| 20060623 |
Czopek A, Byrtus H, Kolaczkowski M, Pawlowski M, Dybala M, Nowak G, Tatarczynska E, Wesolowska A, Chojnacka-Wojcik E: Synthesis and pharmacological evaluation of new 5-(cyclo) alkyl-5-phenyl- and 5-spiroimidazolidine-2,4-dione derivatives. Eur J Med Chem. 2010 Apr;45(4):1295-303. Epub 2009 Dec 6.
Novel 5-HT1A receptor agonist with potential antidepressant and anxiolytic activity.. The synthesis of 5-(cyclo) alkyl-5-phenyl- and 5-spiroimidazolidine-2,4-dione derivatives with an arylpiperazinylpropyl moiety (12-23) and their in vitro and in vivo pharmacological properties and molecular characteristics were described. The investigated compounds exhibited high affinity for 5-HT (1A) (13-22) and 5-HT (2A) (18, 20, 21, 23) receptors and diversified pharmacological profile. Compounds 17, 20 and 22 showed antagonistic, partial agonistic and agonistic activity, respectively, toward 5-HT (1A) receptor and they were investigated as potential antidepressants and/or anxiolytics. The most interesting compound 22 (1-[3-(4-(2-methoxyphenyl) piperazin-1-yl) propyl]-3',4'-dihydro-2'H-spiro [i midazolidine-4,1'-naphthalene]-2,5-dione), a pre- and postsynaptic 5-HT (1A) receptor agonist produced an antidepressant-like effect, which was more pronounced than that of imipramine in the forced swim test in mice, without affecting locomotor activity. Moreover, compound 22 produced a weak anxiolytic-like effect in the four-plate test in mice. Molecular docking studies of compound 22 to the homology model of the 5-HT (1A) receptor showed that a 3',4'-dihydro-2'H-spiro [imidazolidine-4,1'-naphthalene]-2,5-dione moiety played an important role in stabilizing the ligand-receptor complex. |
65(0,2,2,5) |