Discovery and antiviral profile of new sulfamoylbenzamide derivatives as HBV capsid assembly modulators.

Chronic hepatitis B (CHB) is a major worldwide public health problem and novel anti-HBV therapies preventing liver disease progression to cirrhosis and hepatocellular carcinoma are urgently needed. Over the last several years, capsid assembly modulators (CAM) have emerged as clinically effective anti-HBV agents which can inhibit HBV replication in CHB patients. As part of a drug discovery program aimed at obtaining novel CAM endowed with high in vitro and in vivo antiviral activity, we identified a novel series of sulfamoylbenzamide (SBA) derivatives.

Identification of Isoform 2 Acid-Sensing Ion Channel Inhibitors as Tool Compounds for Target Validation Studies in CNS.

Acid-sensing ion channels (ASICs) are a family of ion channels permeable to cations and largely responsible for the onset of acid-evoked ion currents both in neurons and in different types of cancer cells, thus representing a potential target for drug discovery. Owing to the limited attention ASIC2 has received so far, an exploratory program was initiated to identify ASIC2 inhibitors using diminazene, a known -ASIC inhibitor, as a chemical starting point for structural elaboration. The performed exploration enabled the identification of a novel series of ASIC2 inhibitors.

Synthesis and biological evaluation of 1,3-dioxolane-based 5-HT receptor agonists for CNS disorders and neuropathic pain.

Aim: Targeting 5-HT receptor (5-HTR) as a strategy for CNS disorders and pain control.

Methodology: A series of 1,3-dioxolane-based 2-heteroaryl-phenoxyethylamines was synthesized by a convergent approach and evaluated at α-adrenoceptors and 5-HTR by binding and functional experiments. Absorption, distribution, metabolism, excretion and toxicity prediction studies were performed to explore the drug-likeness of the compounds.

Structure-Activity Relationships within a Series of σ and σ Receptor Ligands: Identification of a σ Receptor Agonist (BS148) with Selective Toxicity against Metastatic Melanoma.

A new series of spirocyclic σ receptor (σR) ligands were prepared and studied. Most were found to have a high affinity and selectivity for σ R; three compounds were shown to be σ R agonists, while another proved to be the only σ R antagonist. Only one of the σ R agonists (BS148) also exhibited σ R selectivity and was able to inhibit the growth of metastatic malignant melanoma cell lines without affecting normal human melanocytes.