Piperidinyltetralin sigma ligands.

Sigma receptor ligands have been proposed to be potential antipsychotic drugs based on their activity profile in animal behavioral models and their indirect modulation of dopaminergic function. Compound 15 (DuP 734) is a combined antagonist of sigma-1 and serotonin 5HT2 receptors, which has been entered into phase I clinical trials as a potential antipsychotic drug. Tetralins 1 and 2 were prepared to determine whether restriction of the conformation of 15 and its analogs may lead to differences in binding selectivity or in vivo profile.

3-Substituted, 3-(4-pyridinylmethyl)-1,3-dihydro-1-phenyl-2H-indol-2-ones as acetylcholine release enhancers: synthesis and SAR.

A series of 3-substituted, 3-(4-pyridinylmethyl)-1,3-dihydro-1-phenyl-2H-indol-2-ones was synthesized and found to enhance the stimulus-induced release of neurotransmitter acetylcholine (AcCh), and by doing so, might be useful in treating cognitive disorders where the level of this neurotransmitter may be diminished in the brain, as in Alzheimer's disease. An attempt has been made to correlate the structure of the 3-substitution with the ability of the compounds to enhance the release of AcCh from the striatum region of rat brain preparations.

Novel piperidine sigma receptor ligands as potential antipsychotic drugs.

sigma receptor ligands represent a new class of potential antipsychotic drugs. This paper presents the structure-activity relationships leading to novel disubstituted piperidine sigma ligands, which have little or no affinity for dopamine D2 receptors. Selectivity for sigma sites over dopamine D2 or serotonin 5-HT2 receptors appears to be governed by the chemical nature of the piperidine nitrogen substituent, its distance from the basic nitrogen, and its orientation relative to the other piperidine substituent.