Document Report Card

ID: ALA1127639

Journal: J Med Chem

Title: Structural features important for sigma 1 receptor binding.

Authors: Glennon RA, Ablordeppey SY, Ismaiel AM, el-Ashmawy MB, Fischer JB, Howie KB.

Abstract: Two problems that have hampered sigma receptor research are (i) a lack of high-affinity agents and (ii) the recent identification of multiple populations of sigma receptors (i.e., sigma 1 and sigma 2 sites). Recently, several high-affinity sigma ligands have been identified, and the term superpotent sigma ligands has been coined to describe agents with Ki values of < 1 nM. We have previously shown that appropriately N-substituted phenylalkylamines bind at sigma receptors with high affinity. In the present investigation, we examine the structure-affinity relationships of these phenylalkylamine derivatives for sigma 1 binding and describe some of the first superpotent sigma 1 ligands. A binding model was developed to account for the structural features of the phenylalkylamines that appear to be important for the interaction of these agents with sigma 1 sites.

CiteXplore: 8164264

DOI: 10.1021/jm00034a020