3-(omega-aminoalkyl)-5,5-dialkyl (or spirocycloalkyl-1',5-)hydantoins as new 5-HT1A and 5-HT2A receptor ligands

A series of new 3-(omega-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 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 (K-i = 34 and 37 nm, respectively), whereas the derivative of 1-(o-methoxyphenyl)piperazine (38) is a new, highly potent 5-HT1A receptor ligand (K-i = 0.51 nM) with a moderate affinity for 5-HT2A receptors (K-i = 213 nM).