BIOMAT Database Logo BIOMAT Database Logo

Phosphoramidate protides of 2',3'-dideoxy-3'-fluoroadenosine and related nucleosides with potent activity against HIV and HBV. 2003

Kristjan S Gudmundsson, and Susan M Daluge, and Lance C Johnson, and Robert Jansen, and Richard Hazen, and Lynn D Condreay, and Christopher McGuigan
Division of Chemistry, GlaxoSmithKline, Research Triangle Park, North Carolina 27709, USA. Kristjan.S.Gudmundsson@gsk.com

Syntheses of phosphoramidate protides of several 2',3'-dideoxy-3'-fluoroadenosine derivatives by treatment of the nucleoside with phosphorochloridates in the presence of pyridine and t-BuMgCl is described. Several of these protides showed significantly improved antiviral potency over the parent nucleoside against HIV and HBV. Especially marked was the improvement in potency of phosphoramidate protides of 2',3'-dideoxy-3'-fluoroadenosine against both HIV and HBV.

UI MeSH Term Description Entries
D008214 Lymphocytes White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS. Lymphoid Cells,Cell, Lymphoid,Cells, Lymphoid,Lymphocyte,Lymphoid Cell
D010756 Phosphoric Acids Inorganic derivatives of phosphoric acid (H3PO4). Note that organic derivatives of phosphoric acids are listed under ORGANOPHOSPHATES. Pyrophosphoric Acids,Acids, Phosphoric,Acids, Pyrophosphoric
D003839 Deoxyadenosines Adenosine molecules which can be substituted in any position, but are lacking one hydroxyl group in the ribose part of the molecule. Adenine Deoxyribonucleosides,Adenylyldeoxyribonucleosides,Deoxyadenosine Derivatives,Deoxyribonucleosides, Adenine,Derivatives, Deoxyadenosine
D006515 Hepatitis B virus The type species of the genus ORTHOHEPADNAVIRUS which causes human HEPATITIS B and is also apparently a causal agent in human HEPATOCELLULAR CARCINOMA. The Dane particle is an intact hepatitis virion, named after its discoverer. Non-infectious spherical and tubular particles are also seen in the serum. Dane Particle,Hepatitis Virus, Homologous Serum,B virus, Hepatitis,Hepatitis B viruses,Particle, Dane,viruses, Hepatitis B
D006678 HIV Human immunodeficiency virus. A non-taxonomic and historical term referring to any of two species, specifically HIV-1 and/or HIV-2. Prior to 1986, this was called human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). From 1986-1990, it was an official species called HIV. Since 1991, HIV was no longer considered an official species name; the two species were designated HIV-1 and HIV-2. AIDS Virus,HTLV-III,Human Immunodeficiency Viruses,Human T-Cell Lymphotropic Virus Type III,Human T-Lymphotropic Virus Type III,LAV-HTLV-III,Lymphadenopathy-Associated Virus,Acquired Immune Deficiency Syndrome Virus,Acquired Immunodeficiency Syndrome Virus,Human Immunodeficiency Virus,Human T Cell Lymphotropic Virus Type III,Human T Lymphotropic Virus Type III,Human T-Cell Leukemia Virus Type III,Immunodeficiency Virus, Human,Immunodeficiency Viruses, Human,Virus, Human Immunodeficiency,Viruses, Human Immunodeficiency,AIDS Viruses,Human T Cell Leukemia Virus Type III,Lymphadenopathy Associated Virus,Lymphadenopathy-Associated Viruses,Virus, AIDS,Virus, Lymphadenopathy-Associated,Viruses, AIDS,Viruses, Lymphadenopathy-Associated
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000577 Amides Organic compounds containing the -CO-NH2 radical. Amides are derived from acids by replacement of -OH by -NH2 or from ammonia by the replacement of H by an acyl group. (From Grant & Hackh's Chemical Dictionary, 5th ed) Amide
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D015394 Molecular Structure The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. Structure, Molecular,Molecular Structures,Structures, Molecular
D016048 Dideoxyadenosine A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is an inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal side effect is nephrotoxicity. In vivo, dideoxyadenosine is rapidly metabolized to DIDANOSINE (ddI) by enzymatic deamination; ddI is then converted to dideoxyinosine monophosphate and ultimately to dideoxyadenosine triphosphate, the putative active metabolite. 2',3'-Dideoxyadenosine,ddA (Antiviral),2',3' Dideoxyadenosine

Related Publications

Kristjan S Gudmundsson, and Susan M Daluge, and Lance C Johnson, and Robert Jansen, and Richard Hazen, and Lynn D Condreay, and Christopher McGuigan
Synthesis and HIV inhibition activity of 2',3'-dideoxy-3'-C-hydroxymethyl nucleosides.
December 1996, Journal of medicinal chemistry,
Kristjan S Gudmundsson, and Susan M Daluge, and Lance C Johnson, and Robert Jansen, and Richard Hazen, and Lynn D Condreay, and Christopher McGuigan
Synthesis and anti-HIV activity of carbocyclic 2',3'-didehydro-2',3'-dideoxy 2,6-disubstituted purine nucleosides.
January 1990, Journal of medicinal chemistry,
Kristjan S Gudmundsson, and Susan M Daluge, and Lance C Johnson, and Robert Jansen, and Richard Hazen, and Lynn D Condreay, and Christopher McGuigan
Synthesis of 2',5'-dideoxy-2-fluoroadenosine and 2',5'-dideoxy-2,5'-difluoroadenosine: potent P-site inhibitors of adenylyl cyclase.
February 2004, Journal of medicinal chemistry,
Kristjan S Gudmundsson, and Susan M Daluge, and Lance C Johnson, and Robert Jansen, and Richard Hazen, and Lynn D Condreay, and Christopher McGuigan
Synthesis and anti-herpetic activity of phosphoramidate ProTides.
June 2013, ChemMedChem,
Kristjan S Gudmundsson, and Susan M Daluge, and Lance C Johnson, and Robert Jansen, and Richard Hazen, and Lynn D Condreay, and Christopher McGuigan
Synthesis and potent anti-HIV activity of L-2',3'-didehydro-2',3'-dideoxy-2'-fluoro-4'-thiocytidine.
January 2002, Organic letters,
Kristjan S Gudmundsson, and Susan M Daluge, and Lance C Johnson, and Robert Jansen, and Richard Hazen, and Lynn D Condreay, and Christopher McGuigan
D- and L-2',3'-didehydro-2',3'-dideoxy-3'-fluoro-carbocyclic nucleosides: synthesis, anti-HIV activity and mechanism of resistance.
April 2007, Journal of medicinal chemistry,
Kristjan S Gudmundsson, and Susan M Daluge, and Lance C Johnson, and Robert Jansen, and Richard Hazen, and Lynn D Condreay, and Christopher McGuigan
Synthesis of 3'-amino-2',3'-dideoxy-hexofuranose nucleosides with potential anti-viral activity.
February 1991, Archiv der Pharmazie,
Kristjan S Gudmundsson, and Susan M Daluge, and Lance C Johnson, and Robert Jansen, and Richard Hazen, and Lynn D Condreay, and Christopher McGuigan
Synthesis and biological evaluation of 2',3'-dideoxy-L-pyrimidine nucleosides as potential antiviral agents against human immunodeficiency virus (HIV) and hepatitis B virus (HBV).
March 1994, Journal of medicinal chemistry,
Kristjan S Gudmundsson, and Susan M Daluge, and Lance C Johnson, and Robert Jansen, and Richard Hazen, and Lynn D Condreay, and Christopher McGuigan
Pronucleotides of 2',3'-Dideoxy-2',3'-Didehydrothymidine as Potent Anti-HIV Compounds.
September 2023, Journal of medicinal chemistry,
Kristjan S Gudmundsson, and Susan M Daluge, and Lance C Johnson, and Robert Jansen, and Richard Hazen, and Lynn D Condreay, and Christopher McGuigan
Synthesis and antiviral activity of purine 2',3'-dideoxy-2',3'-difluoro-D-arabinofuranosyl nucleosides.
May 2009, Nucleosides, nucleotides & nucleic acids,
Copied contents to your clipboard!