1 A number of aromatic-N-propargyl (acetylenic) compounds and indoleamines were tested for their inhibitory action on monoamine oxidase (MAO) type A and type B using the substrates 5-hydroxytryptamine (5-HT), f3-phenylethylamine (PEA) and dopamine.2 Structure activity studies with aromatic-N-propragyl (acetylenic) derivatives have shown that MAO inhibitory potency is least dependent on the aromatic portion of the compounds. N-methylated propargyl derivatives are the most active and replacement of the methyl group with a higher alkyl or aromatic group results in significant reduction of activity. The triple bond in the N-propargyl portion-is absolutely essential for activity and must be 8-to the nitrogen. It is the acetylenic group that gives these compounds their irreversible MAO inhibitory property. 3 The present study has indicated that since the acetylenic compounds resemble the enzyme substrates the distance between the aromatic ring and the N-propargyl terminal is crucial in designating the type A or type B MAO inhibitory property. For MAO type A inhibition, a distance equivalent to at least three carbon units is required, while for the inhibition of the B type enzyme this distance can be 1 or 2 carbon units. 4 The compounds AGN-1133 and AGN-1135 show most promise in Parkinson's disease or as anti-depressants because of their irreversible selective type B MAO inhibition in vitro and in vivo. 5 A number of indoleamine derivatives were found to be reversible selective type A inhibitors.
A series of S,K-substituted 1-arylcycloheuylamines was prepared mainly by the reaction of an arylmagnesiuni hromide and 1-dialkylaminocyclohexanecarbonitrile. As the cyclopentyl analog could not be obtained by this way, condensation of 1-phenylcyclopentylamine with pentamethylene dibromide in D I I F was tried with success. These compounds were tested for their psychopharmacological properties. 1-[l-( 2-Thienyl)cyclohesyl]piperidine (16) was found to be the most active.The pharmacological properties of 1-( l-phenylcyclohexj 1)piperidine (7)3 (phenyl~yclidine~-~), for which a t the time of this investigatioii only one synthesis has beeii stimulated the exploration of possible preparative routes applicable also to other members of the series.
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