Synthesis and affinities for dopamine (D2) and 5-hydroxytryptamine (5-HT2A) receptors of 1-(benzoylpropyl)-4-(1-oxocycloalkyl-2-ethyl)-piperazines as cyclic butyrophenone derivatives.

Abstract

Starting from benzo- or thienocycloalkaneacetic acids, we have prepared a series of 1-(3-p-fluorobenzoylpropyl)-4-(1-oxo-benzo- or thienocycloalkyl-2-ethyl)piperazines 8a-e containing both semirigid and linear butyrophenones pharmacophores. The affinities of these compounds for dopamine (D2) and 5-hydroxytryptamine (5-HT2A) receptors were evaluated in vitro in receptor-binding assays and in functional experiments. The ratios of pKi's for 5-HT2A/D2 receptors may be useful for rapid screening of new compounds and assessing potential induction of extrapyramidal symptoms; ratio values > or = 1.12 (Meltzer's ratio) are predictive of an atypical antipsychotic profile. The new molecules had a ratio in the range of 0.96-1.11 while haloperidol showed a ratio of 0.93. The 2-piperazinoethyl thiotetralone derivative 8d (QF 0506B) with a ratio of 1.11 was the most active compound.

Cite this paper

@article{Ravia1996SynthesisAA, title={Synthesis and affinities for dopamine (D2) and 5-hydroxytryptamine (5-HT2A) receptors of 1-(benzoylpropyl)-4-(1-oxocycloalkyl-2-ethyl)-piperazines as cyclic butyrophenone derivatives.}, author={Enrique Ravi{\~n}a and Juan Fueyo and Christian F Masaguer and Juan Andr{\'e}s Negreira and Javier del Cid and Iraida Luz Orozco Loza and Alberto Honrubia and Helena Trist{\'a}n and T G-Ferreiro and Jos{\'e} Angel Fontenla and Elyse Rosa and Jose Mar{\'i}a L{\'o}pez-Arcas Calleja and Maria L de Ceballos}, journal={Chemical & pharmaceutical bulletin}, year={1996}, volume={44 3}, pages={534-41} }