title: Benzodiazepine receptor binding activity of 8-substituted-9-(3-substituted-benzyl)-6-(dimethylamino)-9H-purines.
abstract: A series of 8-substituted analogues of 9-(3-aminobenzyl)-6-(dimethylamino)-9H-purine (8) were synthesized and tested for their ability to bind to the benzodiazepine receptor (BZR) in rat brain tissue. The most active compound was the 8-bromo-9-(3-formamidobenzyl) analogue 16 (IC50 = 0.011 microM), which was 1000-fold more active than the parent 9-benzyl-6-(dimethylamino)-9H-purine (1) and nearly as active as diazepam. Although substitution of a m-formamido group and an 8-bromo substituent on 1 imparted potent BZR binding activity, neither 16 nor 11 analogues exhibited significant anxiolytic activity on a modified Geller-Seifter conflict schedule.
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: J A
authors.initials: JA
authors.lastname: Linn
authors.forename: M P
authors.initials: MP
authors.lastname: Krochmal
authors.forename: R M
authors.initials: RM
authors.lastname: Ferris
authors.forename: J L
authors.initials: JL
authors.lastname: Howard
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D003220:Conflict, Psychological; D003975:Diazepam / Q000378:metabolism; D015394:Molecular Structure; D011687:Purines / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D014151:Anti-Anxiety Agents; D011687:Purines; D011963:Receptors, GABA-A; C062442:8-bromo-6-(dimethylamino)-9-(3-formamidobenzyl)-9H-purine; D003975:Diazepam