Reaction of 4-Bromobenzyl-3-methyl-1,2-oxazin-6-ones with Primary Aliphatic Amines. Synthesis and Structural Determination of New Oxazine and Isoxazole Derivatives

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Aminoimidazo[1,2-a]pyridines: regioselective synthesis of substituted imidazonaphthyridines, azacarbolines and cyclazines

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Auditory cortex interneuron development requires cadherins operating hair-cell mechanoelectrical transduction.

International audienceMany genetic forms of congenital deafness affect the sound reception antenna of cochlear sensory cells, the hair bundle. The resulting sensory deprivation jeopardizes auditory cortex (AC) maturation. Early prosthetic intervention should revive this process. Nevertheless, this view assumes that no intrinsic AC deficits coexist with the cochlear ones, a possibility as yet unexplored. We show here that many GABAergic interneurons, from their generation in the medial ganglionic eminence up to their settlement in the AC, express two cadherin-related (cdhr) proteins, cdhr23 and cdhr15, that form the hair bundle tip links gating the mechanoelectrical transduction channels. Mutant mice lacking either protein showed a major decrease in the number of parvalbumin interneurons specifically in the AC, and displayed audiogenic reflex seizures. Cdhr15- and Cdhr23-expressing interneuron precursors in Cdhr23(-/-) and Cdhr15(-/-) mouse embryos, respectively, failed to enter the embryonic cortex and were scattered throughout the subpallium, consistent with the cell polarity abnormalities we observed in vitro. In the absence of adhesion G protein-coupled receptor V1 (adgrv1), another hair bundle link protein, the entry of Cdhr23- and Cdhr15-expressing interneuron precursors into the embryonic cortex was also impaired. Our results demonstrate that a population of newborn interneurons is endowed with specific cdhr proteins necessary for these cells to reach the developing AC. We suggest that an "early adhesion code" targets populations of interneuron precursors to restricted neocortical regions belonging to the same functional area. These findings open up new perspectives for auditory rehabilitation and cortical therapies in patients

Regioselectivity of 1,3-Dipolar Cycloaddition of 3-Oxidopyridinium Betaines to Olefins and Stereoselective Synthesis of 6-Alkyloxy-5-oxa-9-azatricyclo[5.2.1.04,8]decan-2-one Derivatives

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Development of a freeze-dried kit formulation for the preparation of 99m Tc-NTP 15-5, a radiotracer for scintigraphic imaging of proteoglycans

International audienceThe cartilage-targeting strategy is based on the strong affinity of quaternary ammonium (QA) functions for cartilage proteoglycans. We use a bifunctional agent containing QA moiety and a polyazamacrocycle structure able to complex technetium-99m. (99m)Tc-NTP 15-5 was selected for its high stability and its high affinity for proteoglycans in vivo. Labeling conditions of NTP 15-5 were optimized, and a lyophilized kit was developed for radiolabeling of (99m)Tc-NTP 15-5 (radiochemical yields 94.6±1.8%). (99m)Tc-NTP 15-5 was stable and resulted in favorable biological evaluations

Short and efficient access to imidazo[1,2-a]pyrrolo[3,2-c]pyridine derivatives

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