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Conversion of a highly selective sigma-1 receptor-ligand to sigma-2 receptor preferring ligands with anticocaine
Christophe Mésangeau1, Sanju Narayanan, Andrea M Green
1Department of Medicinal Chemistry, The University of Mississippi, Mississippi 38677, USA.
Abstract:
Cocaine's toxicity can be mitigated by blocking its interaction with sigma-1 receptors. The involvement of sigma-2 receptors remains unclear. To investigate their potential role, we have designed compounds through a convergent synthesis utilizing a highly selective sigma-1 ligand and elements of a selective sigma-2 ligand. Among the synthesized compounds was produced a subnanomolar sigma-2 ligand with an 11-fold preference over sigma-1 receptors. These compounds may be useful in developing effective pharmacotherapies for cocaine toxicity.
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