No âmbito de uma linha de pesquisas que trata do planejamento, síntese e avaliação farmacológica de novos candidatos a protótipos de agentes neuroativos, descrevemos neste trabalho a síntese e avaliação farmacológica de novo análogo do nebracetam contendo a unidade 2-aza-biciclo[3.3.0]octano, planejado como candidato a agente nootrópico útil para o tratamento da doença de Alzheimer. A avaliação das propriedades ao nível dos neurônios do sistema nervoso central utilizando a técnica do "path-clamp" não permitiu evidenciar um perfil de ação central adequado para o novo composto.

As part of a research program aiming at the design, synthesis and pharmacological evaluation of a novel lead-candidates of neuroactive compounds, we describe herein the synthesis and the central profile of a new nebracetam analog having a 2-aza-bicyclo[3.3.0]octane system. The new derivative, designed on the basis of the conformational restriction concept, was synthesized in good yields exploring a diastereoselective reductive-amination and cyclization one-pot sequence. The pharmacological profile of this new compound, investigated by using path-clamp techniques on neurons of the CNS, indicated no effects on these cells.

In this communication we describe a new methodology to Dieckmann cyclization of diethyl adipate (1) and diethyl pimelate (3) applying "push-pull" strategy using anhydrous aluminium trichloride and triethylamine in dichloromethane at room temperature. This method is very efficient, simple, safe and reproducible, giving the corresponding cyclic β-keto ester derivatives in 84% and 71% yield, respectively.