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Piperidinyltetralin sigma ligands.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 1994 Feb 04; Vol. 37 (3), pp. 364-70. - Publication Year :
- 1994
-
Abstract
- 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. The syntheses and the structure-activity relationships of these compounds are reported herein. A reduced derivative, 14, had high affinity for sigma-1 and serotonin 5HT2 receptors as well as excellent oral activity in some animal antipsychotic models. Furthermore, compound 14 failed to cause catalepsy in the rat up to 90 mg/kg (po).
- Subjects :
- Aggression drug effects
Animals
Antipsychotic Agents metabolism
Antipsychotic Agents pharmacology
Behavior, Animal drug effects
Ligands
Mescaline antagonists & inhibitors
Mescaline pharmacology
Mice
Molecular Structure
Piperidines metabolism
Piperidines pharmacology
Receptors, Serotonin metabolism
Structure-Activity Relationship
Tetrahydronaphthalenes pharmacology
Antipsychotic Agents chemical synthesis
Piperidines chemical synthesis
Receptors, sigma metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-2623
- Volume :
- 37
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 7905926
- Full Text :
- https://doi.org/10.1021/jm00029a008