4-Anilinoquinazoline Derivatives as the First Potent NOD1-RIPK2 Signaling Pathway Inhibitors at the Nanomolar Range.

Inflammation is a defense mechanism that restores tissue damage and eliminates pathogens. Among the pattern recognition receptors that recognize danger or pathogenic signals, nucleotide oligomerization domains 1 and 2 (NOD1/2) have been identified to play an important role in innate immunity responses, and inhibition of NOD1 could be interesting to treat severe infections and inflammatory diseases. In this work, we identified the first selective NOD1 versus NOD2 pathway inhibitors at the nanomolar range based on a 4-anilinoquinazoline scaffold.

One- or Two-Step Synthesis of C-8 and N-9 Substituted Purines.

A novel and original strategy to obtain rapidly a large diversity of C-8 and N-9 substituted purines was developed. The present procedure describes annulation reactions in one or two steps starting from 5-aminoimidazole-4-carbonitriles 1-8 in moderate to good yields. 8,9-Disubstituted-6,9-dihydro-1H-purin-6-ones 9-14, 6-amino-8,9-disubstituted-3,9-dihydro-2H-purin-2-ones 15-20, 8,9-disubstituted-3,9-dihydro-2H-purin-2,6-diamines 21-24 and 6-imino-1-phenyl-8,9-disubstituted-6,9-dihydro-1H-purin-2-(3H)-ones 25-26 were synthesized in one step using formic acid, urea, guanidine carbonate, and phenylisocyanate, respectively, whereas 8,9-disubstituted-9H-purin-6-amines 27-31 and 6-imino-8,9-disubstituted-6,9-dihydro-1H-purin-1-amines 32-33 were obtained in two steps using formamide and hydrazine, respectively.

Repetitive TMS of the temporo-parietal junction disrupts participant's expectations in a spontaneous Theory of Mind task.

A recent debate about Theory of Mind (ToM) concerns whether spontaneous and explicit mentalizing are based on the same mechanisms. However, only a few neuroimaging studies have investigated the neural bases of spontaneous ToM, with inconsistent results. The present study had two goals: first, to investigate whether the right Temporo-Parietal Junction (rTPJ) is crucially involved in spontaneous ToM and second, to gain insight into the role of the rTPJ in ToM.

Chiral separation of new sulfonamide derivatives and evaluation of their enantioselective affinity for human carbonic anhydrase II by microscale thermophoresis and surface plasmon resonance.

The aim of this study was to develop a method combining chiral separation and biophysical techniques to evaluate the enantioselective affinity of original sulfonamide derivatives towards their therapeutic target, the human carbonic anhydrase II (hACII). The first step consisted in the preparation of the enantiomers by chromatographic separation. The performances of HPLC and Supercritical Fluid Chromatography (SFC) were studied at the analytical scale by optimization of various experimental conditions using adsorbed polysaccharide chiral stationary phases (amylose AD-H and cellulose OD-H).

Using Spontaneous Emission of a Qubit as a Resource for Feedback Control.

Persistent control of a transmon qubit is performed by a feedback protocol based on continuous heterodyne measurement of its fluorescence. By driving the qubit and cavity with microwave signals whose amplitudes depend linearly on the instantaneous values of the quadratures of the measured fluorescence field, we show that it is possible to stabilize permanently the qubit in any targeted state. Using a Josephson mixer as a phase-preserving amplifier, it was possible to reach a total measurement efficiency η=35%, leading to a maximum of 59% of excitation and 44% of coherence for the stabilized states.