Design, synthesis, and evaluation of novel, selective γ-butyrolactones sigma-2 ligands

Nearly 40 years after the first disclosure of sigma receptors, sigma-2 (σ2) receptor was recently identified as Transmembrane Protein 97 (TMEM97, also known MAC30 (Meningioma-associated protein). This macromolecule has been associated with a number disease states such schizophrenia, Alzheimer’s disease, neuropathic pain, traumatic brain injury, and cancer. We have series novel, functionalized γ-butyrolactones that are potent σ2 ligands drug-like potential candidate (9z) for future in vivo study.