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 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).
Byrtus
H
H
Department of Pharmaceutical Chemistry, Collegium Medicum, Jagiellonian University, Kraków, Poland.
Pawłowski
M
M
Charakchieva-Minol
S
S
Duszyńska
B
B
Mokrosz
M J
MJ
Mokrosz
J L
JL
Zejc
A
A
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
D000588:Amines; D000928:Antidepressive Agents; D006827:Hydantoins; D010880:Piperidines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C013528:etoperidone; D014196:Trazodone