Drug Discovery for Soft Drugs on TRPV1 and TRPM8 Channels Using the Passerini Reaction

Multicomponent transformations, such as Ugi and Passerini reactions, allow for the fast synthesis of libraries of medium complexity, avoiding the formation of waste residues and significantly reducing time and money expenditure. Although the Ugi reaction has found a vast number of uses in medicinal chemistry, the employment of the Passerini reaction has received scant attention due to the formation of an \u3b1-acyloxyamide, which hardly resists the hydrolytic enzymes in the body. On the other hand, an overlooked possibility with the Passerini products is to exploit the presence of an ester group in the design and synthesis of soft drugs. We started to fill this gap, designing and synthesizing a series of TRPV1 and TRPM8 agonists able to act as soft drugs by using the Passerini reaction

SHADOWS Technical Proposal

We propose a new proton beam-dump experiment, SHADOWS, to search for a large variety of feebly-interacting particles possibly produced in the interactions of a 400 GeV proton beam with a copper-iron based dump. SHADOWS will use the 400 GeV primary proton beam extracted from the CERN SPS currently serving the NA62 experiment in the CERN North area. SHADOWS will take data off-axis concurrently to the HIKE experiment when the P42 beamline is operated in beam-dump mode and aims to accumulate up to 5 × 10^19 protons on target in about 4 integrated years of operation