Design, synthesis and evaluation of the first highly selective sigma-2 receptor ligand

MEDI 335

Sanju Narayanan, slnu@olemiss.edu1, Christophe Mesangeau, christophemesangeau@yahoo.fr1, Jamal Shaikh2, Rae R. Matsumoto3, Jacques H. Poupaert4, and Christopher R. McCurdy, cmccurdy@olemiss.edu5. (1) Department of Medicinal Chemistry and Laboratory for Applied Drug Design and Synthesis, University of Mississippi, 417 Faser Hall, University, MS 38677, (2) Department of Pharmacology, School of Pharmacy, University, MS 38677, (3) Department of Pharmacology, School of Pharmacy, Research Institute of Pharmaceutical Sciences, University, MS 38677, (4) Universite Catholique de Louvain, Avenue Emmanuel Mounier 73,B-1200,Brussels, Belgium, Avenue Emmanuel Mounier 73, B-1200, Brussels, Belgium, (5) Department of Medicinal Chemistry and Laboratory for Applied Drug Design and Synthesis, RIPS, University of Mississippi, 417 Faser Hall, University, MS 38677
Sigma receptors (s-1 and s-2) are a well-defined receptor class, distinct from opioid and phencyclidine binding sites. They are present in the central nervous system as well as in various peripheral tissues. The s-1 receptor has been demonstrated to be involved in acute and chronic effects of cocaine and methamphetamine toxicities, while activation of the s-2 receptor induces growth arrest and cell death in various tumour cell lines. The mechanism by which s-2 ligands induce cytotoxicity, however, remains unknown. This is partially due to the fact that several s-2 signaling studies have been done by existing nonselective s ligands that bind both s-1 and s-2 receptor. In this regard, searching for selective high affinity s-1 and s-2 ligands led to the design and synthesis of the first highly selective s-2 ligand derived from a series of compounds developed in our lab.
 

Poster Session
7:00 PM-9:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007