Patent Evaluation: Adenosine derivatives as selective adenosine receptor agonists

Summary

Novelty: A series of 6-hydrazino-substituted adenosine derivatives are claimed. These compounds act as selective A₁ adenosine receptor agonists and may be useful in treating a number of CNS disorders including, anoxia, traumatic injury, ischaemia, migraine and neurodegen-erative diseases.

Biology: Binding data are given for four compounds, both for A₁ and A₂ binding. Also in vivo data are given in a DMCM-induced seizure model in mice, in which the dose is given ip 2-Chloro-N-(4-phenoxy-1-piperidinyl]adenosine was the most potent and selective compound with a K_i value for A₁ of 1.4nM, A₂ of 1,200nM and an ED₅₀ value of 0.9mg/kg.

Chemistry: The compounds can be prepared from the 6-halo or TMS-0-adenosine derivatives by displacement with a hydrozine derivative. Twenty-three examples are given but no compounds are named within the claims.