title: Caffeine analogs: structure-activity relationships at adenosine receptors.
abstract: Caffeine and analogs that contain ethyl, propyl, allyl, propargyl and other substituents in place of methyl at 1-, 3- and 7-positions were antagonists at the two major classes (A1 and A2) of adenosine receptors. Potency at both receptors increased as methyls were replaced with larger substituents. Certain analogs with only one of the three methyl groups of caffeine replaced by larger substituents were somewhat selective for A2 receptors. None of the analogs were particularly selective for A1 receptors. The presence of polar entities in the substituent at the 1- or 7-position was poorly tolerated at adenosine receptors. Activity of caffeine analogs at A1 and A2 adenosine receptors in a variety of systems and cell types is presented and summarized.
authors.affiliation: Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Md.
authors.forename: J W
authors.initials: JW
authors.lastname: Daly
authors.forename: I
authors.initials: I
authors.lastname: Hide
authors.forename: C E
authors.initials: CE
authors.lastname: Müller
authors.forename: M
authors.initials: M
authors.lastname: Shamim
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001792:Blood Platelets / Q000201:enzymology; D001921:Brain / Q000187:drug effects; D002110:Caffeine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D003342:Corpus Striatum / Q000201:enzymology; D000242:Cyclic AMP / Q000378:metabolism; D005347:Fibroblasts; D006168:Guinea Pigs; D006801:Humans; D051381:Rats; D011983:Receptors, Purinergic / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014970:Xanthines / Q000737:chemistry
chemical_list: D011983:Receptors, Purinergic; D014970:Xanthines; D002110:Caffeine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases