Synthesis and pharmacological evaluation of acyl derivatives of phenelzine.
Acyl derivatives of phenelzine were required for pharmacological evaluation. Eight mono- and di-acyl derivatives were synthesized and characterized by gas chromatography, mass spectrometry, nuclear magnetic resonance and infrared spectrophotometry. Selective acylation was observed with both acetic anhydride and ethyl chloroformate. In aqueous medium, monoacylation yielded N1-acetyl- and N1-(ethoxy-carbonyl)-phenelzine exclusively, whereas in non-aqueous medium only N2-acetyl and N2-(ethoxycarbonyl) products were obtained. NMR temperature studies were conducted to ascertain the presence of rotational isomers and their ratios. At room temperature, one ethoxy-carbonyl and four phenelzine acetate derivatives were present as mixtures of rotamers. Preliminary evaluations of the MAO-inhibiting properties of acylated phenelzines indicate that a hydrogen atom on the N1-position of phenelzine and its derivatives is essential for activity.
Coutts
R T
RT
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Mozayani
A
A
Pasutto
F M
FM
Baker
G B
GB
Danielson
T J
TJ
D000215:Acylation; D055598:Chemical Phenomena; D002621:Chemistry; D002849:Chromatography, Gas; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis*; D010624:Phenelzine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D013055:Spectrophotometry, Infrared
D008996:Monoamine Oxidase Inhibitors; D010624:Phenelzine