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ID: ALA2029272

Journal: Bioorg Med Chem Lett

Title: 7-Azabicyclo[2.2.1]heptane as a scaffold for the development of selective sigma-2 (σ2) receptor ligands.

Authors: Banister SD, Rendina LM, Kassiou M.

Abstract: A series of N-substituted 7-azabicyclo[2.2.1]heptanes (12-17 and 22-25) and similarly substituted pyrrolidines (32-36 and 41-44) were synthesized as sterically-reduced, achiral analogs of adamantane- and trishomocubane-derived σ ligands. In vitro competition binding assays against σ receptors revealed that arylalkyl N-substituents conferred selectivity for the σ(2) subtype, while alicyclic or polycarbocyclic substituents imparted high affinity for both subtypes. The σ(2) binding and subtype selectivities of N-arylalkyl-7-azanorbornanes was generally greater than the analogously-substituted pyrrolidines, indicating that steric bulk and conformational restriction around the nitrogen atom are likely important for subtype discrimination.

CiteXplore: 22607684

DOI: 10.1016/j.bmcl.2012.04.077