Homologous piperazine-alcanols: chiral pool synthesis and pharmacological evaluation

MedChemComm
2012.0

Abstract

Starting with the proteinogenic amino acids (S)-aspartate and (S)-glutamate the homologous piperazine-alcanols 3 and 4 were prepared in a five step synthesis. The diversity was introduced by N-1 alkylation of the piperazinediones 5 and 6 with various alkyl halides. Subsequent LiAlH4 reduction of the dioxopiperazine-esters 7 and 8 provided the alcohols 3 and 4. The ethanol derivatives 3 show similar σ1 affinity as the methanol derivatives 2, but increased selectivity over the σ2 subtype. The corresponding propanol derivatives 4 are considerably less potent. A benzyl or dimethylallyl residue at N-1 appears to be optimal for high σ1 affinity.

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