3-(ω-Aminoalkyl)-5,5-dialkyl(or spirocycloalkyl-1′,5-)hydantoins as New 5-HT1A and 5-HT2A Receptor Ligands

A series of new 3‐(ω‐aminoalkyl)‐5,5‐disubstituted hydantoins, containing 1‐phenylpiperazine, 1‐(o‐methoxyphenyl)piperazine or 1,2,3,4‐tetrahydroisoquinoline fragments, were synthesized by standard alkylation procedures and their 5‐HT1A and 5‐HT2A receptor affinities were determined. It has been shown that the investigated derivatives are recognized by 5‐HT1A and 5‐HT2A receptors due to the presence of a 1‐arylpiperazine fragment; however, the terminal hydantoin moiety plays an important role in stabilization of the receptor‐ligand complex. It has also been found that the two 1‐phenylpiperazine derivatives 32 and 36 are new, selective 5‐HT2A receptor ligands (Ki = 34 and 37 nM, respectively), whereas the derivative of 1‐(o‐methoxyphenyl)piperazine (38) is a new, highly potent 5‐HT1A receptor ligand (Ki = 0.51 nM) with a moderate affinity for 5‐HT2A receptors (Ki = 213 nM).