Central cholinergic agents. IV. Synthesis and acetylcholinesterase inhibitory activities of omega-[N-ethyl-N-(phenylmethyl)amino]-1-phenyl-1-alkanones and their analogues with partial conformational restriction.
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.
Ishihara
Y
Y
Pharmaceutical Research Laboratories I, Takeda Chemical Industries, Ltd., Osaka, Japan.
Miyamoto
M
M
Nakayama
T
T
Goto
G
G
D000818:Animals; D001596:Benzylamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008568:Memory / Q000187:drug effects*; D011863:Radioimmunoassay; D051381:Rats; D013329:Structure-Activity Relationship; D013619:Tacrine / Q000378:metabolism
D001596:Benzylamines; D002800:Cholinesterase Inhibitors; D007659:Ketones; D013619:Tacrine