title: Xanthines with C8 chiral substituents as potent and selective adenosine A1 antagonists.
abstract: Several 8-substituted 1,3-dipropylxanthines were synthesized, and their receptor binding affinities at adenosine A1 and A2 receptors were measured. When enantiomeric pairs of compounds were examined, the R enantiomers were significantly more potent than the corresponding S enantiomers. The most potent compound at the A1 receptor was (R)-3,7-dihydro-8-(1-methyl-2-phenylethyl)-1,3-dipropyl-1H-purine-2,6-di one (5a; MDL 102,503), whose Ki value at the A1 receptor was 6.9 nM. However, a more selective compound was (R)-3,7-dihydro-8-(1-phenylpropyl)-1,3-dipropyl-1H-purine-2,6-dione (5d; MDL 102,234), which had a Ki value of 23.2 nM at the A1 receptor and an A2/A1 ratio of 153.
authors.affiliation: Marion Merrell Dow Research Institute, Cincinnati, Ohio 45215.
authors.forename: N P
authors.initials: NP
authors.lastname: Peet
authors.forename: N L
authors.initials: NL
authors.lastname: Lentz
authors.forename: M W
authors.initials: MW
authors.lastname: Dudley
authors.forename: A M
authors.initials: AM
authors.lastname: Ogden
authors.forename: D R
authors.initials: DR
authors.lastname: McCarty
authors.forename: M M
authors.initials: MM
authors.lastname: Racke
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014970:Xanthines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014970:Xanthines; C084853:MDL 102234