ABSTRACT
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.
Subject(s)
Benzimidazoles/chemical synthesis , Benzimidazoles/pharmacology , Phosphodiesterase Inhibitors/chemical synthesis , Phosphoric Diester Hydrolases/metabolism , Quinazolines/chemical synthesis , Quinazolines/pharmacology , Animals , Benzimidazoles/chemistry , Crystallography, X-Ray , Enzyme Activation/drug effects , Inhibitory Concentration 50 , Models, Molecular , Molecular Structure , Phosphodiesterase Inhibitors/chemistry , Phosphodiesterase Inhibitors/pharmacology , Protein Binding , Quinazolines/chemistry , RatsABSTRACT
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.
Subject(s)
Alcohols/chemistry , Amines/chemistry , Iridium/chemistry , Water/chemistry , Alkylation , CatalysisSubject(s)
Amines/chemistry , Hydrogen/chemistry , Iridium/chemistry , Alkylation , Aniline Compounds/chemistry , CatalysisABSTRACT
Transition-metal-catalyzed hydrogen-transfer reactions have been used for the conversion of alcohols into benzimidazoles and aldehydes into benzoxazoles and benzothiazoles.
Subject(s)
Alcohols/chemistry , Aldehydes/chemistry , Benzimidazoles/chemical synthesis , Benzothiazoles/chemical synthesis , Benzoxazoles/chemical synthesis , Benzimidazoles/chemistry , Benzothiazoles/chemistry , Benzoxazoles/chemistry , Catalysis , Combinatorial Chemistry Techniques , Iridium/chemistry , Molecular Structure , Oxidation-Reduction , Ruthenium/chemistryABSTRACT
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%.
Subject(s)
Alkenes/chemistry , Epoxy Compounds/chemistry , Imines/chemistry , Naphthalenes/chemistry , Azepines/chemistry , Catalysis , Oxidation-Reduction , StereoisomerismABSTRACT
[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.
