Classes of Sigma2 ( σ2) Receptor Ligands: Structure Affinity Relationship (SAfiR) Studies and Antiproliferative Activity

Although several pieces of information are still missing about sigma-2 ( 2) receptor, the production of high affinity 2 receptor ligands allowed important acquisitions. Morphans such as CB64D and CB184 were the first truly 2-selective ligands synthesized, and their use in cell cultures highlighted the relationship between 2 receptors and cell proliferation, shedding light on important diagnostic and therapeutic potentials with which 2 ligands are endowed. The most significant classes of compounds are herein discussed. The design and Structure-Affinity Relationship studies (SAfiR) of 2 receptor ligands belonging to the classes of morphans, indoles (siramesine analogues), granatanes, flexible benzamides and N-cyclohexylpiperazines are reported, together with the biological results which these compounds provided giving a crucial contribution to the 2 receptor research. The pharmacophore models which were generated on the basis of different classes of the 2 ligands and the attempts for 2 receptor purification are briefly described.