Synthesis and muscarinic activity of novel aniline derivatives with a 1-azabicyclo[3.3.0]octane moiety.

In order to develop drugs effective against Alzheimer's disease, we synthesized a series of aniline derivatives having a characteristic cyclic amine, 1-azabicyclo[3.3.0]octane ring, and evaluated their binding affinity for the central muscarinic cholinergic receptor. Among these compounds which showed high affinity to the M1 receptor, N-[2-(1-Azabicyclo[3.3.0]octan-5-yl)ethyl]-2-nitroaniline (9f fumarate, SK-946) showed the highest affinity. The ability of this compound to improve cognitive function was assessed using the passive avoidance test in scopolamine-induced dementia mice. Some anilines with a 1-azabicyclo[3.3.1]nonane ring were also synthesized by the ring expansion of the 1-azabicyclo[3.3.0]octane ring, and showed a high affinity for the central muscarinic cholinergic receptor.