Synthesis, conformational analysis and antiviral and antitumoral activity of new 1,2-disubstituted carbocyclic nucleosides.
New 1',2'-cis-disubstituted 8-azapurine-based carbocyclic analogues of nucleosides with or without a methylene between the carbocycle and the base were synthesised, starting from appropriate amino alcohols, via 6-chloro-8-azapurines; their antiviral and antitumoral activities were evaluated; and their structures were compared with that of 2',3'-dideoxyadenosine (ddA) on the basis of AM1 calculations. No new compound had antiviral activity. The one with the best overall antitumoral activity against L1210, Molt4/C8 and CEM/0 cells, compound 10, was that in which the position of the hydroxymethyl group on the carbocycle relative to the heterocyclic base was closest to that found in the best-fitting low-energy conformer of ddA.
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D016048:Dideoxyadenosine / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D009705:Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014780:Viruses / Q000187:drug effects
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D009705:Nucleosides; D016048:Dideoxyadenosine