Synthesis of novel N-alkyl carbamates of a-substituted amides of g-hydroxybutyric acid as potential acetylcholinesterase inhibitors.
In a search for new acetylcholinesterase (AChE) inhibitors, derivatives of N-alkyl carbamates of a-substituted N-benzylamides of g-hydroxybutyric acid (GHB) 2(a-d); 3(a-d); 4(a-d) were obtained. Starting from 3-bromo-tetrahydrofuran-2-one, and N-phenylpiperazine 3-(4-phenylpiperazin-1-yl) tetrahydrofuran-2-one (1) was obtained. The aminolysis of lactone 1 with 4-substituted derivatives of benzylamine yielded N-substituted benzylamides of a-(4-phenylpiperazin-1-yl)-g-hydroxy-butyric acid (2-4). The target compounds were prepared by refluxing N-substituted benzyl-amides of a-(4-phenylpiperazinyl-1-)-GHB with ethyl-, i-propyl-, n-propyl- or n-butyl-isocyanate in dry acetonitrile. The inhibitory potency of AChE was evaluated by means of Ellman's in vitro test.
Musiał
Anna
A
Department of Pharmaceutical Chemistry Jagiellonian University Medical College, 9 Medyczna Str., 30-688 Kraków.
Malawska
Barbara
B
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000494:pharmacology; D002219:Carbamates / Q000138:chemical synthesis* / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D004597:Electroshock; D006885:Hydroxybutyrates / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice
D000927:Anticonvulsants; D002219:Carbamates; D002800:Cholinesterase Inhibitors; D006885:Hydroxybutyrates; D007202:Indicators and Reagents