Patent Evaluation: Azabicycles as ACh Agonists

Summary

Novelty: Oxadiazole and thiadiazole azabicyclic derivatives are claimed along with their use for the treatment of Alzheimer's disease, severe pain and glaucoma.

Biology: Binding data are given for sixty-eight examples which show a range of activity against ³H-oxo-M. The IC₅₀ activity of most compounds falls into the range 0.3–10 ng/ml; the specified compound had an IC₅₀ = 0.3 ng/ml.

Chemistry: All sixty-eight examples are named within the claims with the most common azabicycles being azabicyclo[2.2.2]octane or azabicyclo[2.2.1]heptane. The most active compound is 3-(3-propylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo[2.2.2]octane oxalate.

Structure: