Design, synthesis and biological activity evaluation of adenosine analogues

N⁶-(2-Hydroxyethyl) adenosine, HEA (1), an active ingredient isolated from cultured mycelia of cordyceps species which is a famous traditional tonic in China, showed brain protective, sedative hypnotic activity in pharmacological tests.  In order to explore novel non-benzodiazepine sedative-hypnotic agents, HEA was treated as the lead compound.  Twenty three target compounds were designed and synthesized.  Their chemical structures were characterized by ¹H NMR, MS and elemental analysis.  Pharmacological test in vivo showed that target compounds 8, 4, 13 were more active than HEA on locomotor and gasping activities of mice.  Structure-activity relationships showed that the ribose moiety at N-9 position of adenine base was critical for activity.