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Cite thit: DOI: 10.1039/c7md00281e

Development of selective agents targeting serotonin SHTiA receptors with subnanomolar activities based on a coumarin coret

K. Ostrowska. ©** D. Grzeszczuk,' M. Głuch-Lutwin,^b A. Gryboś.^b A. Siwek.^b Ł. Dobrzycki^c and B. Trzaskowski©⁰

Received 31st May 2017, Accepted 23rd June 2017

DOI: 10.1039/c7md00281e

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A series of 18 new 5-|3-(4-aryl-l-piperazinyl}propoxy]coumarin derivatrves from the corresponding bromo-alkyt derrvatives have been designed and synthesized by us using a microwave-assisted protocol Radioligand binding assays of this series of compounds as wetl as a previously synthesized series of 17 structuraUy-similar compounds showed that six Systems have very high affinities to the 5-HT_w receptor (0.3-1.0 nM) and good selectkrity against the 5-HT₂a receptor. Molecular docking. structural studies and structure-activity relationship studies were used to gam morę msight into the atomistic details of ligand binding and rationatize the obtained resUts.