Use of Aldehyde-Alkyne-Amine Couplings to Generate Medicinal Chemistry-Relevant Linkers.

Copper catalyzed aldehyde-alkyne-amine (A) couplings lead to multifunctional, racemic, propargylic amines, many on a multigram scale. As part of an industrial collaboration, a selection of linkers was purified by chiral HPLC to afford single enantiomers, the absolute configuration of which was determined by vibrational circular dichroism (vCD). To show medicinal chemistry applications, selected linkers were further derivatized into potential cellular probes and (+)-JQ1 containing PROTACs (proteolysis targeting chimeras), which degraded their target protein BRD4.

Non-sedated fast spine magnetic resonance imaging in pediatric patients.

Background: Traditional spine magnetic resonance imaging (MRI) protocols require sedation in young children and uncooperative patients. There is an increased interest in non-sedated pediatric MRI protocols to reduce risks associated with anesthetic agents and improve MRI access.

Objective: To evaluate the image quality of pediatric non-sedated fast spine MRI.

Rethinking chronic toxicity and carcinogenicity assessment for agrochemicals project (ReCAAP): A reporting framework to support a weight of evidence safety assessment without long-term rodent bioassays.

Rodent cancer bioassays have been long-required studies for regulatory assessment of human cancer hazard and risk. These studies use hundreds of animals, are resource intensive, and certain aspects of these studies have limited human relevance. The past 10 years have seen an exponential growth of new technologies with the potential to effectively evaluate human cancer hazard and risk while reducing, refining, or replacing animal use.