Benzodiazepine Receptor Binding Activity of 9-(1-Phenylethyl)purines

Article abstract of DOI:10.1021/jm00169a013

Several α-methyl analogues of the 9-benzylpurines that bind to the benzodiazepine receptor (BZR) were synthesized and tested for BZR-binding activity.Although introduction of a m-amino group and an 8-bromo substituent gave an additive increase in BZR affinity with 9-(3-aminobenzyl)-8-bromo-6-(dimethylamino)-9H-purine (4), addition of an α-methyl group to 4 resulted in loss in BZR affinity.This loss in affinity is apparently due to repulsive, steric interactions between the 8-bromo and 9-(1-phenylethyl) substituents, which results in a conformation that is not optimal for interaction with the BZR.Several compounds were tested on a modified Geller-Seifter conflict schedule, but none exhibited significant anxiolytic activity.