N-(1-arylpropionyl)-4-aryltetrahydropyridines, a new class of high-affinity selective sigma receptor ligands.

ID: ALA1126928

Journal: J Med Chem

Title: N-(1-arylpropionyl)-4-aryltetrahydropyridines, a new class of high-affinity selective sigma receptor ligands.

Authors: Schuster DI, Pan YP, Singh G, Stoupakis G, Cai B, Lem G, Ehrlich GK, Frietze W, Murphy RB.

Abstract: 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.

CiteXplore: 7902869

DOI: 10.1021/jm00076a021

Patent ID: ┄