Central Stimulants. Chemistry and Structure-Activity Relationships of Aralkyl Hydrazines

Abstract

The replacement of an amino or alkylamino group by a hydrazino or alkyl hydrazino moiety in a variety of aralkylamines has yielded a group of potent central stimulants which produce their effect by a dual mechanism: (1) direct stimulation of the central nervous system (analeptic action), and (2) powerful inhibition of the enzyme monoamine oxidase (MAO) which is responsible for the metabolic destruction of endogenous central excitatory hormones. Definite structure-activity relationships have been established and will be discussed. One of the compounds, N-aminoamphetamine, displayed forty times the MAO inhibitory potency of iproniazid (Marsilid). The synthesis of the aralkyl hydrazines was accomplished via the reductive hydrazinolysis of phenyl-alkanones or reaction of hydrazine with a phenylalkyl halide. The nature of the products obtained was dependent on the reaction conditions. It is demonstrated also that the Raney nickel cleavage of substituted hydrazines constitutes a convenient means of obtaining pure primary and secondary amines. © 1959, American Chemical Society. All rights reserved.