Strategies for Accelerating the Development of Catalytic Enantioselective Reactions

The development of enantioselective catalytic processes for the manufacture of chiral intermediates is a very complex endeavor and can be very time consuming and expensive. In this contribution the major issues which might lead to long development times will be discussed and strategies to deal with these problems are described. The general part is illustrated with the approach Solvias has chosen for assisting and supporting the development of enantioselective homogeneous hydrogenation processes, at the moment the most important industrial application of asymmetric catalysis. Special emphasis is given to the application of high-throughput screening (HTS) using a Symyx HiP system and the description of the Solvias portfolio of chiral ligands which makes a broad variety of diphosphine ligands available for all phases of process development from the first screening experiments to the large-scale manufacturing phase. Four case histories serve to illustrate the generic description of the development process

Towards a cancer mission in Horizon Europe: recommendations.

A comprehensive translational cancer research approach focused on personalized and precision medicine, and covering the entire cancer research-care-prevention continuum has the potential to achieve in 2030 a 10-year cancer-specific survival for 75% of patients diagnosed in European Union (EU) member states with a well-developed healthcare system. Concerted actions across this continuum that spans from basic and preclinical research through clinical and prevention research to outcomes research, along with the establishment of interconnected high-quality infrastructures for translational research, clinical and prevention trials and outcomes research, will ensure that science-driven and social innovations benefit patients and individuals at risk across the EU. European infrastructures involving comprehensive cancer centres (CCCs) and CCC-like entities will provide researchers with access to the required critical mass of patients, biological materials and technological resources and can bridge research with healthcare systems. Here, we prioritize research areas to ensure a balanced research portfolio and provide recommendations for achieving key targets. Meeting these targets will require harmonization of EU and national priorities and policies, improved research coordination at the national, regional and EU level and increasingly efficient and flexible funding mechanisms. Long-term support by the EU and commitment of Member States to specialized schemes are also needed for the establishment and sustainability of trans-border infrastructures and networks. In addition to effectively engaging policymakers, all relevant stakeholders within the entire continuum should consensually inform policy through evidence-based advice

6‑Alkoxy-5-aryl-3-pyridinecarboxamides, a New Series of Bioavailable Cannabinoid Receptor Type 1 (CB1) Antagonists Including Peripherally Selective Compounds

We identified 6-alkoxy-5-aryl-3-pyridinecarboxamides as potent CB1 receptor antagonists with high selectivity over CB2 receptors. The series was optimized to reduce lipophilicity compared to rimonabant to achieve peripherally active molecules with minimal central effects. Several compounds that showed high plasma exposures in rats were evaluated in vivo to probe the contribution of central vs peripheral CB1 agonism to metabolic improvement. Both rimonabant and <b>14g</b>, a potent brain penetrant CB1 receptor antagonist, significantly reduced the rate of body weight gain. However, <b>14h</b>, a molecule with markedly reduced brain exposure, had no significant effect on body weight. PK studies confirmed similarly high exposure of both <b>14h</b> and <b>14g</b> in the periphery but 10-fold lower exposure in the brain for <b>14h</b>. On the basis of these data, which are consistent with reported effects in tissue-specific CB1 receptor KO mice, we conclude that the metabolic benefits of CB1 receptor antagonists are primarily centrally mediated as originally believed