Ishihara_1993_Chem.Pharm.Bull.(Tokyo)_41_529

Inhibitors of acetylcholinesterase (AChE) have been designed based on a working hypothesis of the enzyme's active site. These compounds were tested for their inhibitory activities on AChE and omega-[N-ethyl-N-(phenylmethyl)amino]-1-phenyl-1-alkanones (3) were found to be potent inhibitors. Various analogues of 3 were prepared to study the effect on AChE inhibition of partial restriction of conformation. Compounds with potent AChE inhibition were further evaluated in terms of central selectivity: the ratio of central action (ameliorating effect on scopolamine-induced memory impairment using a T-maze alternation task) to peripheral action.