Synthesis and binding properties of novel selective 5-HT3 receptor ligands

Abstract This work reports on the synthesis and affinities for the 5-HT 3 versus the 5-HT 4 receptor of new piperazinyl-substituted thienopyrimidine derivatives 20 – 45 with a view to identify potent and selective ligands for the 5-HT 3 receptor. Some of the new compounds show good affinity for the 5-HT 3 receptor and, notably, do not display any affinity for the 5-HT 4 receptor. 4-(4-Methyl-1-piperazinyl)-2-methylthio-6,7-dihydro-5 H -cyclopenta[4,5]thieno[2,3- d ]pyrimidine 31 exhibits the highest affinity for the 5-HT 3 receptor ( K i =33 nM) and behaves as noncompetitive antagonist.