title: Benzodiazepine receptor binding activity of 9-(1-phenylethyl)purines.
abstract: Several alpha-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 alpha-methyl group to 4 resulted in a 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.
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; D001522:Behavior, Animal / Q000187:drug effects; D001593:Benzyl Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D003220:Conflict, Psychological; D003975:Diazepam / Q000378:metabolism; D007202:Indicators and Reagents; D007700:Kinetics; D015394:Molecular Structure; D011687:Purines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D001593:Benzyl Compounds; D007202:Indicators and Reagents; D011687:Purines; D011963:Receptors, GABA-A; D003975:Diazepam