A NEW POTENT RIGID ANALOGUE OF AMPHETAMINE: 2-AMINO-1,2-DIHYDRONAPHTHALENE, 2-ADN

BRUCE ALAN HATHAWAY, Purdue University

Abstract

A review of conformationally restricted ("rigid") analogues of amphetamine is presented. Based on the conformations of the analogues that are more active as stimulants, four criteria to aid in the design of rigid analogues of amphetamine are presented. Using these criteria, 2-amino-1,2-dihydronaphthalene, 2-ADN, was designed as a new rigid analogue of amphetamine. After a review of the effects of selected substitutions on the biological effects produced by amphetamine, a number of N- and phenyl-substituted analogues also were proposed for synthesis. Synthesis of 2-ADN and its phenyl-substituted analogues ultimately was carried out using a modification of the only published method. Initial efforts were made to develop new methods of synthesis, but all of these were unsuccessful. Preparation of the N,N-disubstituted derivatives was accomplished by known methods. A new method was developed for synthesis of the N-monosubstituted derivatives. Preliminary pharmacological evaluation revealed that 2-ADN is about one-fourth as potent as (+)-amphetamine as a stimulant in mice. The S-(-) isomer is responsible for the stimulant effects. It was found that 2-ADN also is about one-fourth as potent as (+)-amphetamine in producing stereotyped behavior in rats. Both reserpine and alpha methyl para tyrosine antagonize the stimulation produced by 2-ADN.

Degree

Ph.D.

Subject Area

Organic chemistry

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