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Successful kinase bypass with new acyclovir phosphoramidate prodrugs. 2008

Christopher McGuigan, and Marco Derudas, and Joachim J Bugert, and Graciela Andrei, and Robert Snoeck, and Jan Balzarini
Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff CF10 3NB, UK. mcguigan@cardiff.ac.uk

Novel phosphoramidates of acyclovir have been prepared and evaluated in vitro against acyclovir-sensitive and -resistant herpes simplex virus (HSV) types 1 and 2 and varicella-zoster virus (VZV). Unlike the parent nucleoside these novel phosphate prodrugs retain antiviral potency versus the ACV-resistant virus strain, suggesting an efficient bypass of the viral thymidine kinase.

UI MeSH Term Description Entries
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
D011355 Prodrugs A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug. Drug Precursor,Drug Precursors,Pro-Drug,Prodrug,Pro-Drugs,Precursor, Drug,Precursors, Drug,Pro Drug,Pro Drugs
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000212 Acyclovir A GUANOSINE analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes. Acycloguanosine,9-((2-Hydroxyethoxy)methyl)guanine,Aci-Sanorania,Acic,Aciclobeta,Aciclostad,Aciclovir,Aciclovir Alonga,Aciclovir-Sanorania,Acifur,Acipen Solutab,Acivir,Activir,Acyclo-V,Acyclovir Sodium,Antiherpes Creme,Avirax,Cicloferon,Clonorax,Cusiviral,Genvir,Herpetad,Herpofug,Herpotern,Herpoviric,Isavir,Laciken,Mapox,Maynar,Milavir,Opthavir,Supraviran,Viclovir,Vipral,Virax-Puren,Virherpes,Virmen,Virolex,Virupos,Virzin,Wellcome-248U,Zoliparin,Zovirax,Zyclir,aciclovir von ct,Aci Sanorania,Aciclovir Sanorania,Acyclo V,Alonga, Aciclovir,Sodium, Acyclovir,Solutab, Acipen,Virax Puren,ViraxPuren,Wellcome 248U,Wellcome248U
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
D013937 Thymidine Kinase An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21. Deoxythymidine Kinase,Deoxypyrimidine Kinase,Kinase, Deoxypyrimidine,Kinase, Deoxythymidine,Kinase, Thymidine
D014645 Herpesvirus 3, Human The type species of VARICELLOVIRUS causing CHICKENPOX (varicella) and HERPES ZOSTER (shingles) in humans. Chickenpox Virus,Herpes zoster Virus,Ocular Herpes zoster Virus,VZ Virus,Varicella-Zoster Virus,HHV-3,Herpesvirus 3 (alpha), Human,Herpesvirus Varicellae,Human Herpesvirus 3,Chickenpox Viruses,Herpes zoster Viruses,VZ Viruses,Varicella Zoster Virus,Varicella-Zoster Viruses,Varicellae, Herpesvirus
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
D018258 Herpesvirus 2, Human A species of SIMPLEXVIRUS associated with genital infections (HERPES GENITALIS). It is transmitted by sexual intercourse and close personal contact. HSV-2,Herpes Simplex Virus 2,Human Herpesvirus 2,HHV-2,Herpes Simplex Virus Type 2,Herpesvirus 2 (alpha), Human

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