Enantiomerically Pure [2.2]Paracyclophane-4-thiol: A Planar Chiral Sulfur-Based Building Block Readily Available by Resolution with an Amino Acid Chiral Auxiliary

Acyl chloride of N-phthaloyl-(S)-isoleucine is an efficient chiral auxiliary for the resolution of (+/-)-[2.2]paracyclophane-4-thiol. A preparative protocol, based on the conversion into diastereoisomeric thiolesters and separation by two fractional crystallizations and column chromatography, was developed. Deprotection with LiAlH4 allowed isolation of the individual thiol enantiomers in good yield (similar to 40%) and high enantiomeric purity (ee >93%). The absolute configurations were determined by comparison of the optical rotation value of the products with literature data and were confirmed by X-ray crystallography

Catalytic reductive N-alkylation of amines using carboxylic acids

We report a catalytic reductive alkylation reaction of primary or secondary amines with carboxylic acids. The two-phase process involves silane mediated direct amidation followed by catalytic reduction

A supervised adverse drug reaction signalling framework imitating Bradford Hill’s causality considerations

Big longitudinal observational medical data potentially hold a wealth of information and have been recognised as potential sources for gaining new drug safety knowledge. Unfortunately there are many complexities and underlying issues when analysing longitudinal observational data. Due to these complexities, existing methods for large-scale detection of negative side effects using observational data all tend to have issues distinguishing between association and causality. New methods that can better discriminate causal and non-causal relationships need to be developed to fully utilise the data. In this paper we propose using a set of causality considerations developed by the epidemiologist Bradford Hill as a basis for engineering features that enable the application of supervised learning for the problem of detecting negative side effects. The Bradford Hill considerations look at various perspectives of a drug and outcome relationship to determine whether it shows causal traits. We taught a classifier to find patterns within these perspectives and it learned to discriminate between association and causality. The novelty of this research is the combination of supervised learning and Bradford Hill’s causality considerations to automate the Bradford Hill’s causality assessment. We evaluated the framework on a drug safety gold standard known as the observational medical outcomes partnership’s non-specified association reference set. The methodology obtained excellent discrimination ability with area under the curves ranging between 0.792 and 0.940 (existing method optimal: 0.73) and a mean average precision of 0.640 (existing method optimal: 0.141). The proposed features can be calculated efficiently and be readily updated, making the framework suitable for big observational data

Fluorine-18 in radiochemistry and PET imaging

LDM-TEPInternational audienc

Comment la chimie fait progresser l’imagerie médicale

LDM TEPNational audienc

[18F]FLUSONIM : un nouveau radiotraceur pour l’imagerie TEP de l’hypoxie à fort contraste et délai ultra-court

LDM-TEPNational audienc

Développement de nouveaux radiopharmaceutiques/ radiotraceurs marqués au fluor-18 et évaluations précliniques

LDM TEPNational audienc

Radiochemistry with fluorine-18 for hypoxia PET imaging

LDM-TEPInternational audienc

Radiomarquage au fluor-18 de biopolymères pour l’imagerie TEP

LDM-TEPNational audienc