Studies on cognitive enhancing agents. II. Antiamnestic and antihypoxic activities of 1-aryl-2-(2-aminoethoxy)ethanols.
A series of 2-(2-aminoethoxy)-1-phenylethanols having a variety of N- and phenyl-substitution patterns as well as 5- and 6-membered heteroaryl counterparts of our prototype compound 1 (2-(2-dimethylaminoethoxy)-1-phenylethanol) have been prepared and evaluated for antiamnestic and antihypoxic activities. Compound 3b, the 3-methylphenyl analogue of 1, proved to be significantly more potent than 1 in reversing electroconvulsive shock-induced amnesia as well as CO2-induced learning-impairment in mice. It exhibited low acute toxicity in mice and afforded a greater brain/serum concentration ratio than 1 after oral administration to rats.
Ono
S
S
Research Laboratories, Toyama Chemical Co., Ltd., Japan.
Yamafuji
T
T
Chaki
H
H
Morita
H
H
Todo
Y
Y
Maekawa
M
M
Kitamura
K
K
Tai
M
M
Narita
H
H
D000647:Amnesia / Q000188:drug therapy* / Q000523:psychology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001812:Blood-Brain Barrier; D003460:Crystallization; D004597:Electroshock; D000431:Ethanol / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D002534:Hypoxia, Brain / Q000188:drug therapy* / Q000523:psychology; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018697:Nootropic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
D018697:Nootropic Agents; D000431:Ethanol