Synthesis of some [N-(2-haloalkyl)amino]tetralin derivatives as potential irreversible labels for bovine anterior pituitary D2 dopamine receptors

A series of hydroxylated 2-aminotetralins were prepared in the search for irreversible labels for D2 dopamine receptors. N-2-Haloacetyl and N-2-haloalkyl substituents were chosen as potential receptor alkylating groups. Titrimetric studies were carried out on [N-(chloroethyl)-N-methylamino]tetralins 10, 10a, 24, and 26 to demonstrate that aziridinium ions were formed as reactive intermediates from these compounds. This observation was confirmed by 1H NMR studies on compound 10. The majority of the aminotetralins prepared showed reasonably high affinity binding to anterior pituitary D2 dopamine receptors and exhibited agonist properties. Structure-activity results are presented together with preliminary studies designed to identify irreversible receptor binding agents. [N-(2-Chloroethyl)-N-propylamino]-6,7-dihydroxytetralin hydrobromide (18) proved most promising in these studies.