Synthesis, pharmacophore modeling, and biological evaluation of novel 5h-thiazolo[3,2-A]pvrimidin-5-one derivatives as 5-HT 2A receptor antagonists

Abstract

Novel 5H-thiazolo[3,2-a]pyrimidin-5-one derivatives linked through an ethylene bridge to various phenylpiperazine groups were prepared for evaluation as 5-HT 2A receptor antagonists. The target compounds 11a-p were prepared through the initial synthesis of the 2-chloroethyl intermediates 10a-d which were then reacted with the appropriate phenylpiperazines. All compounds were tested for their antagonistic activity on 5-HT 2a receptors using inhibition of 5-hydroxytryptophan(5-HTP)-induced head twitches in mice. Pharmacophore modeling study, based on a hypothetical pharmacophore template generated from a set of diverse known active ligands, revealed good fitting of the designed compounds to the generated hypothetical pharmacophore. © Osterrechische Apotheker-Verlagsgedellschaft m.b.H.