Reductive Cleavage of Organic Peroxides by Iron Salts and Thiols.

Despite the low bond strength of the oxygen-oxygen bond, organic peroxides are often surprisingly resistant to cleavage by nucleophiles and reductants. As a result, achieving decomposition under mild conditions can be challenging. Herein, we explore the reactivity of a selection of peroxides toward thiolates, phenyl selenide, Fe(II) salts, and iron thiolates.

Identification and Characterization of Influenza Virus Entry Inhibitors through Dual Myxovirus High-Throughput Screening.

Unlabelled: Influenza A virus (IAV) infections cause major morbidity and mortality, generating an urgent need for novel antiviral therapeutics. We recently established a dual myxovirus high-throughput screening protocol that combines a fully replication-competent IAV-WSN strain and a respiratory syncytial virus reporter strain for the simultaneous identification of IAV-specific, paramyxovirus-specific, and broad-spectrum inhibitors. In the present study, this protocol was applied to a screening campaign to assess a diverse chemical library with over 142,000 entries.

Synthesis of S,S,O-orthoesters and 1,1-difluoroalkyl ethers via reaction of peroxides with lithiated 1,3-dithianes.

Alkyl tetrahydropyranyl peroxides (ROOTHP) transfer alkoxide (OR) to lithiated 1,3-dithianes. The derived S,S,O-orthoesters undergo fluorodesulfurization with HF/pyridine and N-bromosuccinamide (NBS) to furnish difluoromethyl ethers. The overall protocol can be applied to synthesis of both terminal (ROCF2H) and internal (ROCF2R') ethers.

Synthesis of alkyl hydroperoxides via alkylation of gem-dihydroperoxides.

2-Fold alkylation of 1,1-dihydroperoxides, followed by hydrolysis of the resulting bisperoxyacetals, provides a convenient method for synthesis of primary and secondary alkyl hydroperoxides.

Design and optimization of quinazoline derivatives as melanin concentrating hormone receptor 1 (MCHR1) antagonists.

Melanin concentrating hormone (MCH) is an important mediator of energy homeostasis and plays a role in metabolic and CNS disorders. The modeling-supported design, synthesis and multi-parameter optimization (biological activity, solubility, metabolic stability, hERG) of novel quinazoline derivatives as MCHR1 antagonists are described. The in vivo proof of principle for weight loss with a lead compound from this series is exemplified.

Structure-activity relationship studies of novel pyrazole and imidazole carboxamides as cannabinoid-1 (CB1) antagonists.

The synthesis and biological evaluation of novel pyrazole and imidazole carboxamides as CB1 antagonists are described. As a part of eastern amide SAR, various chemically diverse motifs were introduced on rimonabant template. The central pyrazole core was also replaced with its conformationally constrained motif and imidazole moieties.

Novel pyrazole-3-carboxamide derivatives as cannabinoid-1 (CB1) antagonists: journey from non-polar to polar amides.

The synthesis and biological evaluation of novel pyrazole-3-carboxamide derivatives as CB1 antagonists are described. As a part of eastern amide SAR, various chemically diverse motifs were introduced. In general, a range of modifications were well tolerated.