Synthesis and pharmacological evaluation of novel 4-(4-fluorobenzoyl)piperidine derivatives as mixed 5-HT1A/5-HT2A/D-2 receptor ligands

A series of novel 4-(4-fluorobenzoyl)piperidine derivatives with benzothiaz olin-2-one as a pivotal template was designed, synthesised and evaluated on a battery of receptors, including serotonin 5-HT1A, 5-HT2A and 5-HT2C, dop amine D-2 and adrenergic alpha(1) receptors. The 4-(4-fluorobenzoyl)piperid ine moiety is known as one of the most potent pharmacophores for the 5-HT2A receptor. All compounds displayed high affinities for the central 5-HT2A r eceptors (1 to 10 nM) combined with high to moderate 5-HT1A (1 to 800 nM) a nd D-2 (5 to 1000 nM) affinities. Such a pharmacological profile could lead to new atypical antipsychotics. (C) Elsevier, Paris.