Synthesis, docking studies and biological evaluation of benzo[b]thiophen-2-yl-3-(4-arylpiperazin-1-yl)-propan-1-one derivatives on 5-HT1A serotonin receptors.
A series of novel benzo[b]thiophen-2-yl-3-(4-arylpiperazin-1-yl)-propan-1-one derivatives 6a-f, 7a-f and their corresponding alcohols 8a-f were synthesized and evaluated for their affinity towards 5-HT(1A) receptors. The influence of arylpiperazine moiety and benzo[b]thiophene ring substitutions on binding affinity was studied. The most promising analogue, 1-(benzo[b]thiophen-2-yl)-3-(4-(pyridin-2-yl)piperazin-1-yl)propan-1-one (7e) displayed micromolar affinity (K(i) = 2.30 μM) toward 5-HT(1A) sites. Docking studies shed light on the relevant electrostatic interactions which could explain the observed affinity for this compound.
Departamento de Química Orgánica y Fisicoquímica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Casilla 233, Santiago 1, Chile. hpessoa@ciq.uchile.cl
Hernán
H
Pessoa-Mahana
Gonzalo
G
Recabarren-Gajardo
Jenny Fiedler
JF
Temer
Gerald
G
Zapata-Torres
C David
CD
Pessoa-Mahana
Claudio Saitz
CS
Barría
Ramiro
R
Araya-Maturana
D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects*; D021241:Spectrometry, Mass, Electrospray Ionization
D010879:Piperazines; D044282:Receptor, Serotonin, 5-HT1A