Patent Evaluation: Novel Quinolines as Acetylcholine Receptor Agonists

Summary

Novelty: N-Substituted-2-aminoquinolines are disclosed which are said to exhibit acetylcholine receptor (mAChR) agonist activity and show selectivity for the M₁ receptor subtype. These compounds are potentially useful for amelioration of the cholinergic deficits associated with Alzheimer's disease and other dementias.

Biology: Competition binding experiments, which were conducted in rat cerebral cortex membranes against the M₁ selective antagonists pirenzepine (and the M₂ selective quinuclidinyl benzylate), showed IC₅₀ values of between 0.21-50 μM, with M₂/M₁ ratios in the range 10-90. The compounds were able to reverse scopolamine-induced hyperactivity and memory deficits at doses of 30-45 mg/kg ip.

Chemistry: Synthesis of the compounds employs conventional methods and are exemplified in thirteen cases. A preferred example of the claim is 4-methyl-N-[3-(4-morpholinyl)-propyl]-2-quinolinamine.

Structure: