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

✍ Scribed by Hanna Byrtus; Maciej Pawlowski; Sijka Charakchieva-Minol; Beata Duszyńska; Maria J. Mokrosz; Jerzy L. Mokrosz; Alfred Zejc

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 676 KB
• Volume: 329
• Category: Article
• ISSN: 0365-6233
• DOI: 10.1002/ardp.19963290604

✦ Synopsis

A series of new 3-(o-aminoalkyl)-S,S-disubstituted hydantoins, containing 1 -pheny lpiperazine, 1 -(o-methoxy pheny 1)piperazine or 1,2,3,4-tetrahydroisoquinoline fragments, were synthesized by standard alkylation procedures and their 5-HTIA and 5 -m ~~ receptor affinities were determined. It has been shown that the investigated derivatives are recognized by S-HTIA and S -H T ~A receptors due to the presence of a I-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 I-phenylpiperazine derivatives 32 and 36 are new, selective 5-HT2.a, receptor ligands (Xi = 34 and 37 nM, respectively), whereas the derivative of 1-(o-methoxypheny1)piperazine (38) is a new, highly potent ~-H T I A receptor ligand (Ki = 0.5 I nM) with a moderate affinity for S -H T ~A receptors (K = 213 nM).