Development of selective agents targeting serotonin 5HT1A receptors with subnanomolar activities based on a coumarin core. Issue 8 (25th July 2017) - Ostrowska, K.
Abstract : A screening of 18 compounds identified five coumarin derivatives with subnanomolar activity against the 5HT1A receptor. Abstract : A series of 18 new 5-[3-(4-aryl-1-piperazinyl)propoxy]coumarin derivatives from the corresponding bromoalkyl derivatives have been designed and synthesized by us using a microwave-assisted protocol. Radioligand binding assays of this series of compounds as well as a previously synthesized series of 17 structurally-similar compounds showed that six systems have very high affinities to the 5-HT1A receptor (0.3–1.0 nM) and good selectivity against the 5-HT2A receptor. Molecular docking, structural studies and structure–activity relationship studies were used to gain more insight into the atomistic details of ligand binding and rationalize the obtained results.