Sanofi-Aventis Ltd.

Dengue endemicity varies but comparative, multicountry data are extremely limited. An improved understanding is needed to prioritize prevention, including vaccination, which is currently recommended only under specific epidemiol. conditions. We used serol. study data from 46 geog. sites in 13 countries to estimate dengue force of infection (FOI, the proportion of children seroconverting per yr) under assumptions of either age-constant or age-varying FOI, and the age at which 50% and 80% of children had been infected. After exclusions, 13 661 subjects were included. Estimated constant FOI varied widely, from 1.7% (Singapore) to 24.1% (the Philippines). In the site-level anal. 44 sites (96%) reached 50% seroconversion and 35 sites (75%) reached 80% seroconversion by age 18 years, with significant heterogeneity. These findings confirm that children living in dengue-endemic countries receive intense early dengue exposure, increasing risk of secondary infection, and imply serosurveys at fine spatial resolutions are needed to inform vaccination campaigns.

Deuterated drugs have seen a continuous interest in pharmaceutical industry. While the gold-rush mood from the early 21^th century has faded a bit, there is a proven evidence that the substitution of hydrogen by its isotope deuterium can have a significant pos. effect for patients. With the first deuterated drugs on the market and further ones in clin. trials the need for the development of convenient deuteration methods became evident. The possible applications reach from small milligram reactions for medicinal chem. optimization to large industrial batches with tons of material in process chem. All these efforts combine the need for cost-efficient, easy to handle and selective deuteration reactions. One approach to fulfill all these criteria can be the late stage deuteration reaction of complex mols. Late stage deuterations follow the concept of the Hydrogen Isotope Exchange (HIE) reactions, which are considered as the most fundamental of all C-H functionalization's. In the presentation an overview and perspective of the most convenient late stage deuteration methods is given and discussed.

The two isotopomers of teriflunomide were synthesized starting from isotopically stable-labeled stocks of [¹³ C]potassium cyanide and [1-¹³ C]ethyl bromoacetate. The two ¹³ C-labeled compounds 1a, b were applied in several NMR studies to study the E/Z ratio in different matrices. In a solution, such as dimethyl sulfoxide (DMSO), a dynamic equilibrium between E/Z-isomers (ratio of 8:92) was determined by initial ¹³ C-carbon NMR experiments. To get insights into the E/Z ratio of teriflunomide under in vivo conditions, advanced heteronuclear NMR (heteronuclear Overhauser effect spectroscopy [HOESY]) in D₂ O and mixtures of D₂ O/plasma were performed. Whereas NMR experiments in mixtures of water and plasma failed owing to extreme line broadening, NMR spectra in water at pH 7.4 showed only the Z-isomer.