SI2227482T1 - 2',4'-substituirani nukleozidi kot antivirusna sredstva - Google Patents

2',4'-substituirani nukleozidi kot antivirusna sredstva Download PDF

Info

Publication number
SI2227482T1
SI2227482T1 SI200831917T SI200831917T SI2227482T1 SI 2227482 T1 SI2227482 T1 SI 2227482T1 SI 200831917 T SI200831917 T SI 200831917T SI 200831917 T SI200831917 T SI 200831917T SI 2227482 T1 SI2227482 T1 SI 2227482T1
Authority
SI
Slovenia
Prior art keywords
alkyl
optionally substituted
alkenyl
alkynyl
acyl
Prior art date
Application number
SI200831917T
Other languages
English (en)
Inventor
Michael J. Sofia
Jinfa Du
Original Assignee
Gilead Pharmasset LLC c/o 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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=40373557&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=SI2227482(T1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Gilead Pharmasset LLC c/o Gilead Sciences, Inc. filed Critical Gilead Pharmasset LLC c/o Gilead Sciences, Inc.
Publication of SI2227482T1 publication Critical patent/SI2227482T1/sl

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/06—Pyrimidine radicals
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • A61K31/7072—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
    • 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
    • A61P31/04—Antibacterial agents
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • 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
    • A61P31/20—Antivirals for DNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/06—Pyrimidine radicals
    • C07H19/073—Pyrimidine radicals with 2-deoxyribosyl as the saccharide radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/14—Pyrrolo-pyrimidine radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/16—Purine radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/16—Purine radicals
    • C07H19/173—Purine radicals with 2-deoxyribosyl as the saccharide radical

Landscapes

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

Claims (9)

  1. 2’,4’-SUBSTITUIRANI NUKLEOZIDI KOT ANTIVIRUSNA SREDSTVA EP 2 227 482 B1 PATENTNI ZAHTEVKI
    1. Spojina s formulo
    kjer za strukturo A ali A' (a) je R2 neodvisno CH3, CH2F, CHF2, CF3, CN, C2-4 alkenil, C2^ alkinil, or C1-4 alkil po izbiri susbtituiran z amino ali 1 do 3 fluorovimi atomi; (b) R is H, fosfat, vključno s 5'-monofosfatom, 5',3'-cikličnim fosfatom, difosfatom, ali trifosfatom, H-fosfonatom, acil, alkil, vključno s C1-8 alkilom, O-substituiranim karboksialkilaminom, sulfonat ester, vključno s alkilom ali arilalkil sulfonil, vključno z metansulfonilom in benzilom, kjer je fenilna skupina po izbiri substituirana, lipid, vključno s fosfolipidom, L ali D-amino acid, karbohidrat, peptid, ali kolesterol; (c) je R3 neodvisno OH, H, C1-4 alkil, C2-4 alkenil, C2-4 alkinil, vinil, N3, CN, Cl, Br, F, I, NO2, C(0)0(Ci-4 alkil), C(0)0(Ci-4 alkil), C(0)0(C2-4 alkinil), C(0)0(C2-4 alkenil), 0(Ci-io acil), 0(Ci-4 alkil), 0(C2-4 alkenil), SH, S(Ci-4 acil), S(Ci-4 alkil), S(C2-4 alkinil), S(Ci-4 alkenil), S0(Ci-4 acil), S0(Ci-4 alkil), SO(C2-4 alkinil), SO(C2-4 alkenil), S02(Ci-4 acyl), S02(Ci-4alkil), S02(C2-4 alkinil), S02(C2-4 alkenil), 0S(0)2(Ci-4 acyl), 0S(0)2(Ci-4 alkil), 0S(0)2(C2-4 alkenil), NH2, NH(Ci-4 alkil), NNR2-4 alkenil), NNR2-4 alkinil), NH(Ci-4 acil), N(Ci-4 alkil>2, N(Ci-ie acil>2, kjer so alkil, alkinil, alkenil in vinil po izbiri substituirani z N3, CN, enim do tremi halogeni (Cl, Br, F, I), NO2, C(0)0(Ci-4 alkil), C(0)0(Ci-4 alkil), C(0)0(C2-4 alkinil), C(0)0(C2^ alkenil), 0(Ci-4 acil), 0(Ci-4 alkil), 0(C2-4 alkenil), SH, S(Ci-4 acil), S(Ci-4 alkil), S(C2-4 alkinil), S(C2-4 alkenil), SO(Ci-4 acil), SO(Ci-4 alkil), SO(C2-4 alkinil), SO(C2-4 alkenil), S02(Ci-4 acil), S02(Ci-4 alkil), S02(C2-4 alkinil), S02(C2-4 alkenil), 0S(0)2(Ci-4 acyl), 0S(0)2(Ci-4 alkil), 0S(0)2(C2-4 alkenil), NH2, NH(Ci-4 alkil), NH(C2-4 alkenil), NNR2-4 alkinil), NH(Ci-4 acil), N(Ci-4 alkil)2, N(Ci-4 acil)2; (d) je R4 neodvisno CN, alkenil or alkinil; (e) R in R3 lahko skupaj oblikujeta 5',3’-ciklični fosfat; (f) je osnova naravno nastala ali modificirana purinska ali pirimidinska osnova predstavljena z naslednjima strukturama:
    kjer za a in b je Z NaliCR8; so R5, R6, in R7 neodvisno H, F, Cl, Br, I, OH, OR', SH, SR', NH2, NHR', NR'2 (dva R' lahko oblikujeta nasičene ali nenasičene obroče, ali nasičene ali nenasičene heterociklične obroče), alkil od Ci-Ce, halogeniran (F, Cl, Br, I) alkil od Ci-Ce, nižji alkenil od C2-C6, halogeniran (F, Cl, Br, I) nižji alkenil of C2-C6, nižji alkinil od C2-C6 kut je C=CH, halogeniran (F, Cl, Br, I) nižji alkinil od C2-C6, nižji alkoksi od Ci-Ce, halogeniran (F, Cl, Br, I) nižji alkoksi od Ci-Ce, CO2H, C02R\ CONH2, CONHR', CONR'2, CH=CHC02H, or CH=CHC02R', kjer je R' po izbiri substituiran alkil, ki vključuje, toda ni omejen na, po izbiri substituiran C1-20 alkil, po izbiri substituiran C1-10 alkil, po izbiri substituiran C1-8 alkil; po izbiri substituiran cikloalkil; po izbiri substituiran alkinil od C2-C6, po izbiri substituiran nižji alkenil od C2-C6, ali po izbiri substituiran acil, ki vključuje, toda ni omejen na C(O) alkil, C(0)(Ci-2o alkil), C(0)(Ci-io alkil), ali C(0)(Ci-8 alkil), po izbiri substituiran aril, po izbiri substituiran C1-C4 alkilariloksi, heteroaril, po izbiri substituiran C1-C4 alkilheteroaril, po izbiri substituiran alkoksi C1-20 alkil, po izbiri substituiran amino C1-20 alkil, po izbiri substituiran fluoro C1-20 alkil; je R8 neodvisno H, halogen (vključno F, Cl, Br, I), OH, OR', SH, SR', NH2, NHR', NR'2 (dva R' lahko oblikujeta nasičene ali nenasičene obroče, ali nasičene ali nenasičene heterociklične obroče), NO2, alkil od C1-C6, halogeniran (F, Cl, Br, I) alkil od Ci-Ce, nižji alkenil of C2-C6, halogeniran (F, Cl, Br, I) nižji alkenil od C2-C6, nižji alkinil od C2-C6, halogeniran (F, Cl, Br, I) nižji alkinil od C2-C6, nižji alkoksi od C1-C6, halogeniran (F, Cl, Br, I) nižji alkoksi od Ci-Ce, CO2H, C02R', CONH2, CONHR', CONR'2, CH=CHC02H, or CH=CHC02R\ kjer je R' po izbiri substituiran alkil, ki vključuje, toda ni omejen na, po izbiri substituiran C1-20 alkil, po izbiri substituiran C1-10 alkil, po izbiri substituiran C1-8 alkil; po izbiri substituiran cikloalkil; po izbiri substituiran alkinil od C2-C6, po izbiri substituiran nižji alkenil od C2-C6, ali po izbiri substituiran acil, ki vključuje, toda ni omejen na C(O) alkil, C(0)(Ci-2o alkil), C(0)(Ci-io alkil), ali C(0)(Ci-e alkil), po izbiri substituiran aril, po izbiri substituiran C1-C4 alkil-ariloksi, heteroaril, po izbiri substituiran C1-C4 alkil-heteroaril, po izbiri substituiran alkoksi C1-20 alkil, po izbiri substituiran amino C1-20 alkil, po izbiri substituiran fluoro C1-20 alkil; ali je osnova lahko izbrana iz skupine s formulo c
    kjer velja za strukturo c, če je Z udeležen v pi vezi (dvojna vez), je Z neodvisno izbran izmed N ali C-G; ali, če Z ni udeležen v pi vezi (dvojna vez) je Z neodvisno izbran izmed O, S, Se, NR, NOR, NNR2, CO, CS, CNR, SO, S(0)2, SeO, Se(0)2, ali C(G)2; vsak G je neodvisno izbran izmed skupine, ki jo sestavljajo H, halogen, OR, SR, NR2, NROR, N3i COOR, CN, CONR2, C(S)NR2, C(=NR)NR2, in R; in kjer katerakoli dva sosednja Z nista oba izbrana izmed O, S, in Se, ali nista oba izbrana izmed CO, CS, CNNR, SO, S(0)2, SeO in Se(0)2; kjer, če je X udeležen v pi vezi (dvojna vez) je X C; ali če X ni udeležen v pi vezi (dvojna vez), je X CR ali N; kjer, če je R" udeležen v pi vezi (dvojna vez), je R" O, S, Se, NR, NOR ali NNR2; ali če R" ni udeležen v pi vezi (dvojna vez), je R" OR, SR, F, Cl, R, ali SeR; in črtkane linije (--) označujejo možno pi ali dvojno vez; je vsak R neodvisno izbran iz skupine, ki jo H, CF3, po izbiri substituiran alkil, po izbiri substituiran alkenil, po izbiri substituiran alkinil, po izbiri substituiran aril, po izbiri substituiran acil, po izbiri substituiran cikloalkil, po izbiri substituiran cikloalkenil, po izbiri substituiran heteroaril, po izbiri substituiran heterociklil, in po izbiri substituiran arilalkil; ali je osnova lahko struktura, izbrana iz skupine, ki jo sestavljajo strukture d-n
    kjer so Z, X, in R" definirani kot c strukturi c; je osnova lahko struktura izbrana iz skupine, ki jo sestavljajo strukture o-ff
    kjer sta G in R definirana kot v strukturi c; je osnova lahko struktura gg
    gg kjer je vsak Z' neodvisno N (če sodeluje v pi vezi) ali NR (če ne sodeluje v pi vezi) in R", R, in Z so definirani kot v strukturi c; je osnova lahko struktura hh
    Jih kjer je vsak Z' neodvisno N (če sodelujev pi vezi) ali NR (če ne sodeluje v pi vezi), in vsak Z je neodvisno CG (če sodeluje v pi vezi) ali >C(G)2 (če ne sodeluje v pi vezi), kjer sta R" in G definirana kot v strukturi c; je osnova lahko struktura ii
    U kjer sta R in G definirana kot v strukturi c; je osnova lahko struktura jj
    jj kjer sta R in G definirana kot v strukturi c; ali njena farmacevtsko sprejemljivo sol, tavtomera, farmacevtsko sprejemljiva sol ali tavtomera, sol (kislinska ali bazična adicijska sol), hidrat, solvat ali kristalna oblika.
  2. 2. Spojina po zahtevku 1, kjer je za strukturo A ali A' R4 neodvisno CN, vinil ali alkinil.
  3. 3. Farmacevtski sestavek za zdravljenje HBV, HCV ali HIV, ki vključuje farmacevtsko efektivno terapevtska količina spojine po zahtevku 1 ali 2 v farmacevtsko sprejemljivem nosilcu ali razredčilu.
  4. 4. Spojina po zahtevku 1 ali 2, kjer je spojina predstavljena s formulo A.
  5. 5. Spojina po zahtevku 1 ali 2, po izbiri v kombinaciji z enim ali več protivirusnimi, antibakterijskimi ali antiproliferacijskimi sredstvi, za uporabo pri zdravljenju in/ali profilaksi gostitelja okuženega s HBV, HCV ali HIV.
  6. 6. Uporaba spojine po zahtevku 1 ali 2 pri izdelavi zdravila za zdravljenje in/ali profilakso katerega koli stanja, ki je posledica infekcije s HBV, HCV ali HIV, po izbiri v kombinaciji z enim ali več protivirusnimi, antibakterijskimi ali antiproliferativnimi sredstvi.
  7. 7. Postopek za pripravo zdravila, ki obsega kombiniranje farmacevtsko učinkovitega nosilca s spojino po zahtevku 1 ali 2, po izbiri v kombinaciji z enim ali več protivirusnimi, antibakterijskimi ali antiproliferacijskimi sredstvi.
  8. 8. Spojina po zahtevku 1 ali 2, kjer je spojina izbrana izmed naslednjih spojin:
  9. 9. Postopek, ki vsebuje : (1) deoksidiranje 2'-C-pozicije v spojini predstavljeni z 1 ali 1',
    da dobimo spojino, predstavljeno z 2 ali 2'
    in (2) derivatizacija spojine predstavljene z 2 ali 2', da dobimo spojino po zahtevku 1 ali 2.
SI200831917T 2007-11-20 2008-11-17 2',4'-substituirani nukleozidi kot antivirusna sredstva SI2227482T1 (sl)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US98929607P 2007-11-20 2007-11-20
US12/271,388 US20090318380A1 (en) 2007-11-20 2008-11-14 2',4'-substituted nucleosides as antiviral agents
PCT/US2008/083787 WO2009067409A1 (en) 2007-11-20 2008-11-17 2',4'-substituted nucleosides as antiviral agents
EP08852934.2A EP2227482B1 (en) 2007-11-20 2008-11-17 2',4'-substituted nucleosides as antiviral agents

Publications (1)

Publication Number Publication Date
SI2227482T1 true SI2227482T1 (sl) 2018-03-30

Family

ID=40373557

Family Applications (1)

Application Number Title Priority Date Filing Date
SI200831917T SI2227482T1 (sl) 2007-11-20 2008-11-17 2',4'-substituirani nukleozidi kot antivirusna sredstva

Country Status (21)

Country Link
US (4) US20090318380A1 (sl)
EP (3) EP2848624B1 (sl)
JP (1) JP5492785B2 (sl)
CN (1) CN101932590B (sl)
AR (1) AR069634A1 (sl)
AU (1) AU2008326569B2 (sl)
CA (1) CA2706327C (sl)
CL (1) CL2008003431A1 (sl)
ES (3) ES2663086T3 (sl)
HK (2) HK1149017A1 (sl)
IL (1) IL205895A0 (sl)
NO (1) NO2227482T3 (sl)
NZ (1) NZ601486A (sl)
PA (1) PA8804701A1 (sl)
PE (1) PE20091424A1 (sl)
PL (1) PL2227482T3 (sl)
PT (2) PT2631239E (sl)
SI (1) SI2227482T1 (sl)
TW (1) TW200936603A (sl)
UY (1) UY31476A1 (sl)
WO (1) WO2009067409A1 (sl)

Families Citing this family (87)

* 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
NZ547204A (en) 2000-05-26 2008-01-31 Idenix Cayman Ltd Methods and compositions for treating flaviviruses and pestiviruses
HUE033832T2 (en) 2002-11-15 2018-01-29 Idenix Pharmaceuticals Llc 2'-methyl nucleosides in combination with interferon and Flaviviridae mutation
ES2586668T3 (es) 2003-05-30 2016-10-18 Gilead Pharmasset Llc Análogos de nucleósidos fluorados modificados
AU2006294807B2 (en) * 2005-09-26 2013-01-17 Gilead Pharmasset Llc Modified 4'-nucleosides as antiviral agents
GB0625283D0 (en) 2006-12-19 2007-01-24 Cyclacel Ltd Combination
CN100532388C (zh) * 2007-07-16 2009-08-26 郑州大学 2’-氟-4’-取代-核苷类似物、其制备方法及应用
US20090318380A1 (en) 2007-11-20 2009-12-24 Pharmasset, Inc. 2',4'-substituted nucleosides as antiviral agents
US8227431B2 (en) 2008-03-17 2012-07-24 Hetero Drugs Limited Nucleoside derivatives
US8173621B2 (en) 2008-06-11 2012-05-08 Gilead Pharmasset Llc Nucleoside cyclicphosphates
NZ593647A (en) 2008-12-23 2013-08-30 Gilead Pharmasset Llc Synthesis of purine nucleosides
EP2376514A2 (en) 2008-12-23 2011-10-19 Pharmasset, Inc. Nucleoside analogs
MX2011006891A (es) 2008-12-23 2011-10-06 Pharmasset Inc Fosforamidatos de nucleosidos.
BR112012007122A2 (pt) 2009-09-29 2016-07-12 Janssen Products Lp derivados de fosforamidatos de nucleosídeos
ES2437933T3 (es) * 2010-01-28 2014-01-15 F. Hoffmann-La Roche Ag 4'-azido-nucleósidos como compuestos anti-VHC
AU2011235112B2 (en) 2010-03-31 2015-07-09 Gilead Pharmasset Llc Nucleoside phosphoramidates
CN102351931B (zh) * 2010-09-07 2014-01-22 河南省科学院高新技术研究中心 嘧啶核苷衍生物、合成方法及其在制备抗肿瘤、抗病毒药物中的应用
EP2619215B1 (en) 2010-09-22 2018-09-05 Alios Biopharma, Inc. Azido nucleosides and nucleotide analogs
GEP20156313B (en) 2010-09-22 2015-07-10 Alios Biopharma Inc Substituted nucleotide analogs
AU2011336632B2 (en) 2010-11-30 2015-09-03 Gilead Pharmasset Llc Compounds
US9243025B2 (en) 2011-03-31 2016-01-26 Idenix Pharmaceuticals, Llc Compounds and pharmaceutical compositions for the treatment of viral infections
WO2013039920A1 (en) 2011-09-12 2013-03-21 Idenix Pharmaceuticals, Inc. Substituted carbonyloxymethylphosphoramidate compounds and pharmaceutical compositions for the treatment of viral infections
CN102286047A (zh) * 2011-09-14 2011-12-21 郑州大学 2’-脱氧-2’-氟-4’-三氮唑取代-β-D胞苷类似物、其制备方法及其应用
TW201331221A (zh) 2011-10-14 2013-08-01 Idenix Pharmaceuticals Inc 嘌呤核苷酸化合物類之經取代的３’，５’－環磷酸酯及用於治療病毒感染之醫藥組成物
EP2794630A4 (en) 2011-12-22 2015-04-01 Alios Biopharma Inc SUBSTITUTED PHOSPHORTHIOAT NUCLEOTIDE ANALOGUE
HUE041509T2 (hu) 2011-12-22 2019-05-28 Janssen Biopharma Inc Szubsztituált nukleozidok, nukleotidok és ezek analógjai
CN102603836A (zh) * 2012-02-10 2012-07-25 郑州大学 五味子丙素简化物、类似物及其制备方法和应用
US9441007B2 (en) 2012-03-21 2016-09-13 Alios Biopharma, Inc. Substituted nucleosides, nucleotides and analogs thereof
USRE48171E1 (en) 2012-03-21 2020-08-25 Janssen Biopharma, Inc. Substituted nucleosides, nucleotides and analogs thereof
CN104321333A (zh) 2012-03-21 2015-01-28 沃泰克斯药物股份有限公司 硫代氨基磷酸酯核苷酸前药的固体形式
WO2013142157A1 (en) 2012-03-22 2013-09-26 Alios Biopharma, Inc. Pharmaceutical combinations comprising a thionucleotide analog
AU2013266393B2 (en) 2012-05-22 2017-09-28 Idenix Pharmaceuticals Llc D-amino acid compounds for liver disease
WO2013177188A1 (en) 2012-05-22 2013-11-28 Idenix Pharmaceuticals, Inc. 3',5'-cyclic phosphoramidate prodrugs for hcv infection
EP2852605B1 (en) 2012-05-22 2018-01-31 Idenix Pharmaceuticals LLC 3',5'-cyclic phosphate prodrugs for hcv infection
EP2852583A1 (en) 2012-05-23 2015-04-01 Bristol-Myers Squibb Company Sulfilimine and sulphoxide methods for producing festinavir
SG11201407336PA (en) 2012-05-25 2015-03-30 Janssen Sciences Ireland Uc Uracyl spirooxetane nucleosides
US9556216B2 (en) 2012-08-31 2017-01-31 Novartis Ag 2′-Ethynyl nucleoside derivatives for treatment of viral infections
US9192621B2 (en) 2012-09-27 2015-11-24 Idenix Pharmaceuticals Llc Esters and malonates of SATE prodrugs
GEP201706723B (en) 2012-10-08 2017-08-25 Idenix Pharmaceuticals Llk 2'-chloro nucleoside analogs for hcv infection
WO2014066239A1 (en) 2012-10-22 2014-05-01 Idenix Pharmaceuticals, Inc. 2',4'-bridged nucleosides for hcv infection
CA2891125A1 (en) * 2012-11-19 2014-05-22 Merck Sharp & Dohme Corp. 2 -alkynyl substituted nucleoside derivatives for treating viral diseases
WO2014099941A1 (en) 2012-12-19 2014-06-26 Idenix Pharmaceuticals, Inc. 4'-fluoro nucleosides for the treatment of hcv
CA2894542C (en) * 2012-12-21 2023-10-31 Alios Biopharma, Inc. Substituted nucleosides, nucleotides and analogs thereof
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
WO2014165542A1 (en) 2013-04-01 2014-10-09 Idenix Pharmaceuticals, Inc. 2',4'-fluoro nucleosides for the treatment of hcv
CN105705511A (zh) 2013-04-12 2016-06-22 艾其林医药公司 用于治疗hcv的氘化核苷前药
WO2014172264A1 (en) 2013-04-16 2014-10-23 Bristol-Myers Squibb Company Method for producing festinavir using 5-methyluridine as starting material
AU2014265293B2 (en) 2013-05-16 2019-07-18 Riboscience Llc 4'-Fluoro-2'-methyl substituted nucleoside derivatives
US20180200280A1 (en) 2013-05-16 2018-07-19 Riboscience Llc 4'-Fluoro-2'-Methyl Substituted Nucleoside Derivatives as Inhibitors of HCV RNA Replication
EP3004130B1 (en) 2013-06-05 2019-08-07 Idenix Pharmaceuticals LLC. 1',4'-thio nucleosides for the treatment of hcv
WO2014201122A1 (en) 2013-06-13 2014-12-18 Bristol-Myers Squibb Company Tert-butyl-sulphoxide method for producing festinavir
CN104086612A (zh) * 2013-07-17 2014-10-08 郑州大学 4-取代胺基-2′-脱氧-2′-氟-4′-叠氮-β-D-胞苷类核苷化合物、制备方法及其应用
WO2015017713A1 (en) 2013-08-01 2015-02-05 Idenix Pharmaceuticals, Inc. D-amino acid phosphoramidate pronucleotides of halogeno pyrimidine compounds for liver disease
US9862743B2 (en) 2013-10-11 2018-01-09 Alios Biopharma, Inc. Substituted nucleosides, nucleotides and analogs thereof
US10683321B2 (en) 2013-12-18 2020-06-16 Idenix Pharmaceuticals Llc 4′-or nucleosides for the treatment of HCV
WO2015143712A1 (en) 2014-03-28 2015-10-01 Merck Sharp & Dohme Corp. 4'-substituted nucleoside reverse transcriptase inhibitors
US10202411B2 (en) 2014-04-16 2019-02-12 Idenix Pharmaceuticals Llc 3′-substituted methyl or alkynyl nucleosides nucleotides for the treatment of HCV
AP2016009653A0 (en) 2014-06-24 2016-12-31 Alios Biopharma Inc Substituted nucleosides, nucleotides and analogs thereof
MA41213A (fr) * 2014-12-19 2017-10-24 Alios Biopharma Inc Nucléosides substitués, nucléotides et analogues de ceux-ci
CN104558080A (zh) * 2015-02-03 2015-04-29 西安新通药物研究有限公司 环状磷酸酯合成的新方法
KR102363946B1 (ko) 2015-03-06 2022-02-17 아테아 파마슈티컬즈, 인크. HCV 치료를 위한 β-D-2'-데옥시-2'-α-플루오로-2'-β-C-치환된-2-변형된-N6-치환된 퓨린 뉴클레오티드
WO2017024310A1 (en) 2015-08-06 2017-02-09 Chimerix, Inc. Pyrrolopyrimidine nucleosides and analogs thereof useful as antiviral agents
JP6767011B2 (ja) * 2015-09-18 2020-10-14 ヤマサ醤油株式会社 抗ｄｎａウィルス活性などの生理活性を有するヌクレオシド誘導体
CA2998646C (en) 2015-09-23 2021-05-18 Merck Sharp & Dohme Corp. 4'-substituted nucleoside reverse transcriptase inhibitors and preparations thereof
CN109562107A (zh) 2016-05-10 2019-04-02 C4医药公司 用于靶蛋白降解的杂环降解决定子体
EP3455218A4 (en) 2016-05-10 2019-12-18 C4 Therapeutics, Inc. C3 CARBON-BASED GLUTARIMIDE DEGRONIMERS FOR TARGET PROTEIN REDUCTION
CN109562113A (zh) 2016-05-10 2019-04-02 C4医药公司 用于靶蛋白降解的螺环降解决定子体
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
WO2018013937A1 (en) 2016-07-14 2018-01-18 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
KR20190043602A (ko) 2016-09-07 2019-04-26 아테아 파마슈티컬즈, 인크. Rna 바이러스 치료를 위한 2'-치환된-n6-치환된 퓨린 뉴클레오티드
EP3538108A4 (en) * 2016-11-10 2020-06-17 Oyagen, Inc. METHOD FOR TREATING OR INHIBITIONING AN EBOLA VIRUS INFECTION
WO2018092728A1 (ja) * 2016-11-16 2018-05-24 国立研究開発法人国立国際医療研究センター 抗ウイルス活性等の生理活性を有するヌクレオシド誘導体
GEP20237457B (en) 2017-02-01 2023-01-10 Atea Pharmaceuticals Inc Nucleotide hemi-sulfate salt for treatment of hepatitis c virus
WO2019060692A1 (en) 2017-09-21 2019-03-28 Chimerix, Inc. MORPHIC FORMS OF 4-AMINO-7- (3,4-DIHYDROXY-5- (HYDROXYMETHYL) -ETRAHYDROFURAN-2-YL) -2-METHYL-7H-PYRROLO [2,3-D] PYRIMIDINE-5-CARBOXAMIDE AND THEIR USES
CN111194217B (zh) 2017-09-21 2024-01-12 里伯赛恩斯有限责任公司 作为hcv rna复制抑制剂的4’-氟-2’-甲基取代的核苷衍生物
US11040975B2 (en) 2017-12-08 2021-06-22 Merck Sharp & Dohme Corp. Carbocyclic nucleoside reverse transcriptase inhibitors
TW202012001A (zh) 2018-04-10 2020-04-01 美商亞堤製藥公司 C型肝炎病毒(hcv)感染硬化之患者的治療
WO2020045628A1 (ja) * 2018-08-31 2020-03-05 ダイキン工業株式会社 核酸アナログ及び抗ｂ型肝炎ウイルス剤
JP2022525818A (ja) * 2019-03-15 2022-05-19 河南真実生物科技有限公司 ２’－フルオロ－４’－置換ヌクレオシド類似体ｉの結晶形ａ及びその調製方法と応用
WO2021158248A1 (en) 2020-02-04 2021-08-12 Oyagen, Inc. Method for treating coronavirus infections
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
US10874687B1 (en) 2020-02-27 2020-12-29 Atea Pharmaceuticals, Inc. Highly active compounds against COVID-19
TW202200161A (zh) 2020-03-20 2022-01-01 美商基利科學股份有限公司 4’-c-經取代-2-鹵基-2’-去氧腺苷核苷之前藥及其製造與使用方法
US11697666B2 (en) 2021-04-16 2023-07-11 Gilead Sciences, Inc. Methods of preparing carbanucleosides using amides
CN114149475B (zh) * 2021-12-14 2023-07-14 新乡拓新药业股份有限公司 一种合成阿兹夫定的工艺方法

Family Cites Families (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5616702A (en) * 1988-11-15 1997-04-01 Merrell Pharmaceuticals Inc. 2-'-ethenylidene cytidine, uridine and guanosine derivatives
WO1997012033A1 (en) 1995-09-27 1997-04-03 Emory University Recombinant hepatitis c virus rna replicase
US5856085A (en) * 1995-12-01 1999-01-05 The Penn State Research Foundation Compositions and methods of developing oligonucleotides and oligonucleotide analogs having antiviral activity
WO1998050530A2 (en) * 1997-05-09 1998-11-12 Ribozyme Pharmaceuticals, Inc. Enzymatic nucleic acids: synthesis, selection and use
DE60005502T2 (de) * 1999-05-12 2004-06-24 Yamasa Corp., Choshi 4'-c-ethynyl-purin-nukleoside
CN100457118C (zh) * 2000-04-13 2009-02-04 法玛塞特有限公司 用于治疗肝炎病毒感染的3′-或2′-羟甲基取代的核苷衍生物
PT1411954E (pt) * 2000-10-18 2011-03-16 Pharmasset Inc Nucleosídeos modificados para o tratamento de infecções virais e proliferação celular anormal
MY134070A (en) 2001-01-22 2007-11-30 Isis Pharmaceuticals Inc Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase
GB0114286D0 (en) * 2001-06-12 2001-08-01 Hoffmann La Roche Nucleoside Derivatives
EP1551421A2 (en) * 2002-06-21 2005-07-13 Merck & Co. Inc. Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase
US7094768B2 (en) * 2002-09-30 2006-08-22 Genelabs Technologies, Inc. Nucleoside derivatives for treating hepatitis C virus infection
KR20060123707A (ko) * 2003-08-27 2006-12-04 바이오타, 인코포레이티드 치료제로서의 신규 트리시클릭 뉴클레오시드 또는뉴클레오티드
US20070265222A1 (en) 2004-06-24 2007-11-15 Maccoss Malcolm Nucleoside Aryl Phosphoramidates for the Treatment of Rna-Dependent Rna Viral Infection
JP2008523098A (ja) * 2004-12-10 2008-07-03 エモリー・ユニバーシテイ ウィルス感染および異常細胞増殖の治療用の２′および３′−置換シクロブチルヌクレオシド類縁体
AU2006294807B2 (en) 2005-09-26 2013-01-17 Gilead Pharmasset Llc Modified 4'-nucleosides as antiviral agents
EP2361922B1 (en) * 2006-10-10 2012-08-22 Janssen Products, L.P. Intermediate to HCV-Nucleoside Inhibitors
DE102006061756A1 (de) 2006-12-28 2008-07-03 Alfred Kärcher Gmbh & Co. Kg Radialgebläse und mit einem Radialgebläse versehenes Hochdruck-Reinigungsgerät
US7964580B2 (en) 2007-03-30 2011-06-21 Pharmasset, Inc. Nucleoside phosphoramidate prodrugs
CN100532388C (zh) 2007-07-16 2009-08-26 郑州大学 2’-氟-4’-取代-核苷类似物、其制备方法及应用
KR101546712B1 (ko) 2007-11-20 2015-08-24 얀센 파마슈티카 엔.브이. 히스타민 ｈ3 수용체의 조절제로서 사이클로알킬옥시- 및 헤테로사이클로알킬옥시피리딘 화합물
US20090318380A1 (en) 2007-11-20 2009-12-24 Pharmasset, Inc. 2',4'-substituted nucleosides as antiviral agents
CN101868456B (zh) 2007-11-20 2012-07-25 住友化学株式会社 吡啶化合物、杀虫组合物和用于控制害虫的方法

Also Published As

Publication number Publication date
EP2631239A1 (en) 2013-08-28
EP2848624B1 (en) 2020-03-25
US9676808B2 (en) 2017-06-13
JP5492785B2 (ja) 2014-05-14
PE20091424A1 (es) 2009-09-24
HK1149017A1 (en) 2011-09-23
US20140235563A1 (en) 2014-08-21
US20120232029A1 (en) 2012-09-13
EP2227482A1 (en) 2010-09-15
US8765710B2 (en) 2014-07-01
PL2227482T3 (pl) 2018-05-30
PT2631239E (pt) 2015-04-27
ES2534442T3 (es) 2015-04-23
AU2008326569A1 (en) 2009-05-28
NZ601486A (en) 2013-11-29
CN101932590A (zh) 2010-12-29
PT2227482T (pt) 2018-03-21
ES2794025T3 (es) 2020-11-17
US20090318380A1 (en) 2009-12-24
AR069634A1 (es) 2010-02-10
CA2706327C (en) 2018-10-02
IL205895A0 (en) 2010-11-30
EP2848624A1 (en) 2015-03-18
CA2706327A1 (en) 2009-05-28
US20160280735A1 (en) 2016-09-29
US9296777B2 (en) 2016-03-29
ES2663086T3 (es) 2018-04-11
CL2008003431A1 (es) 2009-11-27
AU2008326569B2 (en) 2014-01-09
UY31476A1 (es) 2009-07-17
HK1208468A1 (en) 2016-03-04
EP2227482B1 (en) 2018-01-10
CN101932590B (zh) 2015-04-15
TW200936603A (en) 2009-09-01
WO2009067409A1 (en) 2009-05-28
EP2631239B1 (en) 2015-01-07
NO2227482T3 (sl) 2018-06-09
PA8804701A1 (es) 2009-07-23
JP2011503234A (ja) 2011-01-27

Similar Documents

Publication Publication Date Title
SI2227482T1 (sl) 2',4'-substituirani nukleozidi kot antivirusna sredstva
HRP20200214T1 (hr) Sulfoniluree i srodni spojevi i njihova uporaba
PL409123A1 (pl) Związki, ich zastosowanie i kompozycje do leczenia wirusowego zapalenia wątroby typu C
US9655898B2 (en) Pharmaceutical compositions containing pemetrexed having extended storage stability
JP2008523098A5 (sl)
RU2006109491A (ru) Новые трициклические нуклеозиды или нуклеотиды в качестве терапевтических средств
HRP20210027T1 (hr) Ciklički dinukleotidni spojevi
CA2490191A1 (en) Modified 2' and 3' -nucleoside prodrugs for treating flaviviridae infections
ES2381672T3 (es) Preparación en solución acuosa que comprende un antibiótico aminoglicósido y bromfenaco
KR930702371A (ko) 뉴클레오시드 유도체
RU95118285A (ru) N-алкил-2-замещенные атф и его аналоги
PE20060837A1 (es) COMPUESTOS DE 3H-OXAZOLO Y 3H-TIAZOLO[4,5-d]PIRIMIDIN-2-ONA 3,5-DISUSTITUIDA Y 3,5,7-TRISUSTITUIDA Y PROFARMACOS DE LOS MISMOS
RU2004110719A (ru) Зздабиторы протеаз, расщепляющих за пролином
EA200900358A1 (ru) Энантиомерно чистые фосфоиндолы в качестве ингибиторов hiv
HRP20211762T1 (hr) Derivati benzoksaborola za liječenje bakterijskih infekcija
JP2006524711A5 (sl)
SI3106463T1 (sl) Spojine substituiranega pirazolo(1,5-)pirimidina kot inhibitorji TRK kinaze
JP2008509166A5 (sl)
EA200500511A1 (ru) Производные бензодиазепина, содержащие их продукт и фармацевтическая композиция и их применение
HRP20120478T1 (hr) Formulacije koje sadrže spojeve srodne jorumicinu renieramicinu safracinu ili saframicinu i disaharid za liječenje proliferativnih oboljenja
JP2008522981A5 (sl)
DE69334348D1 (de) Enantiomerisch reine Beta-D-Dioxolan-Nukleoside
BR0111569A (pt) Agentes antivirais de imidazopiridina e imidazopirimidina
JP2008514639A5 (sl)
JP2013500977A5 (sl)