title: 3-(omega-Aminoalkyl)-5,5-dialkyl(or spirocycloalkyl-1',5-)hydantoins as new 5-HT1A and 5-HT2A receptor ligands.
abstract: 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 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).
authors.affiliation: Department of Pharmaceutical Chemistry, Collegium Medicum, Jagiellonian University, Kraków, Poland.
authors.forename: H
authors.initials: H
authors.lastname: Byrtus
authors.forename: M
authors.initials: M
authors.lastname: Pawłowski
authors.forename: S
authors.initials: S
authors.lastname: Charakchieva-Minol
authors.forename: B
authors.initials: B
authors.lastname: Duszyńska
authors.forename: M J
authors.initials: MJ
authors.lastname: Mokrosz
authors.forename: J L
authors.initials: JL
authors.lastname: Mokrosz
authors.forename: A
authors.initials: A
authors.lastname: Zejc
mesh_terms: D000588:Amines / Q000737:chemistry / Q000378:metabolism; D000928:Antidepressive Agents / Q000138:chemical synthesis / Q000494:pharmacology; D006827:Hydantoins / Q000138:chemical synthesis* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis / Q000494:pharmacology; D011485:Protein Binding; D011985:Receptors, Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014196:Trazodone / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000588:Amines; D000928:Antidepressive Agents; D006827:Hydantoins; D010880:Piperidines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C013528:etoperidone; D014196:Trazodone