Synthesis and evaluation of a series of 2'-O-acyl derivatives of 9-beta-D-arabinofuranosyladenine as antiherpes agents.
A series of four 9-(2-O-acyl-beta-D-arabinofuranosyl)adenines (5a-d) was synthesized by acylation of 9-[3,5-bis-O-(tert-butyldimethylsilyl)-beta-D-arabinofuranosyl]adenine (2), followed by removal of the tert-butyldimethylsilyl groups under conditions (HOAc, tetra-n-butylammonium fluoride) that prevented acyl migration. The four 2'-O-acyl derivatives 5a-d showed activity in vitro against herpes type 1 viruses [virus ratings = 1.5-2.6; MIC50 = 26-72 micrograms/mL (8.48-21.3 X 10(-5) M)]. The 2'-O-acetyl (5a) and 2'-O-valeryl (5d) derivatives were evaluated in a guinea pig model for genital herpes (herpes type 2); only 5a showed potent activity when given 6 or 24 h postinfection.
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis*; D005260:Female; D006168:Guinea Pigs; D006558:Herpes Genitalis / Q000188:drug therapy; D006566:Herpesviridae Infections / Q000188:drug therapy*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018139:Simplexvirus / Q000187:drug effects; D012995:Solubility; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000998:Antiviral Agents; D014740:Vidarabine