Patent Evaluation: Adenosine Agonists as Antiarrhythmic Agents

Summary

Novelty: The use of known adenosine derivatives and a novel 2′-O-alkyl adenosine derivative is disclosed for the treatment of neurodegenerative disorders, peripheral neuropathies, diabetes, arrhythmias etc. The compounds are claimed to possess adenosine-1-agonist, renin inhibitory, lipid lowering and antithrombotic activities.

Biology: Selected compounds have been evaluated for their affinity for adenosine receptors (A₁ and A₂). Cyclopentyl adenosine is said to show potent receptor binding (K_D = 0.74 nM) and to be a highly selective displacer of binding to A₁ receptors (ratio A1:A2=1260). 2-Phenylaminoadenosine is said to be a relatively weak but selective A₂ receptor ligand (K_D = 2460 nM ratio A1:A2 = 0.1). Data are also presented for their antiarrhythmic, vasodilating, blood flow promoting through ischaemic skeletal muscle, glucose transport in rat adipocytes and for protection against infarction by preconditioning.

Chemistry: 6-Cyclohexyl-2′-O-methyladenosine 1-5 hydrate is specifically claimed.

Structure: