Benzodiazepine receptor binding activity of 6,9-disubstituted purines

A series of 6,9-disubstituted purines were tested for their ability to bind to the benzodiazepine receptor in rat brain tissue. One of the most active compounds was 9-(3-aminobenzyl)-6-(dimethylamino)-9H-purine (44) with an IC50 = 0.9 microM, which was only 4.5-fold higher than the IC50 for chlordiazepoxide. Substitution of a 3-aminobenzyl or 3-hydroxybenzyl group at the 9-position of 6-(dimethylamino)purine led to over a 50-fold increase in receptor affinity. Compound 44 did not exhibit significant anxiolytic activity, nor did anticonvulsant activity correlate with relative receptor binding affinity.