Contilisant+Tubastatin A Hybrids: Polyfunctionalized Indole Derivatives as New HDAC Inhibitor-Based Multitarget Small Molecules with and Activity in Neurodegenerative Diseases.

Herein, we describe the design, synthesis, and biological evaluation of 15 + hybrids. These ligands are polyfunctionalized indole derivatives developed by juxtaposing selected pharmacophoric moieties of and to act as multifunctional ligands. Compounds and were identified as potent HDAC6 inhibitors (IC = 0.

Precursors consumption preferences and thiol release capacity of the wine yeasts Saccharomyces cerevisiae, Torulaspora delbrueckii, and Lachancea thermotolerans.

The aromatic profile of wine determines its overall final quality, and among the volatile molecules that define it, varietal thiols are responsible for shaping the distinctive character of certain wine varieties. In grape must, these thiols are conjugated to amino acids or small peptides in a non-volatile form. During wine fermentation, yeasts play a principal role in expressing these aromatic compounds as they internalise and cleavage these precursors, releasing the corresponding free and aroma-impacting fraction.

Expanding the Chemical Space of 1,2-Difunctionalized Cyclobutanes.

An efficient approach to the synthesis of previously unavailable or hardly accessible 1,2-difunctionalized cyclobutanes (mostly with NH/NHBoc, OH, SH, or SOF groups attached to the carbocycle either directly or via a CH unit) relying on the divergent strategy is described. This class of compounds provides -enriched and conformationally restricted building blocks that are of special demand for medicinal chemistry. The target compounds were prepared not only as pure racemic (±)-- and (±)--diastereomers but in some cases also as single enantiomers.

Expanding the chemical space of 3(5)-functionalized 1,2,4-triazoles.

Unlabelled: An efficient approach to the gram-scale synthesis of 3(5)-substituted, 1,3- and 1,5-disubstituted 1,2,4-triazole-derived building blocks is described. The key synthetic precursors - 1,2,4-triazole-3(5)-carboxylates (20 examples, 35-89% yield) were prepared from readily available acyl hydrazides and ethyl 2-ethoxy-2-iminoacetate hydrochloride. Further transformations were performed following the convergent synthetic strategy and allowed the preparation of 1,3- and 1,5-disubstituted 1,2,4-triazole-derived esters (16 examples, 25-75% yield), 3(5)-substituted, 1,3- and 1,5-disubstituted carboxylate salts (18 examples, 78-93% yield), amides (5 examples, 82-93% yield), nitriles (5 examples, 30-85% yield), hydrazides (6 examples, 84-89% yield), and hydroxamic acids (3 examples, 73-78% yield).