1027138-18-6Relevant articles and documents
Synthesis and structure-activity relationships of N-(1-benzylpiperidin-4-yl)arylacetamide analogues as potent σ1receptor ligands
Huang,Hammond,Wu,Mach
, p. 4404 - 4415 (2007/10/03)
A series of N-(1-benzylpiperidin-4-yl)arylacetamides were synthesized and evaluated for their binding properties for σ1 and σ2 receptors. In agreement with previously reported σ1/σ2 receptor binding data for N-(1-benzylpiperidin-4-yl)phenylacetamide, all of the N-(1-benzylpiperidin-4-yl)arylacetamide compounds reported below displayed higher affinity for σ1 vs σ1 receptors. Replacement of the phenyl ring of the phenylacetamide moiety with a thiophene, naphthyl, or indole aromatic ring had no significant effect on the σ1 receptor affinity. Replacement of the phenyl ring with an imidazole or pyridyl aromatic ring resulted in a >60-fold loss in affinity for σ1 receptors and no significant binding affinity for σ2 receptors. Substitution on the aromatic ring of the benzyl group showed a similar or slightly decreased affinity for σ1 receptors. Substitution on the aromatic rings of both the phenylacetamide moiety and the benzyl group with a halogen resulted in a similar affinity for σ1 receptors and a significantly increased affinity for σ2 receptors. Comparative molecular field analysis revealed that electrostatic properties of the substituents in the phenylacetamide aromatic ring strongly influenced binding to σ1 receptors. Compounds 1, 10, 18, 22, 37, and 40 showed the highest selectivity for σ1 receptors with Ki (σ2) to Ki (σ1) ratios of 100, >92, >122, 77, 74, and 80, respectively. In agreement with previously reported results, the phenylacetamide analogues had no binding affinity for dopamine receptors (D2/D3).
