title: Benzodiazepine receptor binding activity of 6,9-disubstituted purines.
abstract: 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.
authors.affiliation: Division of Organic Chemistry, Burroughs Wellcome Co., Research Triangle Park, North Carolina 27709.
authors.forename: J L
authors.initials: JL
authors.lastname: Kelley
authors.forename: E W
authors.initials: EW
authors.lastname: McLean
authors.forename: R M
authors.initials: RM
authors.lastname: Ferris
authors.forename: J L
authors.initials: JL
authors.lastname: Howard
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D003220:Conflict, Psychological; D003975:Diazepam / Q000378:metabolism; D005260:Female; D011687:Purines / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000927:Anticonvulsants; D011687:Purines; D011963:Receptors, GABA-A; D003975:Diazepam