A SERIES OF N4-IMIDOETHYL DERIVATIVES OF 1-(2,3-DIHYDRO-1,4-BENZODIOXIN-5-YL)PIPERAZINE AS 5-HT1A RECEPTOR LIGANDS - SYNTHESIS AND STRUCTURE-AFFINITY RELATIONSHIPS

A series of unsubstituted and substituted succinimido, maleimido, and glutarimidoethyl derivatives of eltoprazine (3) was synthesized and te sted for affinity for the 5-HT1A receptor in rat brain homogenates. Th e unsubstituted compounds have a moderate affinity for the receptor, w hile the affinity considerably increases by substitution at or enlarge ment of these cyclic ring systems. A good correlation was found betwee n the inhibition constant K-i (expressed as pK(i)) and the lipophilici ty (clogP). No correlation was observed between the pK(i) or pK(i)(+) (local. inhibition constant) and the basicity of the N4-nitrogen atom.