Patent Evaluation: AICA Riboside Analogues as Potent Adenosine Release Stimulators

Summary

Novelty: Novel analogues of 5-amino-1-β-D-ribofuranosylimidazole-4-carboxamide (AICA riboside) are disclosed. These compounds are potentially useful for increasing extracellular levels of adenosine and may be of value for the treatment of myocardial, cerebral and other ischaemias. The compounds are said to be, in general, more potent than AICA riboside and have increased half-lives, oral bioavailability and blood/brain barrier penetration.

Biology: Details are given for a number of standard ischaemia models. In a rat heart ischaemia model the specified compound increased cardiac adenosine levels by approximately 50%. In the gerbil ischaemia model, pre-treatment with the preferred compound at 500 mg/kg prevented hippocampal damage.

Chemistry: The synthetic details of seventy-nine compounds are provided. 5-Amino-1-β-D-ribofuranosylimidazole-4-N-(benzyl)carboxamide is a specified compound.

Structure: