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
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
EP11725838.4A EP2576534B1 (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 (75)

* 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
JP2006519753A (ja) 2002-11-15 2006-08-31 イデニクス（ケイマン）リミテツド ２’−分枝ヌクレオシドおよびフラビウイルス科ウイルス突然変異
CN102015714B (zh) 2008-04-23 2014-09-24 吉里德科学公司 用于抗病毒治疗的1’-取代的carba-核苷类似物
BR112012006180A2 (pt) 2009-09-21 2015-09-08 Gilead Sciences Inc processos e intermediários para a preparação de análogos de 1'-substituido carba-nucleosídeo
TW201201815A (en) * 2010-05-28 2012-01-16 Gilead Sciences Inc 1'-substituted-carba-nucleoside prodrugs for antiviral treatment
PT2596004E (pt) 2010-07-19 2014-11-28 Gilead Sciences Inc Métodos para a preparação de pró-fármacos de fosforamidato diastereomericamente puros
SG186830A1 (en) 2010-07-22 2013-02-28 Gilead Sciences Inc Methods and compounds for treating paramyxoviridae virus infections
AU2011349844B2 (en) 2010-12-20 2017-06-01 Gilead Sciences, Inc. Combinations for treating HCV
WO2012154321A1 (en) 2011-03-31 2012-11-15 Idenix Pharmaceuticals, Inc. Compounds and pharmaceutical compositions for the treatment of viral infections
TW201329096A (zh) 2011-09-12 2013-07-16 Idenix Pharmaceuticals Inc 經取代羰氧基甲基磷酸醯胺化合物及用於治療病毒感染之藥學組成物
AP2014007575A0 (en) 2011-09-16 2012-04-30 Gilead Pharmasset Llc Methods for treating HCV
US8507460B2 (en) 2011-10-14 2013-08-13 Idenix Pharmaceuticals, Inc. Substituted 3′,5′-cyclic phosphates of purine nucleotide compounds and pharmaceutical compositions for the treatment of viral infections
US9109001B2 (en) 2012-05-22 2015-08-18 Idenix Pharmaceuticals, Inc. 3′,5′-cyclic phosphoramidate prodrugs for HCV infection
US9296778B2 (en) 2012-05-22 2016-03-29 Idenix Pharmaceuticals, Inc. 3′,5′-cyclic phosphate prodrugs for HCV infection
AU2013266393B2 (en) * 2012-05-22 2017-09-28 Idenix Pharmaceuticals Llc D-amino acid compounds for liver disease
PL2861611T3 (pl) 2012-05-25 2017-08-31 Janssen Sciences Ireland Uc Nukleozydy uracylowe spirooksetanu
US9192621B2 (en) 2012-09-27 2015-11-24 Idenix Pharmaceuticals Llc Esters and malonates of SATE prodrugs
AP2015008384A0 (en) 2012-10-08 2015-04-30 Univ Montpellier Ct Nat De La Rech Scient 2'-Chloro nucleoside analogs for hcv infection
US9457039B2 (en) 2012-10-17 2016-10-04 Merck Sharp & Dohme Corp. 2′-disubstituted nucleoside derivatives and methods of use thereof for the treatment of viral diseases
US9242988B2 (en) 2012-10-17 2016-01-26 Merck Sharp & Dohme Corp. 2′-cyano substituted nucleoside derivatives and methods of use thereof for the treatment of viral diseases
EP2909222B1 (en) 2012-10-22 2021-05-26 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
SG11201506021XA (en) 2013-01-31 2015-08-28 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
WO2014137926A1 (en) 2013-03-04 2014-09-12 Idenix Pharmaceuticals, Inc. 3'-deoxy nucleosides for the treatment of hcv
WO2014160484A1 (en) 2013-03-13 2014-10-02 Idenix Pharmaceuticals, Inc. Amino acid phosphoramidate pronucleotides of 2'-cyano, azido and amino nucleosides for the treatment of hcv
EP2981542B1 (en) 2013-04-01 2021-09-15 Idenix Pharmaceuticals LLC 2',4'-fluoro nucleosides for the treatment of hcv
EP3004130B1 (en) 2013-06-05 2019-08-07 Idenix Pharmaceuticals LLC. 1',4'-thio nucleosides for the treatment of hcv
US20150037282A1 (en) 2013-08-01 2015-02-05 Idenix Pharmaceuticals, Inc. 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
US10202411B2 (en) 2014-04-16 2019-02-12 Idenix Pharmaceuticals Llc 3′-substituted methyl or alkynyl nucleosides nucleotides for the treatment of HCV
EP3137454A1 (en) 2014-04-28 2017-03-08 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
TWI687432B (zh) 2014-10-29 2020-03-11 美商基利科學股份有限公司 絲狀病毒科病毒感染之治療
JP7381190B2 (ja) 2014-12-26 2023-11-15 エモリー・ユニバーシテイ Ｎ４－ヒドロキシシチジン及び誘導体並びにそれに関連する抗ウイルス用途
CA3182565A1 (en) 2015-03-06 2016-09-15 Atea Pharmaceuticals, Inc. .beta.-d-2'-deoxy-2'-.alpha.-fluoro-2'-.beta.-c-substituted-2-modified-n6-substituted purine nucleotides for hcv treatment
EP3288957A4 (en) 2015-05-01 2019-01-23 Cocrystal Pharma, Inc. NUCLEOSIDE ANALOGUE FOR THE TREATMENT OF VIRUSES OF THE FLAVIVIIDAE FAMILY AND CANCER
PT3331894T (pt) 2015-08-05 2021-04-07 Metro Int Biotech Llc Derivados mononucleotídicos de nicotinamida e suas utilizações
BR122020020217B1 (pt) 2015-09-16 2021-08-17 Gilead Sciences, Inc Uso de um composto antiviral ou sal do mesmo para o tratamento de uma infecção por arenaviridae
TWI753892B (zh) 2016-03-28 2022-02-01 美商英塞特公司 作為ｔａｍ抑制劑之吡咯并三嗪化合物
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
EP3865136A1 (en) 2016-09-07 2021-08-18 ATEA Pharmaceuticals, Inc. 2'-substituted-n6-substituted purine nucleotides for corona virus treatment
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
FI3577124T3 (fi) 2017-02-01 2025-02-13 Atea Pharmaceuticals Inc Nukleotidihemisulfaattisuola hepatiitti C -viruksen hoitoon
EP4331677A3 (en) 2017-03-14 2024-05-29 Gilead Sciences, Inc. Methods of treating feline coronavirus infections
CA3178212A1 (en) 2017-05-01 2018-11-08 Gilead Sciences, Inc. Crystalline forms of (s)-2-ethylbutyl 2-(((s)-(((2r,3s,4r,5r)-5-(4-aminopyrrolo[2,1-f] [1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy) phosphoryl)amino)propanoate
PL3651734T3 (pl) 2017-07-11 2025-03-31 Gilead Sciences, Inc. Kompozycje zawierające inhibitor polimerazy rna i cyklodekstrynę do leczenia infekcji wirusowych
KR102626210B1 (ko) 2017-12-07 2024-01-18 에모리 유니버시티 N4-하이드록시사이티딘 및 유도체 및 이와 관련된 항-바이러스 용도
KR20200140865A (ko) 2018-04-10 2020-12-16 아테아 파마슈티컬즈, 인크. 간경변증을 갖는 hcv 감염 환자의 치료
US11660307B2 (en) 2020-01-27 2023-05-30 Gilead Sciences, Inc. Methods for treating SARS CoV-2 infections
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
CN115135383B (zh) 2020-02-18 2024-06-11 吉利德科学公司 抗病毒化合物
TWI775313B (zh) 2020-02-18 2022-08-21 美商基利科學股份有限公司 抗病毒化合物
TWI883391B (zh) 2020-02-18 2025-05-11 美商基利科學股份有限公司 抗病毒化合物
TWI791193B (zh) * 2020-02-18 2023-02-01 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
TWI785528B (zh) 2020-03-12 2022-12-01 美商基利科學股份有限公司 1’-氰基核苷之製備方法
EP4125810A1 (en) * 2020-03-22 2023-02-08 InspirMed Corp. Composition of antiviral agent for use in prophylactic or post-exposure treatment of infectious or respiratory diseases
EP4132651A1 (en) 2020-04-06 2023-02-15 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
TW202532084A (zh) 2020-05-29 2025-08-16 美商基利科學股份有限公司 瑞德西韋之治療方法
WO2021262826A2 (en) * 2020-06-24 2021-12-30 Gilead Sciences, Inc. 1'-cyano nucleoside analogs and uses thereof
CN116323630A (zh) 2020-08-24 2023-06-23 吉利德科学公司 磷脂化合物及其用途
PT4204421T (pt) 2020-08-27 2024-06-25 Gilead Sciences Inc Compostos e métodos para o tratamento de infeções virais
KR20230079427A (ko) 2020-10-08 2023-06-07 머크 샤프 앤드 돔 엘엘씨 신규 디아실글리세리드 o-아실트랜스퍼라제 2 억제제로서의 옥스인돌 유도체의 제조
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
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
JP7688152B2 (ja) 2021-04-16 2025-06-03 ギリアード サイエンシーズ， インコーポレイテッド アミドを使用してカルバヌクレオシドを調製する方法
MX2023014898A (es) 2021-06-17 2024-04-29 Atea Pharmaceuticals Inc Terapia combinada anti-vhc ventajosa.
KR20240049311A (ko) 2021-08-18 2024-04-16 길리애드 사이언시즈, 인코포레이티드 인지질 화합물 및 이의 제조 및 사용 방법
JP2025508942A (ja) 2022-03-02 2025-04-10 ギリアード サイエンシーズ， インコーポレイテッド ウイルス感染症の治療のための化合物及び方法
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
KR20030005197A (ko) 2000-02-18 2003-01-17 샤이어 바이오켐 인코포레이티드 뉴클레오시드유도체를 이용한 플라비바이러스 감염의 치료또는 예방 방법
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
KR20090089922A (ko) 2000-10-18 2009-08-24 파마셋 인코포레이티드 바이러스 감염 및 비정상적인 세포 증식의 치료를 위한 변형된 뉴클레오시드
SI1355916T1 (sl) * 2001-01-22 2007-04-30 Merck & Co Inc Nukleozidni derivati kot inhibitorji RNA-odvisne RNA virusne polimeraze
JP2005536440A (ja) 2001-09-28 2005-12-02 イデニクス（ケイマン）リミテツド ４’位が修飾されたヌクレオシドを使用するフラビウイルスおよびペスチウイルスの治療のための方法および組成物
AU2003233667A1 (en) 2002-05-23 2003-12-12 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
JP2006519753A (ja) 2002-11-15 2006-08-31 イデニクス（ケイマン）リミテツド ２’−分枝ヌクレオシドおよびフラビウイルス科ウイルス突然変異
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
PL2114980T3 (pl) 2007-01-12 2012-11-30 Biocryst Pharm Inc Przeciwwirusowe analogi nukleozydów
AU2008251555B2 (en) * 2007-05-10 2012-08-30 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
CN102015714B (zh) * 2008-04-23 2014-09-24 吉里德科学公司 用于抗病毒治疗的1’-取代的carba-核苷类似物
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.
WO2010002877A2 (en) 2008-07-03 2010-01-07 Biota Scientific Management Bycyclic nucleosides and nucleotides as therapeutic agents
SMT201700091T1 (it) 2009-09-21 2017-03-08 Gilead Sciences Inc ANALOGHI CARBA-NUCLEOSIDlCI2'-FLUORO SOSTITUITI PER TRATTAMENTO ANTIVIRALE
US7973013B2 (en) 2009-09-21 2011-07-05 Gilead Sciences, Inc. 2'-fluoro substituted carba-nucleoside analogs for antiviral treatment
BR112012006180A2 (pt) 2009-09-21 2015-09-08 Gilead Sciences Inc processos e intermediários para a preparação de análogos de 1'-substituido carba-nucleosídeo
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
AR084389A1 (es) 2013-05-15
SI2576534T1 (sl) 2014-06-30
EP2576534B1 (en) 2014-03-19
UY33414A (es) 2011-12-30
DK2576534T3 (da) 2014-04-22
JP6193332B2 (ja) 2017-09-06
PL2576534T3 (pl) 2014-07-31
CY1115479T1 (el) 2017-01-04
JP2018162268A (ja) 2018-10-18
WO2011150288A1 (en) 2011-12-01
SMT201400048B (it) 2014-05-07
HRP20140370T1 (hr) 2014-05-23
US20120020921A1 (en) 2012-01-26
JP2013528184A (ja) 2013-07-08
EP2576534A1 (en) 2013-04-10
US8415308B2 (en) 2013-04-09
PT2576534E (pt) 2014-05-29
TW201201815A (en) 2012-01-16
RS53244B (sr) 2014-08-29
ES2465265T3 (es) 2014-06-05
JP5837577B2 (ja) 2015-12-24
JP2018012706A (ja) 2018-01-25
JP2016094404A (ja) 2016-05-26
HK1182387A1 (en) 2013-11-29

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
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)
JP2013538230A5 (me)
JP2013514359A5 (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)
RU2012117395A (ru) Новые макроциклические ингибиторы репликации вируса гепатита с
JP2017505314A5 (me)
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
RU2014113539A (ru) Тетрациклические гетероциклические соединения и способы их применения для лечения вирусных заболеваний
RU2018127728A (ru) Слитые трициклические гетероциклические соединения в качестве ингибиторов интегразы вич
RU2014107484A (ru) ПРИМЕНЕНИЕ СОЕДИНЕНИЙ 2,3-ДИГИДРОИМИДАЗО[1,2-с]ПИРИМИДИН-5(1H)-ОНА В КАЧЕСТВЕ ИНГИБИТОРОВ LP-PLA2