title: Tricyclic theophylline derivatives with high water-solubility: structure-activity relationships at adenosine receptors, phosphodiesterases, and benzodiazepine binding sites.
abstract: A series of tricyclic, highly water-soluble theophylline derivatives (pyrimido[2,1-f]-theophyllines) containing a basic side chain was investigated in rat brain A1- and A2 adenosine receptor binding assays, phosphodiesterase assays, and benzodiazepine binding studies. Among the new compounds adenosine receptor antagonists with affinities in the same range as the parent compound theophylline were identified. In addition, some compounds were selective for the A1 adenosine receptor subtype. The compounds generally exhibited lower inhibitory activity at brain phosphodiesterases than the parent theophylline. Two compounds were found to show an about 10-fold affinity for benzodiazepine binding sites compared with caffeine and theophylline.
authors.affiliation: Pharmazeutisches Institut, Universität Tübingen, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Geis
authors.forename: B
authors.initials: B
authors.lastname: Grahner
authors.forename: M
authors.initials: M
authors.lastname: Pawłowski
authors.forename: A
authors.initials: A
authors.lastname: Drabczynska
authors.forename: M
authors.initials: M
authors.lastname: Gorczyca
authors.forename: C E
authors.initials: CE
authors.lastname: Müller
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D006160:Guanosine Triphosphate / Q000378:metabolism; D066298:In Vitro Techniques; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D010660:Phenylisopropyladenosine / Q000493:pharmacokinetics; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000187:drug effects*; D012995:Solubility; D013329:Structure-Activity Relationship; D013806:Theophylline / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D058787:GABA-A Receptor Antagonists; D010726:Phosphodiesterase Inhibitors; D018047:Receptors, Purinergic P1; D010660:Phenylisopropyladenosine; D002110:Caffeine; D006160:Guanosine Triphosphate; D013806:Theophylline