kom od     zahteva    1 -6, u kom je hiralnost na fosforu     R.
8.    Jedinjenje prema ma    kom od     zahteva    1-6, u kom je hiralnost na fosforu     S.
9.    Jedinjenje prema ma    kom od     zahteva    1-8, u kom je R3 (C1-C8)alkil.
10.    Jedinjenje prema ma kom od zahteva 1-9, u kom je jedan od Rc ili Rd H i drugi od Rc ili Rd je (C1-C8)alkil.
11.    Jedinjenje prema ma kom od zahteva 1-10, u kom je R6 (C1-C8)alkil.
12.    Jedinjenje prema ma kom od zahteva 1-11, u kom je R8 NR11 R12 ili OR11.
13.    Jedinjenje prema ma    kom od    zahteva    1-12, u kom je R4 H ili NR11 R12.
14.    Jedinjenje prema ma    kom od    zahteva    1-13, u kom je svaki R11 i R12 H.
15.    Jedinjenje prema ma    kom od     zahteva    1-14, u kom je R8 NH2 a R9 je H.
16.    Jedinjenje prema ma    kom od     zahteva    1-15, u kom je R4 (C6-C2o)aril.
17.    Jedinjenje prema zahtevu 1, koje je: ili njegova farmaceutski prihvatljiva so ili estar.
18.    Farmaceutska smeša koja sadrži terapeutski efektivnu količinu jedinjenja ili njegove farmaceutski prihvatljive soli ili estra, prema ma kom od zahteva 1-17 i farmaceutski prihvatljiv nosač.
19.    Farmaceutska smeša prema zahtevu 18, koja dalje sadrži najmanje jedan dodatni terapeutski agens, odabran iz grupe koja se sastoji od: interferona, ribavirina ili njihovih analoga, inhibitora HCV NS3 proteaze, NS5a inhibitora, inhibitora alfa-glukozidaze 1, hepatoprotektanata, antagonista mevalonat dekarboksilaze, antagonista sistema renin-angiotenzin, drugih anti-fibrotskih sredstava, nukleozidnih ili nukleotidnih inhibitora HCV NS5B polimeraze, ne-nukleozidnih inhibitora HCV NS5B polimeraze, HCV NS5A inhibitora, TLR-7 agonista, ciklofdinskih inhibitora, HCV IRES inhibitora, farmakokinetskih inhejsera i drugih lekova za lečenje HCV-a.
20.    Jedinjenje, prema ma kom od zahteva 1 do 17, za upotrebu u inhibisanju HCV polimeraze, koje podrazumeva primenjivanje sisaru kome je to neophodno terapeutski efektivne količine jedinjenja ili njegove farmaceutski prihvatljive soli ili estra, prema ma kom od zahteva 1-17.
21.    Jedinjenje, prema ma kom od zahteva 1 do 17, ili farmaceutska smeša prema zahtevu 18 ili zahtevu 19, za upotrebu u lečenju virusne infekcije prouzrokovane hepatitis C virusom, gde tretman podrazumeva primenjivanje sisaru kome je to neophodno terapeutski efektivne količine jedinjenja ili njegove farmaceutski prihvatljive soli ili estra, prema ma kom od zahteva 1 do 17, ili farmaceutske smeše prema zahtevu 18 ili zahtevu 19.
22.    Jedinjenje ili smeša za korišćenje u lečenju virusne infekcije prouzrokovane hepatitis C virusom, prema zahtevu 21, koja dalje uključuje primenjivanje najmanje jednog dodatnog terapeutskog sredstva, odabranog iz grupe koja se sastoji od: interferona, ribavirina ili njihovih analoga, inhibitora HCV NS3 proteaze, NS5a inhibitora, inhibitora alfa-glukozidaze 1, hepatoprotektanata, antagonista mevalonat dekarboksilaze, antagonista sistema renin-angiotenzin. drugih anti-fibrotskih sredstava, nukleozidnih ili nukleotidnih inhibitora HCV NS5B polimeraze, ne-nukleozidnih inhibitora HCV NS5B polimeraze, HCV NS5A inhibitora, TLR-7 agonista, ciklofilinskih inhibitora, HCV IRES inhibitora, farmakokinetskih inhejsera i drugih lekova za lečenje HCV-a.
23.    Jedinjenje prema ma kom od zahteva 1 do 17, ili farmaceutska smeša prema zahtevu 18 ili zahtevu 19, za upotrebu u terapiji.
MEP-2014-58A 2010-05-28 2011-05-26 1 '-supstituisani-karba-nukleozidni prolekovi za antivirusni tretman ME01882B (me)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US34959710P 2010-05-28 2010-05-28
US35335110P 2010-06-10 2010-06-10
US36604110P 2010-07-20 2010-07-20
EP11725838.4A EP2576534B1 (en) 2010-05-28 2011-05-26 1'-substituted-carba-nucleoside prodrugs for antiviral treatment
PCT/US2011/038253 WO2011150288A1 (en) 2010-05-28 2011-05-26 1'-substituted-carba-nucleoside prodrugs for antiviral treatment
US13/117,060 US8415308B2 (en) 2010-05-28 2011-05-26 1′-substituted-carba-nucleoside prodrugs for antiviral treatment

Publications (1)

Publication Number Publication Date
ME01882B true ME01882B (me) 2014-12-20

Family

ID=45375840

Family Applications (1)

Application Number Title Priority Date Filing Date
MEP-2014-58A ME01882B (me) 2010-05-28 2011-05-26 1 '-supstituisani-karba-nukleozidni prolekovi za antivirusni tretman

Country Status (17)

Country Link
US (1) US8415308B2 (me)
EP (1) EP2576534B1 (me)
JP (4) JP5837577B2 (me)
AR (1) AR084389A1 (me)
CY (1) CY1115479T1 (me)
DK (1) DK2576534T3 (me)
ES (1) ES2465265T3 (me)
HR (1) HRP20140370T1 (me)
ME (1) ME01882B (me)
PL (1) PL2576534T3 (me)
PT (1) PT2576534E (me)
RS (1) RS53244B (me)
SI (1) SI2576534T1 (me)
SM (1) SMT201400048B (me)
TW (1) TW201201815A (me)
UY (1) UY33414A (me)
WO (1) WO2011150288A1 (me)

Families Citing this family (77)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MY164523A (en) 2000-05-23 2017-12-29 Univ Degli Studi Cagliari Methods and compositions for treating hepatitis c virus
US7824851B2 (en) 2002-11-15 2010-11-02 Idenix Pharmaceuticals, Inc. 2′-branched nucleosides and Flaviviridae mutation
AU2009240630B2 (en) 2008-04-23 2013-07-18 Gilead Sciences, Inc. Carba-nucleoside analogs for antiviral treatment
TWI483950B (zh) 2009-09-21 2015-05-11 Gilead Sciences Inc 用於製備１’－取代碳核苷類似物之方法及中間物
TW201201815A (en) * 2010-05-28 2012-01-16 Gilead Sciences Inc 1'-substituted-carba-nucleoside prodrugs for antiviral treatment
WO2012012465A1 (en) 2010-07-19 2012-01-26 Clarke, Michael, O'neil Hanrahan Methods for the preparation of diasteromerically pure phosphoramidate prodrugs
PH12013500035A1 (en) 2010-07-22 2013-03-11 Gilead Sciences Inc Methods and compounds for treating paramyxoviridae virus infections
WO2012087596A1 (en) * 2010-12-20 2012-06-28 Gilead Sciences, Inc. Combinations for treating hcv
EP2691409B1 (en) 2011-03-31 2018-02-21 Idenix Pharmaceuticals LLC. Compounds and pharmaceutical compositions for the treatment of viral infections
AR088441A1 (es) 2011-09-12 2014-06-11 Idenix Pharmaceuticals Inc Compuestos de carboniloximetilfosforamidato sustituido y composiciones farmaceuticas para el tratamiento de infecciones virales
AU2012308295B2 (en) 2011-09-16 2017-10-26 Gilead Sciences, Inc. Methods for treating HCV
EP2768838A1 (en) 2011-10-14 2014-08-27 IDENIX Pharmaceuticals, Inc. Substituted 3',5'-cyclic phosphates of purine nucleotide compounds and pharmaceutical compositions for the treatment of viral infections
WO2013177195A1 (en) 2012-05-22 2013-11-28 Idenix Pharmaceuticals, Inc. 3',5'-cyclic phosphate prodrugs for hcv infection
US9109001B2 (en) 2012-05-22 2015-08-18 Idenix Pharmaceuticals, Inc. 3′,5′-cyclic phosphoramidate prodrugs for HCV infection
GEP20176800B (en) * 2012-05-22 2018-01-10 Idenix Pharmaceuticals Llk D-amino acid compounds for liver disease
WO2013174962A1 (en) 2012-05-25 2013-11-28 Janssen R&D Ireland Uracyl spirooxetane nucleosides
EP2900682A1 (en) 2012-09-27 2015-08-05 IDENIX Pharmaceuticals, Inc. Esters and malonates of sate prodrugs
CN111848711A (zh) 2012-10-08 2020-10-30 埃迪尼克斯医药有限责任公司 用于hcv感染的2′-氯核苷类似物
EP2909210A4 (en) 2012-10-17 2016-04-06 Merck Sharp & Dohme 2'-DISUBSTITUTED NUCLEOSIDE DERIVATIVES AND METHOD FOR THE USE THEREOF FOR THE TREATMENT OF VIRUS DISEASES
EP2909209B1 (en) 2012-10-17 2022-08-03 Merck Sharp & Dohme LLC 2'-cyano substituted nucleoside derivatives and methods of use thereof for treatment of viral diseases
US10723754B2 (en) 2012-10-22 2020-07-28 Idenix Pharmaceuticals Llc 2′,4′-bridged nucleosides for HCV infection
US9211300B2 (en) 2012-12-19 2015-12-15 Idenix Pharmaceuticals Llc 4′-fluoro nucleosides for the treatment of HCV
MY172166A (en) 2013-01-31 2019-11-15 Gilead Pharmasset Llc Combination formulation of two antiviral compounds
US9339541B2 (en) 2013-03-04 2016-05-17 Merck Sharp & Dohme Corp. Thiophosphate nucleosides for the treatment of HCV
EP2970358B1 (en) 2013-03-04 2021-06-30 Idenix Pharmaceuticals LLC 3'-deoxy nucleosides for the treatment of hcv
US20140271547A1 (en) 2013-03-13 2014-09-18 Idenix Pharmaceuticals, Inc. Amino acid phosphoramidate pronucleotides of 2'-cyano, azido and amino nucleosides for the treatment of hcv
US9187515B2 (en) 2013-04-01 2015-11-17 Idenix Pharmaceuticals Llc 2′,4′-fluoro nucleosides for the treatment of HCV
WO2014197578A1 (en) 2013-06-05 2014-12-11 Idenix Pharmaceuticals, Inc. 1',4'-thio nucleosides for the treatment of hcv
EP3027636B1 (en) 2013-08-01 2022-01-05 Idenix Pharmaceuticals LLC D-amino acid phosphoramidate pronucleotides of halogeno pyrimidine compounds for liver disease
UA119050C2 (uk) 2013-11-11 2019-04-25 Ґілеад Саєнсиз, Інк. ПІРОЛО[1.2-f][1.2.4]ТРИАЗИНИ, ЯКІ ВИКОРИСТОВУЮТЬСЯ ДЛЯ ЛІКУВАННЯ РЕСПІРАТОРНО-СИНЦИТІАЛЬНИХ ВІРУСНИХ ІНФЕКЦІЙ
WO2015161137A1 (en) 2014-04-16 2015-10-22 Idenix Pharmaceuticals, Inc. 3'-substituted methyl or alkynyl nucleosides for the treatment of hcv
US9856263B2 (en) 2014-04-28 2018-01-02 Pfizer Inc. Heteroaromatic compounds and their use as dopamine D1 ligands
TWI678369B (zh) 2014-07-28 2019-12-01 美商基利科學股份有限公司 用於治療呼吸道合胞病毒感染之噻吩並［３,２-ｄ］嘧啶、呋喃並［３,２-ｄ］嘧啶及吡咯並［３,２-ｄ］嘧啶化合物類
TWI673283B (zh) 2014-08-21 2019-10-01 美商基利科學股份有限公司 ２’－氯胺基嘧啶酮及嘧啶二酮核苷類
TWI740546B (zh) 2014-10-29 2021-09-21 美商基利科學股份有限公司 製備核糖苷的方法
SG10202105371YA (en) 2014-12-26 2021-07-29 Univ Emory N4-hydroxycytidine and derivatives and anti-viral uses related thereto
GEAP202215528A (en) 2015-03-06 2022-11-10 Atea Pharmaceuticals Inc B-D-2'-DEOXY-2'a-FLUORO-2'-B-C-SUBSTITUTED-2-MODIFIED-N6-SUBSTITUTED PURINE NUCLEOTIDES FOR HCV TREATMENT
CN107709344B (zh) 2015-05-01 2022-07-15 共晶制药股份有限公司 用于治疗黄病毒科病毒和癌症的核苷类似物
AU2016302005B2 (en) 2015-08-05 2021-03-04 Metro International Biotech, Llc Nicotinamide mononucleotide derivatives and their uses
SG10202109869XA (en) * 2015-09-16 2021-10-28 Gilead Sciences Inc Methods for treating arenaviridae and coronaviridae virus infections
AU2017241524B2 (en) 2016-03-28 2021-07-08 Incyte Corporation Pyrrolotriazine compounds as TAM inhibitors
US10202412B2 (en) 2016-07-08 2019-02-12 Atea Pharmaceuticals, Inc. β-D-2′-deoxy-2′-substituted-4′-substituted-2-substituted-N6-substituted-6-aminopurinenucleotides for the treatment of paramyxovirus and orthomyxovirus infections
LU100724B1 (en) 2016-07-14 2018-07-31 Atea Pharmaceuticals Inc Beta-d-2'-deoxy-2'-alpha-fluoro-2'-beta-c-substituted-4'-fluoro-n6-substituted-6-amino-2-substituted purine nucleotides for the treatment of hepatitis c virus infection
BR112019004297A2 (pt) 2016-09-07 2019-05-28 Atea Pharmaceuticals Inc método, uso de uma quantidade eficaz de um composto, composto, e, composição farmacêutica.
US20190350960A1 (en) 2017-01-04 2019-11-21 President And Fellows Of Harvard College Modulating nudix homology domain (nhd) with nicotinamide mononucleotide analogs and derivatives of same
SG11201906163TA (en) 2017-02-01 2019-08-27 Atea Pharmaceuticals Inc Nucleotide hemi-sulfate salt for the treatment of hepatitis c virus
CN110869028B (zh) 2017-03-14 2023-01-20 吉利德科学公司 治疗猫冠状病毒感染的方法
ES2938859T3 (es) * 2017-05-01 2023-04-17 Gilead Sciences Inc Una forma cristalina de (S)-2-etilbutilo 2-(((S)-(((2R,3S,4R,5R)-5-(4-aminopirrolo[2,1-f][1,2,4]triazin-7-il)-5-ciano-3,4-dihidroxitetrahidrofuran-2-il)metoxi)(fenoxi)fosforil)amino)propanoato
WO2019014247A1 (en) 2017-07-11 2019-01-17 Gilead Sciences, Inc. COMPOSITIONS COMPRISING POLYMERASE RNA INHIBITOR AND CYCLODEXTRIN FOR THE TREATMENT OF VIRAL INFECTIONS
FI3706762T3 (fi) 2017-12-07 2024-12-13 Univ Emory N4-hydroksisytidiini ja johdannaisia sekä niihin liittyviä virusten vastaisia käyttötapoja
EP3773753A4 (en) 2018-04-10 2021-12-22 ATEA Pharmaceuticals, Inc. TREATMENT OF PATIENTS INFECTED WITH THE HEPATITIS C VIRUS WITH CIRRHOSIS
CN118662520A (zh) 2020-01-27 2024-09-20 吉利德科学公司 用于治疗SARS CoV-2感染的方法
CN113214262B (zh) * 2020-02-05 2023-07-07 华创合成制药股份有限公司 一种含有胍基的化合物及其制备方法和用途
CN111320662B (zh) * 2020-02-17 2022-11-25 南京医科大学 一类n-苄基取代的二脒那秦衍生物及其药物用途
TWI884403B (zh) * 2020-02-18 2025-05-21 美商基利科學股份有限公司 抗病毒化合物
EP4106876B1 (en) 2020-02-18 2025-09-17 Gilead Sciences, Inc. Antiviral compounds
TWI794742B (zh) 2020-02-18 2023-03-01 美商基利科學股份有限公司 抗病毒化合物
TWI874791B (zh) 2020-02-18 2025-03-01 美商基利科學股份有限公司 抗病毒化合物
US10874687B1 (en) 2020-02-27 2020-12-29 Atea Pharmaceuticals, Inc. Highly active compounds against COVID-19
US11613553B2 (en) 2020-03-12 2023-03-28 Gilead Sciences, Inc. Methods of preparing 1′-cyano nucleosides
CN121401286A (zh) * 2020-03-22 2026-01-27 盈擘生技股份有限公司 用于预防或暴露后治疗感染或呼吸疾病的抗病毒组合物及其用途
EP4132651B1 (en) 2020-04-06 2026-03-18 Gilead Sciences, Inc. Inhalation formulations of 1'-cyano substituted carbanucleoside analogs
CN112778310B (zh) * 2020-04-20 2025-05-30 中国科学院上海药物研究所 核苷类似物或含有核苷类似物的组合制剂在抗病毒中的应用
US20230173077A1 (en) * 2020-04-30 2023-06-08 AJK Biopharmaceutical, LLC Fatty acyl and fatty ether conjugates of remdesivir and its active metabolites as antivirals
ES3041698T3 (en) 2020-05-29 2025-11-13 Gilead Sciences Inc Remdesivir for the treatment of viral infections
EP4172160A2 (en) 2020-06-24 2023-05-03 Gilead Sciences, Inc. 1'-cyano nucleoside analogs and uses thereof
EP4200301B1 (en) 2020-08-24 2025-02-26 Gilead Sciences, Inc. Phospholipid compounds and uses thereof
HUE067491T2 (hu) 2020-08-27 2024-10-28 Gilead Sciences Inc Vegyületek és eljárások vírusfertõzések kezelésére
CR20230160A (es) 2020-10-08 2023-06-02 Merck Sharp & Dohme Llc Preparación de derivados de oxindol como nuevos inhibidores de la diacilglicerol o-aciltransferasa 2
TWI811812B (zh) 2020-10-16 2023-08-11 美商基利科學股份有限公司 磷脂化合物及其用途
US12558364B2 (en) 2021-01-20 2026-02-24 Regents Of The University Of Minnesota Next generation remdesivir antivirals
WO2022166581A1 (zh) * 2021-02-07 2022-08-11 石家庄迪斯凯威医药科技有限公司 一种核苷酸衍生物及其药物组合物和用途
KR102923359B1 (ko) 2021-04-16 2026-02-05 길리애드 사이언시즈, 인코포레이티드 아미드를 사용한 카르바뉴클레오시드를 제조하는 방법
JP2024525164A (ja) 2021-06-17 2024-07-10 アテア ファーマシューティカルズ， インコーポレイテッド 有利な抗ｈｃｖ併用療法
EP4387977A1 (en) 2021-08-18 2024-06-26 Gilead Sciences, Inc. Phospholipid compounds and methods of making and using the same
AU2023227794A1 (en) 2022-03-02 2024-10-17 Gilead Sciences, Inc. Compounds and methods for treatment of viral infections
US12357577B1 (en) 2024-02-02 2025-07-15 Gilead Sciences, Inc. Pharmaceutical formulations and uses thereof

Family Cites Families (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19912636A1 (de) 1999-03-20 2000-09-21 Aventis Cropscience Gmbh Bicyclische Heterocyclen, Verfahren zu ihrer Herstellung und ihre Verwendung als Herbizide und pharmazeutische Mittel
US6566365B1 (en) 1999-11-04 2003-05-20 Biochem Pharma Inc. Method for the treatment of Flaviviridea viral infection using nucleoside analogues
JP2003523978A (ja) 2000-02-18 2003-08-12 シャイアー・バイオケム・インコーポレイテッド ヌクレオシドアナログを用いるｆｌａｖｉｖｉｒｕｓ感染の処置もしくは予防するための方法
MY164523A (en) 2000-05-23 2017-12-29 Univ Degli Studi Cagliari Methods and compositions for treating hepatitis c virus
US20030008841A1 (en) 2000-08-30 2003-01-09 Rene Devos Anti-HCV nucleoside derivatives
ATE491459T1 (de) 2000-10-18 2011-01-15 Pharmasset Inc Modifizierte nukleoside zur behandlung von virusinfektionen und abnormaler zellulärer proliferation
DZ3487A1 (fr) 2001-01-22 2002-07-25 Merck Sharp & Dohme Derives de nucleoside comme inhibiteurs de l'arn polymerase virale d'arn-dependant
US20040006002A1 (en) 2001-09-28 2004-01-08 Jean-Pierre Sommadossi Methods and compositions for treating flaviviruses and pestiviruses using 4'-modified nucleoside
WO2003100009A2 (en) 2002-05-23 2003-12-04 Biocryst Pharmaceuticals, Inc. Enhancing the efficacy of reverse transcriptase and dna polymerase inhibitors (nucleoside analogs) using pnp inhibitors and/or 2'-deoxyguanosine and/or prodrug thereof
US7824851B2 (en) 2002-11-15 2010-11-02 Idenix Pharmaceuticals, Inc. 2′-branched nucleosides and Flaviviridae mutation
US7534767B2 (en) * 2004-06-15 2009-05-19 Merck & Co., Inc. C-purine nucleoside analogs as inhibitors of RNA-dependent RNA viral polymerase
WO2006121820A1 (en) 2005-05-05 2006-11-16 Valeant Research & Development Phosphoramidate prodrugs for treatment of viral infection
CN101287472B (zh) * 2005-08-15 2011-10-12 弗·哈夫曼-拉罗切有限公司 抗病毒的4'-取代前核苷酸的氨基磷酸酯类化合物
JP5116687B2 (ja) 2005-11-02 2013-01-09 バイエル・ファルマ・アクチェンゲゼルシャフト がんおよび他の過剰増殖性疾患の処置のためのピロロ［２，１−ｆ］［１，２，４］トリアジン−４−イルアミンＩＧＦ−１Ｒキナーゼ阻害剤
US7842672B2 (en) * 2006-07-07 2010-11-30 Gilead Sciences, Inc. Phosphonate inhibitors of HCV
SG177974A1 (en) 2007-01-12 2012-02-28 Biocryst Pharm Inc Antiviral nucleoside analogs
WO2008141079A1 (en) * 2007-05-10 2008-11-20 Biocryst Pharmaceuticals, Inc. Tetrahydrofuro [3 4-d] dioxolane compounds for use in the treatment of viral infections and cancer
TW200942243A (en) 2008-03-05 2009-10-16 Biocryst Pharm Inc Antiviral therapeutic agents
AU2009240630B2 (en) 2008-04-23 2013-07-18 Gilead Sciences, Inc. Carba-nucleoside analogs for antiviral treatment
AR072428A1 (es) * 2008-07-01 2010-08-25 Medivir Ab Derivados de pirimidin nucleotidos inhibidores de polimerasas del virus de la hepatitis c (vhc), composiciones farmaceuticas que los contienen y metodo para prepararlos.
EP2313102A2 (en) 2008-07-03 2011-04-27 Biota Scientific Management Bycyclic nucleosides and nucleotides as therapeutic agents
TWI483950B (zh) 2009-09-21 2015-05-11 Gilead Sciences Inc 用於製備１’－取代碳核苷類似物之方法及中間物
US7973013B2 (en) 2009-09-21 2011-07-05 Gilead Sciences, Inc. 2'-fluoro substituted carba-nucleoside analogs for antiviral treatment
BR122021021135B1 (pt) * 2009-09-21 2022-08-30 Gilead Sciences, Inc Compostos análogos de 2-flúor substituído carba-nucleosídeo, composição farmacêutica e uso dos compostos análogos de 2´-flúoro substituído carbonucleosídeo
TW201201815A (en) * 2010-05-28 2012-01-16 Gilead Sciences Inc 1'-substituted-carba-nucleoside prodrugs for antiviral treatment

Also Published As

Publication number Publication date
UY33414A (es) 2011-12-30
HK1182387A1 (en) 2013-11-29
HRP20140370T1 (hr) 2014-05-23
JP2018162268A (ja) 2018-10-18
DK2576534T3 (da) 2014-04-22
RS53244B (sr) 2014-08-29
JP2018012706A (ja) 2018-01-25
SI2576534T1 (sl) 2014-06-30
US8415308B2 (en) 2013-04-09
JP5837577B2 (ja) 2015-12-24
PL2576534T3 (pl) 2014-07-31
WO2011150288A1 (en) 2011-12-01
JP2013528184A (ja) 2013-07-08
TW201201815A (en) 2012-01-16
JP6193332B2 (ja) 2017-09-06
CY1115479T1 (el) 2017-01-04
AR084389A1 (es) 2013-05-15
SMT201400048B (it) 2014-05-07
ES2465265T3 (es) 2014-06-05
JP2016094404A (ja) 2016-05-26
EP2576534A1 (en) 2013-04-10
EP2576534B1 (en) 2014-03-19
US20120020921A1 (en) 2012-01-26
PT2576534E (pt) 2014-05-29

Similar Documents

Publication Publication Date Title
ME01882B (me) 1 '-supstituisani-karba-nukleozidni prolekovi za antivirusni tretman
ME02656B (me) 2' -fluoro supstituisani karba-nukleozidni analozi za antiviralno lečenje
ES2792848T3 (es) Politerapia para el tratamiento de infecciones por VHB
RU2015123641A (ru) 2-алкинилзамещенные производные нуклеозидов, предназначенные для лечения вирусных заболеваний
JP2011521903A5 (me)
HRP20130048T1 (hr) Karba-nukleozidni analozi za antivirusnu terapiju
JP2012519691A5 (me)
RU2013119607A (ru) Полициклические гетероциклические соединения и способы их применения для лечения вирусных заболеваний
CA2972014A1 (en) Fused pyrimidine compounds for the treatment of hiv
JP2011079828A5 (me)
JP2012533630A5 (me)
HRP20160083T1 (hr) Makrocikliäśki inhibitori serinske proteaze virusa hepatitisa c izvedeni iz prolina
EA201201031A1 (ru) Ингибиторы вируса гепатита с
HRP20120866T1 (hr) Makrocikliäśni spojevi hinoksalina kao inhibitori hcv ns3 proteaze
HRP20161786T1 (hr) Pirolidinil urea, pirolidinil tiourea i pirolidinil gvanidin spojevi kao inhibitori trka kinaze
JP2011520906A5 (me)
RU2018105549A (ru) Производные бензодиазепина как ингибиторы rsv
JP2017505314A5 (me)
RU2012117395A (ru) Новые макроциклические ингибиторы репликации вируса гепатита с
BRPI0412761A (pt) inibidores de serino proteases, particularmente a protease ns3-ns4a do vhc
HRP20220899T1 (hr) Spojevi policikličkog karbamoilpiridona i njihova farmaceutska uporaba
CA2632626A1 (en) Ester prodrugs of 2'-fluoro-2'-alkyl-2'-deoxycytidines and their use in the treatment of hcv infection
HRP20151000T1 (hr) Antivirusni spojevi
JP2010526834A5 (me)
RU2014113539A (ru) Тетрациклические гетероциклические соединения и способы их применения для лечения вирусных заболеваний