Patent Evaluation: Dual Muscarinic Agonists/Acetylcholinesterase Inhibitors

Summary

Novelty: Novel derivatives of 3-aryl-1,2,4-triazines and processes for their preparation are disclosed. The compounds bind significantly to sigma, M₁, A₁, and A₂ receptors and are claimed to be acetylcholinesterase (AChE) inhibitors. They are said to be useful as analgesics and as such are potential useful for the treatment of a variety of CNS disoders, including depression and cognitive dysfunction.

Biology: Analgesic activity was assessed from the ability of the compounds to inhibit acetic acid-induced writhing in mice. For certain (unspecified) compounds ED₅₀ values of 25 mg/kg ip were observed. Compounds (again unspecified) inhibited acetylcholinesterase with IC₅₀ values in the order of 10⁻⁷M, and bound to sigma, M₁, A₁, and A₂ receptors with ED₅₀ values in the order of 10⁻⁶M. No specfic results are disclosed.

Chemistry: Eighty compounds are exemplified by synthesis. 5-Benzyl-3-phenyl-6-(piperidinoethylamino)-1,2,4-triazine is one of four specifically claimed compounds.

Structure: