Synthesis and biological evaluation of acyclic neplanocin analogues.
Acyclic neplanocin analogues were prepared by condensation of adenine or N2-acetylguanine with (E)-1,4-dichlorobut-2-ene and subsequent hydrolysis. The N-9-substituted product 9-[(E)-4-hydroxybut-2-enyl]adenine was obtained when adenine was employed as the starting purine, while N2-acetylguanine yielded both the N-7 and N-9 isomers. Cell-culture studies revealed that only the chloro-substituted intermediate 9-[(E)-4-chlorobut-2-enyl]adenine exhibited significant cytotoxicity against P-388 mouse lymphoid leukemia cells, while the N-9-substituted guanine analogue 9-[(E)-4-hydroxybut-2-enyl]guanine inhibited replication of herpes simplex viruses type 1 and type 2.
D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D000998:Antiviral Agents / Q000138:chemical synthesis*; D004353:Drug Evaluation, Preclinical; D006147:Guanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D007202:Indicators and Reagents; D007941:Leukemia P388 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D018139:Simplexvirus / Q000187:drug effects; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D007202:Indicators and Reagents; D006147:Guanine; D000225:Adenine