The nature of the adenosine receptor will be studied using adenosine agonists and antagonists modified for selectivity and possible affinity labeling. Adenosine plays a key role in physiological processes and currently no selective A1 or A2 antagonists have as yet been developed. Selective agonists and antagonists for adenosine receptors could have clinical importance in the treatment of asthma, as diurectics, respiratory stimulants and as central depressants or stimulants. The following series of adenosine A1 and A2 agonists and antagonists will be synthesized and evaluated: (a) alkyl substituted xanthines; (b) 8-thienyl substituted xanthines (c) 8- cycloalkyl substituted xanthines; (d) 8-phenylxanthine derivatives -functionalized sulfonamides; (e) thio and dithio xanthines; (f) functionalized 2-arylaminoadenosine derivatives; (g) fluorescent probes for adenosine receptors. The biological evaluation will be carried out in collaboration with the Laboratory of Bioorganic Chemistry, NIADDK, and Nova Pharmaceutical Corp. New products generated in Phase II studies will be further evaluated for possible commercial introduction as research tools to the expanding neuroscience community and evaluated as potential therapeutic agents.
