Synthesis and biological activity of 9-(2,6-difluorobenzyl)-9H-purines bearing chlorine

Mitsunobu reaction of 2,6-dichloropurine with 2,6-difluorobenzyl alcohol ga ve 2,6-dichloro-9-(2,6-difluorobenzyl)-9H-purine and 7-benzylated congener in 73% and 10% yield, respectively. Treatment of the former compound with a mmonia gave 2-chloro-9-(2,6-difluorobenzyl)adenine (1) in good yield. Also, 2-amino-6-chloro-purine was condensed with 2,6-difluorobenzyl alcohol in a similar manner to afford 2-amino-6-chloro-9-(2,6-difluorobenzyl)-9H-purine (2) as a major product. Inhibition of phosphodiesterase (PDE) isozymes by 9-(2,6-difluorobenzyl)-9H-purines was investigated and both 1 and 2 were fo und to he good inhibitors of PDE2 in addition to PDE4.