The sigma-2 receptor is highly expressed in various rapidly proliferating cancer cells and regarded as a cancer cell biomarker. Selective sigma-2 ligands have been shown to specifically label the tumor sites, induce cancer cells to undergo apoptosis, and inhibit tumor growth. Sigma-2 ligands are potentially useful as cancer diagnostics, anticancer therapeutics, or adjuvant anticancer treatment agents. However, both the cloning of this receptor and the identification of its endogenous ligand have not been successful, and the lack of structural information has severely hindered the understanding of its physiological roles, its signaling pathways, and the development of more selective sigma-2 ligands. Recent data have implicated that sigma-2 binding sites are within the lipid rafts and that PGRMC1 (progesterone receptor membrane component 1) complex and sigma-2 receptor may be coupled with EGFR (epidermal growth factor receptor), mTOR (mammalian target of rapamycin), caspases, and ion channels. Due to its promising applications in cancer management, there are rapidly increasing research efforts that are being directed into this field. This review article updates the current understanding of sigma-2 receptor and its potential physiological roles, applications, interaction with other effectors, with special focuses on the development of sigma-2 ligands, their chemical structures, pharmacological profiles, applications in imaging and anticancer therapy.

An improved process for the preparation of 1-indanones from various benzoic acids is described. This process involves a Friedel–Crafts acylation between a substituted benzoyl chloride and ethylene, followed by an intramolecular Friedel–Crafts alkylation in the presence of aluminum chloride. The described process combines three steps into a one-pot process, is scalable, is cost-effective, and thus has a general applicability in manufacturing production of various 1-indanones.

Aryl halide (Br, Cl, I) is among the most important compounds in pharmaceutical industry, material science, and agrochemistry, broadly utilized in diverse transformations. Tremendous approaches have been established to prepare this scaffold; however, many of them suffer from atom economy, harsh condition, inability to be scaled up, or cost-unfriendly reagents and catalysts. Inspired by vanadium haloperoxidases herein we presented a biomimetic approach for halogenation (Br, Cl, I) of (hetero)arene catalyzed by tungstate under mild pH in a costefficient and environment-and operation-friendly manner. Broad substrates, diverse functional group tolerance, and good chemo-and regioselectivities were observed, even in late-stage halogenation of complex molecules. Moreover, this approach can be scaled up to over 100 g without time-consuming and costly column purification. Several drugs and key precursors for drugs bearing aryl halides (Br, Cl, I) have been conveniently prepared based on our approach.

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C2, C3-disubstituted indole is one of the most frequently encountered motifs in bioactive alkaloids and medicinal chemistry. Thus, developing novel, concise, and efficient access to it is highly desired in drug discovery. Herein, we present such an approach to this scaffold by direct oxidative coupling of C2-substituted indoles and enolates. Compared with indole bearing no C2-substituent, higher yields (up to 96%) were obtained for C2-substituted indoles in most cases. Mechanistic studies showed the reaction went through a Fe-chelated radical-anion oxidative coupling procedure promoted by C2-substituent on indole by two means: (1) stabilizing C2-radical intermediate during the reaction; (2) reducing indole homocoupling. This approach serves as a synthetic useful tool to quickly build up bioactive small molecule library of C2, C3-disubstituted indoles, and several products showed promising anticancer activities. Besides, indomethacin and its analogs were conveniently prepared in three-step sequence efficiently, indicating the potential application of our approach in medicinal chemistry.

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