Triazoloquinazolines as a novel class of phosphodiesterase 10A (PDE10A) inhibitors.

Novel triazoloquinazolines have been found as phosphodiesterase 10A (PDE10A) inhibitors. Structure-activity studies improved the initial micromolar potency which was found in the lead compound by a 100-fold identifying 5-(1H-benzoimidazol-2-ylmethylsulfanyl)-2-methyl-[1,2,4]triazolo[1,5-c]quinazoline, 42 (PDE10A IC(50)=12 nM) as the most potent compound from the series. Two X-ray structures revealed novel binding modes to the catalytic site of the PDE10A enzyme.

Iridium-catalysed amine alkylation with alcohols in water.

Amines have been directly alkylated with alcohols using 1 mol% [Cp*IrI(2)](2) catalyst in water in the absence of base or other additives.

Synthesis of benzazoles by hydrogen-transfer catalysis.

Transition-metal-catalyzed hydrogen-transfer reactions have been used for the conversion of alcohols into benzimidazoles and aldehydes into benzoxazoles and benzothiazoles.

New chiral binaphthalene-derived iminium salt organocatalysts for asymmetric epoxidation of alkenes.

A series of binaphthalene-fused azepinium salts has been generated and used as organocatalysts in the asymmetric epoxidation of unfunctionalized alkenes, giving rise to ees of up to 84%.

Aminolysis of resin-bound N-nosylaziridine-2-carboxylic acids.

[Structure: see text] Solid-phase synthesis is a rapidly developing area of organic chemistry, of particular importance for medicinal chemistry and chemical biology. Aziridines have previously only rarely been applied in solid-phase synthesis. In the present work, aminolysis of resin-bound, spring-loaded N-nitrobenzenesulfonyl-activated aziridine-2-carboxylic acids has been optimized and employed in the synthesis of a number of open-chain and heterocyclic scaffolds, including enantiopure products.