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 (sigma(2)) receptor, the production of high affinity sigma(2) receptor ligands allowed important acquisitions. Morphans such as CB64D and CB184 were the first truly sigma(2)-selective ligands synthesized, and their use in cell cultures highlighted the relationship between sigma(2) receptors and cell proliferation, shedding light on important diagnostic and therapeutic potentials with which sigma(2) ligands are endowed. The most significant classes of compounds are herein discussed. The design and Structure-Affinity Relationship studies (SAfiR) of sigma(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 sigma(2) receptor research. The pharmacophore models which were generated on the basis of different classes of the sigma(2) ligands and the attempts for sigma(2) receptor purification are briefly described.