Activity of N-(2-phenylethyl)-N-n-propyl-2-(3-hydroxyphenyl) ethylamine derivatives as dopamine receptor ligands.

The N-n-propyl-N-(2-phenylethyl)-2-(3-hydroxyphenyl)ethylamine (1, RU 24213) had been previously identified as selective agonist of DA D2 receptor subtype. In this paper we describe the synthesis and in vitro binding affinities of several derivatives of 1 substituted with fluorine, chlorine and methyl or hydroxy groups on the phenyl ring of the N-2-phenylethyl moiety. The results obtained indicate that these substitutions do not improve the D2 binding affinity. The introduction on the phenyl ring of two fluorine or chlorine atoms decreases with D1 affinity, and the dichloro derivatives are highly selective for the D2 receptor. Preliminary behavioural tests confirm that the dichloro derivatives behave as D2 selective agonists.