Novel 6-azapyrimidine-2'-deoxy-4'-thionucleosides: synthesis, biological evaluation and conformational analysis.
We report the synthesis of novel 1-(2'-deoxy-4'-thio-beta-D-erythro-pentofuranosyl)-(6-azapyrimidine) nucleosides and the subsequent preparation of a series of N3-substituted analogues. All the novel compounds were evaluated against a range of viruses, however they lacked any measurable activity. The lack of anti-herpetic activity may be a result of the parent nucleoside having poor affinity for herpes simplex virus type 1 thymidine kinase. Conformational analysis of the parent nucleoside showed a twist (3T2) sugar conformation commonly displayed by 2'-deoxy-4'-thionucleosides and the anti-human immunodeficiency virus type 1 agents zidovudine and 3'-fluoro-ddT.
Inguaggiato
G
G
Medicinal Chemistry Division, Welsh School of Pharmacy, Cardiff University, UK.
Hughes
D
D
De Clercq
E
E
Balzarini
J
J
Simons
C
C
D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D018360:Crystallography, X-Ray; D015658:HIV Infections; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013872:Thionucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors; D014709:Vero Cells
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D011741:Pyrimidine Nucleosides; D013872:Thionucleosides; D013937:Thymidine Kinase; D054303:HIV Reverse Transcriptase