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 tested for affinity for the 5-HT1A receptor in rat brain homogenates. The unsubstituted compounds have a moderate affinity for the receptor, while the affinity considerably increases by substitution at or enlargement of these cyclic ring systems. A good correlation was found between the inhibition constant Ki (expressed as pKi) and the lipophilicity (clogP). No correlation was observed between the pKi or pKi+ (local inhibition constant) and the basicity of the N4-nitrogen atom.