RESUMO
Previous studies showed that 4-hydroxy-3-methoxyindolomorphinans had variable delta opioid affinity and selectivity. Herein, we show that the 3,4-dimethoxy analogs possessed similar low affinity, whereas the 3-hydroxy-4-methoxy analogs showed excellent delta opioid affinity and selectivity comparable with the parent indolomorphinans.
Assuntos
Morfinanos/farmacologia , Receptores Opioides delta/efeitos dos fármacos , Ligantes , Especificidade por SubstratoRESUMO
[reaction: see text] L-Selectride is an efficient agent for the 3-O-demethylation of opioids and is known to cleave the least hindered methoxyl group in a molecule. The treatment of a 3,4-dimethoxymorphinan containing a 6-ketal with L-Selectride gave selective 4-O-demethylation, rather than cleavage of the less hindered 3-methoxyl. In contrast, a 3,4-dimethoxymorphinan lacking a 6-ketal gave selective 3-O-demethylation, suggesting that the regiochemistry of L-Selectride-mediated O-demethylation can be manipulated through altering the position of coordination of the lithium ion.
Assuntos
Lítio/química , Morfinanos/química , Entorpecentes/química , Catálise , Indicadores e Reagentes , Estrutura Molecular , EstereoisomerismoRESUMO
To delineate the differences between the structural requirements necessary for recognition at sigma-1 and sigma-2 receptors, a range of phenethyl- and phenylpropylpiperidines were evaluated in binding assays. Phenethylpiperidines were found to favor sigma-1 receptors, whereas phenylpropylpiperidines tend to favor sigma-2 receptors. It appears that phenylpropylamine is a potential pharmacophore for selective sigma-2 ligands.