1 research outputs found
Synthesis, Biological Evaluation, and Docking Studies of Tetrahydrofuran- Cyclopentanone- and Cyclopentanol-Based Ligands Acting at Adrenergic α<sub>1</sub>- and Serotonine 5-HT<sub>1A</sub> Receptors
A series of aralkylphenoxyethylamine and aralkylmethoxyphenylpiperazine
compounds was synthesized and their in vitro pharmacological profile
at both 5-HT<sub>1A</sub> receptors and α<sub>1</sub>-adrenoceptor
subtypes was measured by binding assay and functional studies. The
results showed that the replacement of the 1,3-dioxolane ring by a
tetrahydrofuran, cyclopentanone, or cyclopentanol moiety leads to
an overall reduction of in vitro affinity at the α<sub>1</sub>-adrenoceptor while both potency and efficacy were increased at the
5-HT<sub>1A</sub> receptor. A significant improvement of 5-HT<sub>1A</sub>/α<sub>1</sub> selectivity was observed in some of
the cyclopentanol derivatives synthesized (<b>4a</b> <i>cis</i>, <b>4c</b> <i>cis</i> and <i>trans</i>). Compounds <b>2a</b> and <b>4c</b> <i>cis</i> emerged as novel and interesting 5-HT<sub>1A</sub> receptor antagonist
(p<i>K</i><sub>i</sub> = 8.70) and a 5-HT<sub>1A</sub> receptor
partial agonist (p<i>K</i><sub>i</sub> = 9.25, pD<sub>2</sub> = 9.03, <i>E</i><sub>max</sub> = 47%, 5-HT<sub>1A</sub>/α<sub>1a</sub> = 69), respectively. Docking studies were performed
at support of the biological data and to elucidate the molecular basis
for 5-HT<sub>1A</sub> agonism/antagonism activity