N-(1-Arylpropionyl)-4-aryltetrahydropyridines, a new class of high-affinity selective .sigma. receptor ligands
| Autor: | William Frietze, Guyanand Singh, Randall B. Murphy, George Stoupakis, David I. Schuster, George Lem, George K. Ehrlich, Yan Ping Pan, Bing Cai |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Dihydropyridines
Pyridines Stereochemistry Sigma receptor Binding Competitive Radioligand Assay Cerebellum Dopamine receptor D2 Drug Discovery Animals Receptors sigma Potency Binding site Receptor IC50 Propiophenones Binding Sites Receptors Dopamine D2 Chemistry Biological activity Spiperone Receptors Serotonin Haloperidol Molecular Medicine Cattle Ketanserin Pharmacophore Antipsychotic Agents |
| Zdroj: | Journal of Medicinal Chemistry. 36:3923-3928 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | A series of N-(1-arylpropionyl)-4-aryl-1,2,3,6-tetrahydropyridines, prepared by simple Mannich condensations, have been found by radioligand binding assays to have moderate to high affinity (IC50 0.5-500 nM) for bovine cerebellar sigma receptor/binding sites and no measurable affinity (IC50 > 5000 nM) for bovine striatal D2 receptors. The most active of these compounds rival in potency the most active sigma ligands previously reported. Three of these sigma-active compounds were screened for pharmacological activity under the NIMH-NovaScreen program and showed moderate affinity only for D2 and 5-HT2 receptors among the 40 sites assayed. Since these N-(1-arylpropionyl)-4-aryltetrahydropyridines are structurally related to other potent sigma receptor ligands, in particular haloperidol and 4-phenylpiperidines, these data provide insights into the nature of the essential pharmacophore of the sigma receptor. The selective affinity of these materials for sigma receptors indicates they have potential as prototypes of novel psychotherapeutic medicinal agents, particularly as antipsychotic drugs which would be devoid of debilitating side effects associated with blockade of D2 receptors. |
| Databáze: | OpenAIRE |
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