Mepolizumab in Patients With Severe Asthma and Comorbidities: 1-Year REALITI-A Analysis.

Background: Severe asthma is complex; comorbidities may influence disease outcomes.

Objective: To assess mepolizumab effectiveness in patients with severe asthma and comorbidities.

Methods: REALITI-A was a 2-year international, prospective study enrolling adults with asthma newly prescribed mepolizumab (100 mg subcutaneously) at physician's discretion.

Reduced need for surgery in severe nasal polyposis with mepolizumab: Randomized trial.

Background: Patients with eosinophilic nasal polyposis frequently require surgery, and recurrence rates are high.

Objective: We sought to assess the efficacy and safety of mepolizumab versus placebo for severe bilateral nasal polyposis.

Methods: This randomized, double-blind, placebo-controlled trial recruited patients aged 18 to 70 years with recurrent nasal polyposis requiring surgery.

Iridium-catalyzed C-H borylation of pyridines.

The iridium-catalysed C-H borylation is a valuable and attractive method for the preparation of aryl and heteroaryl boronates. However, application of this methodology for the preparation of pyridyl and related azinyl boronates can be challenged by low reactivity and propensity for rapid protodeborylation, particularly for a boronate ester ortho to the azinyl nitrogen. Competition experiments have revealed that the low reactivity is due to inhibition of the active catalyst through coordination of the azinyl nitrogen lone pair at the vacant site on the iridium.

A practical drug discovery project at the undergraduate level.

In this article, we describe a practical drug discovery project for third-year undergraduates. No previous knowledge of medicinal chemistry is assumed. Initial lecture workshops cover the basic principles; then students, in teams, seek to improve the profile of a weakly potent, insoluble phosphatidylinositide 3-kinase delta (PI3Kδ) inhibitor (1) through compound array design, molecular modelling, screening data analysis and the synthesis of target compounds in the laboratory.

Ruthenium-catalysed oxidative synthesis of heterocycles from alcohols.

Ruthenium-catalysed hydrogen transfer has been successfully used for the conversion of alcohols into either 2,3-dihydroquinazolines or quinazolines. The choice of reaction conditions allows for the selective formation of either heterocycle and the methodology can also be applied to the sulfonamide analogue.

Borrowing hydrogen methodology for amine synthesis under solvent-free microwave conditions.

Application of microwave heating to the Borrowing Hydrogen strategy to form C-N bonds from alcohols and amines is presented, removing the need for solvent and reducing the reaction times while still yielding results comparable with those using thermal heating.

"One-pot" tandem C-H borylation/1,4-conjugate addition/reduction sequence.

A microwave-assisted, one-pot, iridium-catalyzed aromatic C-H borylation/rhodium-catalyzed 1,4-conjugate addition sequence provides a highly robust protocol suitable for high-throughput array synthesis. Selective formation of either β-aryl-substituted ketones or the corresponding alcohols can be achieved in good overall yields by simple variation of the reaction conditions.

Ruthenium-catalyzed aromatic C-H activation of benzylic alcohols via remote electronic activation.

Remote electronic activation of benzylic alcohols via temporary oxidation facilitates ruthenium-catalyzed arene C-H activation for a range of aromatic alcohols.

Ruthenium-catalyzed oxidation of alcohols into amides.

The synthesis of secondary amides from primary alcohols and amines has been developed using commercially available [Ru(p-cymene)Cl(2)](2) with bis(diphenylphosphino)butane (dppb) as the catalyst.

Ruthenium-catalyzed N-alkylation of amines and sulfonamides using borrowing hydrogen methodology.

The alkylation of amines by alcohols has been achieved using 0.5 mol % [Ru(p-cymene)Cl(2)](2) with the bidentate phosphines dppf or DPEphos as the catalyst. Primary amines have been converted into secondary amines, and secondary amines into tertiary amines, including the syntheses of Piribedil, Tripelennamine, and Chlorpheniramine.

Electronically varied quinazolinaps for asymmetric catalysis.

The synthesis and resolution of electronically varied axially chiral Quinazolinaps is reported. These ligands bear different aryl groups on the donor phosphorus atom and were synthesised as part of our investigations into electronic effects within this ligand class. A diastereomerically pure palladacycle of one ligand was characterised by X-ray crystallography.