Synthesis and dopamine receptor binding of 4-(2-aminoethyl)-1H-pyrazole and its N,N-dialkyl derivatives

The agnostic activity of Quinpirole (3a) a; the D 2 dopamine (DA) receptor suggested that the dopaminergic pharmacophore embedded in 3a was the 4-(2-aminoethyl)-1H-pyrazole (5) moiety. On that basis we have synthesized some derivatives of 5 bearing on the amino group alkyl and alkylaryl substituents. The affinities of 5 and its derivatives for the D 1 and D 2 DA receptor subtypes were evaluated in rat striatum by binding assays. None of these compounds show affinity for the D 1 receptor. In the D 2 binding assay only the N,N-di-(2-phenylethyl) (5i) and N-n-propyl-N-[2-(3-hydroxyphenyl)ethyl] (5j) derivatives show affinities comparable to that of Quinpirole. These results do not support the postulate that the 4-(2-aminoethyl)1H-pyrazole is a bioisostere of the catechol nucleus of DA