An evaluation of certain chain-extended analogues of 9-beta-D-arabinofuranosyladenine for antiviral and cardiovascular activity.
Several nucleosides modified and chain extended at the 5'-position have been synthesized as follows: N6-benzamido- 9-(2,3-di-O-benzoyl-beta-D-arabino-pentodialdo-1,4-furanosyl)adenine, O=CHR, a leads to (E)-EtOCOCH=CHR (2) b leads to EtOCOCH2CH2R (3) c leads to H2NCOCH2CH2R (6) d leads to 1-(adenin-9- yl)-1,5,6-trideoxy-beta-D-arabino-hepto-1,4-furanuronamide (8); 3 e leads to ethyl 1-(adenin-9-yl)-1,5,6-trideoxy-beta-D-arabino-hepto-1, 4-furanuronate (5) f leads to 1-(adenin-9-yl)-1, 5,6-trideoxy-beta-D-arabino-hepto-1,4-furanuronic acid (4); 5 g leads to 9-(5,6-dideoxy-beta-D-arabino-hepto-1,4-furanosyl)adenine (7) [where a = EtOCOCH=PPh3; b = H2, Pd/C; c = Me2A1NH2; d = NH3/MeOH; e = NaOEt/EtOH; f = NaOH/MeOH; g = LiA1H4]. Both 7 and 8 show activity against herpes simplex virus type 1. The mechanism for such activity is unknown. Compounds 5 and 8 exhibited weak coronary vasodilation effects in dogs.
D000243:Adenosine Deaminase / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D000998:Antiviral Agents / Q000138:chemical synthesis*; D002417:Cattle; D002460:Cell Line; D003326:Coronary Circulation / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects; D004285:Dogs; D007202:Indicators and Reagents; D007413:Intestinal Mucosa / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D018139:Simplexvirus / Q000187:drug effects; D013053:Spectrophotometry; D013329:Structure-Activity Relationship; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014740:Vidarabine / Q000031:analogs & derivatives*
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D007202:Indicators and Reagents; D000243:Adenosine Deaminase; D014740:Vidarabine