BIOMAT Database Logo BIOMAT Database Logo

Synthesis and antiviral activity of novel acyclic nucleosides: discovery of a cyclopropyl nucleoside with potent inhibitory activity against herpesviruses. 1998

T Sekiyama, and S Hatsuya, and Y Tanaka, and M Uchiyama, and N Ono, and S Iwayama, and M Oikawa, and K Suzuki, and M Okunishi, and T Tsuji
Central Research Laboratories, Ajinomoto Company, Inc., 1-1 Suzuki-cho, Kawasaki 210, Japan.

A series of acyclic nucleosides with two hydroxymethyl groups mimicking the 3'- and 5'-hydroxyl groups of the 2'-deoxyribose moiety were prepared and evaluated for their antiherpetic activity. Among those, 9-[[cis-1', 2'-bis(hydroxymethyl)cycloprop-1'-yl]methyl]guanine (3) showed extremely potent antiviral activity against herpes simplex virus type-1 (HSV-1) with good selectivity. Both enantiomers of 3 were synthesized starting from chiral epichlorohydrins, and only one of the enantiomers with 1'S,2'R-configuration (3a) exhibited strong antiherpetic activity (IC50 of 0.020 microg/mL against HSV-1 Tomioka vs 0.81 microg/mL for acyclovir). Enantiomer 3a was also more inhibitory than acyclovir against varicella-zoster virus (VZV) but ineffective against human immunodeficiency virus (HIV). Compound 3a is phosphorylated by HSV-1 thymidine kinase (TK) very efficiently. The relationship between conformation and antiherpetic activity in this series of compounds is discussed.

UI MeSH Term Description Entries
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D010948 Viral Plaque Assay Method for measuring viral infectivity and multiplication in CULTURED CELLS. Clear lysed areas or plaques develop as the VIRAL PARTICLES are released from the infected cells during incubation. With some VIRUSES, the cells are killed by a cytopathic effect; with others, the infected cells are not killed but can be detected by their hemadsorptive ability. Sometimes the plaque cells contain VIRAL ANTIGENS which can be measured by IMMUNOFLUORESCENCE. Bacteriophage Plaque Assay,Assay, Bacteriophage Plaque,Assay, Viral Plaque,Assays, Bacteriophage Plaque,Assays, Viral Plaque,Bacteriophage Plaque Assays,Plaque Assay, Bacteriophage,Plaque Assay, Viral,Plaque Assays, Bacteriophage,Plaque Assays, Viral,Viral Plaque Assays
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004353 Drug Evaluation, Preclinical Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications. Drug Screening,Evaluation Studies, Drug, Pre-Clinical,Drug Evaluation Studies, Preclinical,Drug Evaluations, Preclinical,Evaluation Studies, Drug, Preclinical,Evaluation, Preclinical Drug,Evaluations, Preclinical Drug,Medicinal Plants Testing, Preclinical,Preclinical Drug Evaluation,Preclinical Drug Evaluations,Drug Screenings,Screening, Drug,Screenings, Drug
D006147 Guanine
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
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
D013237 Stereoisomerism The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed) Molecular Stereochemistry,Stereoisomers,Stereochemistry, Molecular,Stereoisomer

Related Publications

T Sekiyama, and S Hatsuya, and Y Tanaka, and M Uchiyama, and N Ono, and S Iwayama, and M Oikawa, and K Suzuki, and M Okunishi, and T Tsuji
Synthesis and antiviral activity of novel methylene cyclopropyl nucleosides.
December 2000, Archives of pharmacal research,
T Sekiyama, and S Hatsuya, and Y Tanaka, and M Uchiyama, and N Ono, and S Iwayama, and M Oikawa, and K Suzuki, and M Okunishi, and T Tsuji
Synthesis and antiviral activity of novel exomethylene cyclopropyl nucleosides.
January 2001, Nucleosides, nucleotides & nucleic acids,
T Sekiyama, and S Hatsuya, and Y Tanaka, and M Uchiyama, and N Ono, and S Iwayama, and M Oikawa, and K Suzuki, and M Okunishi, and T Tsuji
Synthesis and antiviral activity of novel exomethylene cyclopropyl pyrimidine nucleosides.
December 2002, Archives of pharmacal research,
T Sekiyama, and S Hatsuya, and Y Tanaka, and M Uchiyama, and N Ono, and S Iwayama, and M Oikawa, and K Suzuki, and M Okunishi, and T Tsuji
Synthesis and antiviral activity of novel C-methyl branched cyclopropyl nucleosides.
September 2003, Archives of pharmacal research,
T Sekiyama, and S Hatsuya, and Y Tanaka, and M Uchiyama, and N Ono, and S Iwayama, and M Oikawa, and K Suzuki, and M Okunishi, and T Tsuji
Synthesis and antiviral activity of novel trans-2,2-dimethyl cyclopropyl nucleosides.
November 2003, Archives of pharmacal research,
T Sekiyama, and S Hatsuya, and Y Tanaka, and M Uchiyama, and N Ono, and S Iwayama, and M Oikawa, and K Suzuki, and M Okunishi, and T Tsuji
Synthesis and antiviral activity evaluation of some novel acyclic C-nucleosides.
June 2008, Chemical & pharmaceutical bulletin,
T Sekiyama, and S Hatsuya, and Y Tanaka, and M Uchiyama, and N Ono, and S Iwayama, and M Oikawa, and K Suzuki, and M Okunishi, and T Tsuji
Concise synthesis and antiviral activity of novel unsaturated acyclic pyrimidine nucleosides.
January 2005, Nucleosides, nucleotides & nucleic acids,
T Sekiyama, and S Hatsuya, and Y Tanaka, and M Uchiyama, and N Ono, and S Iwayama, and M Oikawa, and K Suzuki, and M Okunishi, and T Tsuji
Synthesis and antiviral evaluation of novel cyclopropyl nucleosides, phosphonate nucleosides and phosphonic acid nucleosides.
September 2006, Archiv der Pharmazie,
T Sekiyama, and S Hatsuya, and Y Tanaka, and M Uchiyama, and N Ono, and S Iwayama, and M Oikawa, and K Suzuki, and M Okunishi, and T Tsuji
Synthesis of novel difluoro-cyclopropyl guanine nucleosides and their phosphonate analogues as potent antiviral agents.
November 2011, Nucleosides, nucleotides & nucleic acids,
T Sekiyama, and S Hatsuya, and Y Tanaka, and M Uchiyama, and N Ono, and S Iwayama, and M Oikawa, and K Suzuki, and M Okunishi, and T Tsuji
Synthesis and antiviral activity of C-fluoro-branched cyclopropyl nucleosides.
April 2007, European journal of medicinal chemistry,
Copied contents to your clipboard!