Synthesis and evaluation of a series of 2'-O-acyl derivatives of 9-.beta.-D-arabinofuranosyladenine as antiherpes agents

Abstract
A series of 4 9-(2-O-acyl-.beta.-D-arabinofuranosyl)adenine was synthesized by acylation of 9-[3,5-bis-O-(tert-butyldimethylsilyl)-.beta.-D-arabinofuranosyl]adenine, followed by removal of the tert-butyldimethylsilyl groups under conditions (HOAc, tetra-n-butylammonium fluoride) that prevented acyl migration. The 4 2''-O-acyl derivatives showed activity in vitro against herpes virus type 1 [virus ratings = 1.5-2.6; MIC50 [median minimum inhibitory concentration] = 26-72 .mu.g/ml (8.48-21.3 .times. 10-5 M)]. The 2''-O-acetyl and 2''-O-valeryl derivatives were evaluated in a guinea pig model for genital herpes (herpes type 2); only the 2''-O-acetyl derivative showed potent activity when given 6 or 24 h postinfection.